Adaptogen Extracts

Herbal adaptogens concentrating active compounds while maintaining complex synergistic co-factors – supporting Adrenal/ HPA regulation, Long Term Potentiation, AMPK activation, neurogenesis, catecholamine production, tissue regeneration, and many regulatory functions.

EnXtra® Alpinia Galanga

ALPINIA GALANGA COMMON NAME

Greater Galangal | Thai Ginger | Siamese Ginger

TOP BENEFITS OF ALPINIA GALANGA

  • Sharpens alertness and focus*
  • Amplifies caffeine’s nootropic benefits*
  • Supports brain and cognitive function*

WHAT IS ALPINIA GALANGA?

Alpinia galanga is native to Southeast Asia, where it’s used as a food and herb.[1]. It is part of the ginger family, and, similar to ginger, the rhizome, or creeping rootstalk is what’s used. The rhizome has a pungent smell reminiscent of black pepper and pine. The similarity in appearance to the ginger rhizome has led to one of its common names, Thai ginger. In some traditional medical systems, it is regarded as being superior to ginger. EnXtra® is a clinically studied and standardized Alpinia galanga rhizome extract. In humans studies, EnXtra® has been synergistic with caffeine. In a clinical study, supplementation with EnXtra® supported alertness and focus It’s clinically proven to improve alertness and focus for up to 5 hours with and without caffeine. EnXtra® can be used as a replacement for caffeine or used with caffeine to prevent crash and prolong caffeine’s nootropic benefits.[2]

NEUROHACKER’S ALPINIA GALANGA SOURCING

EnXtra® has been used in human clinical studies, where it has enhanced alertness and focus, and amplified the nootropic response to caffeine.

EnXtra® is created by Enovate Biolife, and is standardized for total polyphenols (not less than [NLT] 3%), flavanoids (NLT 4%), polysaccharides (NLT 20%) and pyrocatecollic type tannins (NLT 1%). 

EnXtra® is responsibly sourced. It is cultivated without pesticides in hilly terrain and hand picked to ensure optimum potency. It is DNA authenticated to ensure botanical identification.

EnXtra® is GRAS affirmed, non-GMO, gluten-free, vegan, Kosher certified and Halal compliant.

Grown in India.

EnXtra® is a registered trademark of Enovate Bioscience. 

ALPINIA GALANGA DOSING PRINCIPLES AND RATIONALE

We consider Alpinia galanga to be in the adaptogenic herb category; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is consistent with the studied amount in the human clinical studies.*

ALPINIA GALANGA KEY MECHANISMS

Cognitive function

  • Supports mental alertness [2]
  • Supports attention [3]
  • Supports memory [4,5]

Brain function

  • Neuroprotective effects [4–6]
  • CNS stimulant activity [7]
  • Supports locomotor activity and motor coordination [7]
  • Downregulates acetylcholinesterase (AChE) levels/activity in the brain [4,5]
  • Downregulates monoamine oxidase (MAO) A and B levels/activity in the brain [5]

Antioxidant defenses

  • Upregulates antioxidant enzymes in the brain (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [4–6,8]
  • Replenishes glutathione (GSH) levels [8]
  • Downregulates lipid peroxidation [6,8]

Other effects

  • Supports healthy cardiometabolic parameters [8,9]
  • Immunostimulant activity [10]

 Synergies

  • Caffeine — supports sustained attention [2]


REFERENCES 

[1]D. Kaushik, J. Yadav, P. Kaushik, D. Sacher, R. Rani, Zhong Xi Yi Jie He Xue Bao 9 (2011) 1061–1065.
[2]S. Srivastava, M. Mennemeier, S. Pimple, J. Am. Coll. Nutr. 36 (2017) 631–639.
[3]S. Shalini Srivastava, BAOJN 3 (2017) 1–10.
[4]J.C. Hanish Singh, V. Alagarsamy, P.V. Diwan, S. Sathesh Kumar, J.C. Nisha, Y. Narsimha Reddy, J. Ethnopharmacol. 138 (2011) 85–91.
[5]J.C. Hanish Singh, V. Alagarsamy, S. Sathesh Kumar, Y. Narsimha Reddy, Phytother. Res. 25 (2011) 1061–1067.
[6]R. Mundugaru, S. Sivanesan, P. Udaykumar, V. Dj, S.N. Prabhu, B. Ravishankar, IJPER 52 (2018) s77–s85.
[7]S. Saha, S. Banerjee, Indian J. Exp. Biol. 51 (2013) 828–832.
[8]P. Kaushik, D. Kaushik, J. Yadav, P. Pahwa, Pak. J. Biol. Sci. 16 (2013) 804–811.
[9]R.K. Verma, G. Mishra, P. Singh, K.K. Jha, R.L. Khosa, Ayu 36 (2015) 91–95.
[10]D. Bendjeddou, K. Lalaoui, D. Satta, J. Ethnopharmacol. 88 (2003) 155–160.

White Peony (Paeonia lactiflora) Root Extract

WHITE PEONY COMMON NAME

White Peony | Chinese Peony | Radix Paeoniae Alba | Bai Shao

TOP BENEFITS OF WHITE PEONY

Supports mood*
Support brain function*
Supports sleep

WHAT IS WHITE PEONY?

The peeled roots of white peony (Peonia lactiflora) are one of the most common herbs used in Traditional Chinese Medicine, where some of its uses included supporting sleep, emotional stability, mental focus, and immunity. It is one of the four herbs in a TCM herbal formula called Si Ni San, which is used to support sleep quality and help with mental fatigue. White peony root contains a compound called paeoniflorin [1] that in preclinical research influences adenosine signaling—a molecule involved in the sleep homeostatic drive. Preclinical research has also reported that paeoniflorin supports brain protection and repair processes and molecules (such as BDNF and NGF), counters chronic stress, influences learning, and promotes a balanced mood.*

NEUROHACKER’S WHITE PEONY SOURCING

White peony root extract is standardized to contain not less than 10% paeoniflorin, since this compound is the most researched of white peony root’s unique compounds and is used as the marker compound for standardization. 

White peony root extract is Non-GMO and Vegan.

WHITE PEONY DOSING PRINCIPLES AND RATIONALE

One of our dosing principles is to determine whether there is a dosing range, in which many of the benefits occur and above which there appears to be diminishing returns (i.e., a threshold), and to provide a dose within this threshold range (see Neurohacker Dosing Principles). We consider the amount of paeoniflorin in a white peony root extract to be the critical factor when determining the dose of an extract to use. Only low-to-moderate amounts of white peony are typically needed when paeoniflorin content is more concentrated.

WHITE PEONY KEY MECHANISMS

Stress

Supports healthy behavioral and physiological responses to stress [2–10]

Supports stress hormone levels [5,10,11]

Brain function

Supports learning and memory [8]

Supports sleep [12–14]

Supports adenosine signaling [12,13,15,16]

Supports acetylcholine signaling [17]

Supports serotonin levels [3,5,10]

Supports brain-derived neurotrophic factor (BDNF) [4,8,9,18]

Supports brain mitochondrial structure and function [19]

Supports hippocampal synaptic density [8,19]

Supports brain insulin signaling [19,20]

Modulates glycogen synthase kinase 3β (GSK3β) activity [20,21]

Supports cerebral blood flow [22]

Supports neuroprotective functions [15–17,19–25]

Supports brain mitochondrial function [19]

Supports brain autophagy [26]

Gut microbiota

Supports the composition of the gut microbiota [2]


REFERENCES

[1] X. Zhang, Y. Zhai, J. Yuan, Y. Hu, New insights into Paeoniaceae used as medicinal plants in China, Sci. Rep. 9 (2019) 18469.

[2] J.-B. Yu, Z.-X. Zhao, R. Peng, L.-B. Pan, J. Fu, S.-R. Ma, P. Han, L. Cong, Z.-W. Zhang, L.-X. Sun, J.-D. Jiang, Y. Wang, Gut Microbiota-Based Pharmacokinetics and the Antidepressant Mechanism of Paeoniflorin, Front. Pharmacol. 10 (2019) 268.

[3] F. Qiu, X. Zhong, Q. Mao, Z. Huang, The antidepressant-like effects of paeoniflorin in mouse models, Exp. Ther. Med. 5 (2013) 1113–1116.

[4] M.-Z. Hu, A.-R. Wang, Z.-Y. Zhao, X.-Y. Chen, Y.-B. Li, B. Liu, Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model, Neurol. Res. 41 (2019) 446–455.

[5] F.-M. Qiu, X.-M. Zhong, Q.-Q. Mao, Z. Huang, Antidepressant-like effects of paeoniflorin on the behavioural, biochemical, and neurochemical patterns of rats exposed to chronic unpredictable stress, Neurosci. Lett. 541 (2013) 209–213.

[6] J. Li, S. Huang, W. Huang, W. Wang, G. Wen, L. Gao, X. Fu, M. Wang, W. Liang, H.Y. Kwan, X. Zhao, Z. Lv, Paeoniflorin ameliorates interferon-alpha-induced neuroinflammation and depressive-like behaviors in mice, Oncotarget. 8 (2017) 8264–8282.

[7] S. Wang, X. Zhao, Z. Qiao, X. Jia, Y. Qi, Paeoniflorin attenuates depressive behaviors in systemic lupus erythematosus mice, Biomed. Pharmacother. 103 (2018) 248–252.

[8] S.-C. Liu, W.-Y. Hu, W.-Y. Zhang, L. Yang, Y. Li, Z.-C. Xiao, M. Zhang, Z.-Y. He, Paeoniflorin attenuates impairment of spatial learning and hippocampal long-term potentiation in mice subjected to chronic unpredictable mild stress, Psychopharmacology . 236 (2019) 2823–2834.

[9] L.-B. Chen, F.-M. Qiu, X.-M. Zhong, C. Hong, Z. Huang, Promoting neurogenesis in hippocampal dentate gyrus of chronic unpredictable stress-induced depressive-like rats with paeoniflorin, J. Integr. Neurosci. 18 (2019) 43–49.

[10]Z.-K. Qiu, J.-L. He, X. Liu, J. Zeng, W. Xiao, Q.-H. Fan, X.-M. Chai, W.-H. Ye, J.-S. Chen, Anxiolytic-like effects of paeoniflorin in an animal model of post traumatic stress disorder, Metab. Brain Dis. 33 (2018) 1175–1185.

[11] H. Huang, J. Zhao, L. Jiang, Y. Xie, Y. Xia, R. Lv, L. Dong, Paeoniflorin improves menopause depression in ovariectomized rats under chronic unpredictable mild stress, Int. J. Clin. Exp. Med. 8 (2015) 5103–5111.

[12] D. Yin, Y.-Y. Liu, T.-X. Wang, Z.-Z. Hu, W.-M. Qu, J.-F. Chen, N.-N. Cheng, Z.-L. Huang, Paeoniflorin exerts analgesic and hypnotic effects via adenosine A1 receptors in a mouse neuropathic pain model, Psychopharmacology . 233 (2016) 281–293.

[13] C.-R. Chen, Y. Sun, Y.-J. Luo, X. Zhao, J.-F. Chen, Y. Yanagawa, W.-M. Qu, Z.-L. Huang, Paeoniflorin Promotes Non-rapid Eye Movement Sleep via Adenosine A1 Receptors, J. Pharmacol. Exp. Ther. 356 (2016) 64–73.

[14] Y. Li, P. Wu, Y. Ning, X. Yan, T. Zhu, C. Ma, A. Liu, Sedative and hypnotic effect of freeze-dried paeoniflorin and sini san freeze-dried powder in pentobarbital sodium-induced mice, J. Tradit. Chin. Med. 34 (2014) 184–187.

[15] D.-Z. Liu, K.-Q. Xie, X.-Q. Ji, Y. Ye, C.-L. Jiang, X.-Z. Zhu, Neuroprotective effect of paeoniflorin on cerebral ischemic rat by activating adenosine A1 receptor in a manner different from its classical agonists, Br. J. Pharmacol. 146 (2005) 604–611.

[16] H.-Q. Liu, W.-Y. Zhang, X.-T. Luo, Y. Ye, X.-Z. Zhu, Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease by activation of adenosine A1 receptor, Br. J. Pharmacol. 148 (2006) 314–325.

[17] C.-H. Ko, C.-P. Huang, Y.-W. Lin, C.-L. Hsieh, Paeoniflorin has anti-inflammation and neurogenesis functions through nicotinic acetylcholine receptors in cerebral ischemia-reperfusion injury rats, Iran. J. Basic Med. Sci. 21 (2018) 1174–1178.

[18] Y. Zhang, L.-L. Wang, Y. Wu, N. Wang, S.-M. Wang, B. Zhang, C.-G. Shi, S.-C. Zhang, Paeoniflorin attenuates hippocampal damage in a rat model of vascular dementia, Exp. Ther. Med. 12 (2016) 3729–3734.

[19] D. Wang, L. Liu, S. Li, C. Wang, Effects of paeoniflorin on neurobehavior, oxidative stress, brain insulin signaling, and synaptic alterations in intracerebroventricular streptozotocin-induced cognitive impairment in mice, Physiol. Behav. 191 (2018) 12–20.

[20] X. Sun, S. Li, L. Xu, H. Wang, Z. Ma, Q. Fu, R. Qu, S. Ma, Paeoniflorin ameliorates cognitive dysfunction via regulating SOCS2/IRS-1 pathway in diabetic rats, Physiol. Behav. 174 (2017) 162–169.

[21] H.-R. Zhang, J.-H. Peng, X.-B. Cheng, B.-Z. Shi, M.-Y. Zhang, R.-X. Xu, Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer’s Disease, Neurochem. Res. 40 (2015) 1583–1592.

[22] L.-G. Zhang, L.-J. Wang, Q.-Q. Shen, H.-F. Wang, Y. Zhang, C.-G. Shi, S.-C. Zhang, M.-Y. Zhang, Paeoniflorin improves regional cerebral blood flow and suppresses inflammatory factors in the hippocampus of rats with vascular dementia, Chin. J. Integr. Med. 23 (2017) 696–702.

[23] X.-Q. Luo, A. Li, X. Yang, X. Xiao, R. Hu, T.-W. Wang, X.-Y. Dou, D.-J. Yang, Z. Dong, Paeoniflorin exerts neuroprotective effects by modulating the M1/M2 subset polarization of microglia/macrophages in the hippocampal CA1 region of vascular dementia rats via cannabinoid receptor 2, Chin. Med. 13 (2018) 14.

[24] X. Gu, Z. Cai, M. Cai, K. Liu, D. Liu, Q. Zhang, J. Tan, Q. Ma, Protective effect of paeoniflorin on inflammation and apoptosis in the cerebral cortex of a transgenic mouse model of Alzheimer’s disease, Mol. Med. Rep. 13 (2016) 2247–2252.

[25] J. Liu, D.-Z. Jin, L. Xiao, X.-Z. Zhu, Paeoniflorin attenuates chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rats, Brain Res. 1089 (2006) 162–170.

[26] X.-S. Gu, F. Wang, C.-Y. Zhang, C.-J. Mao, J. Yang, Y.-P. Yang, S. Liu, L.-F. Hu, C.-F. Liu, Neuroprotective Effects of Paeoniflorin on 6-OHDA-Lesioned Rat Model of Parkinson’s Disease, Neurochem. Res. 41 (2016) 2923–2936.

Sensoril® Ashwagandha Withania somnifera Root and Leaf Extract

Withania somnifera Common Name

Ashwagandha | Indian ginseng

Top Benefits of Withania somnifera

  • Supports healthy aging* 
  • Supports energy*
  • Supports a healthy stress response*
  • Supports exercise performance*
  • Supports healthy weight* 
  • Supports healthy metabolism*  
  • Supports mitochondrial structure and function* 
  • Supports antioxidant defenses* 
  • Supports brain function and mental cognition* 
  • Supports thyroid function*  
  • Supports healthy joint function*
  • Supports blood sugar balance*
  • Supports sleep*

What is Withania somnifera?

Ashwagandha is an Ayurvedic herb with adaptogenic properties—it’s often referred to as “Indian ginseng.” Ashwagandha has a long history of use and has been reported to have several health-promoting effects, supporting healthy energy, metabolism, stress response, physical performance, sleep, joint health, and cognitive performance. The novel active constituents are a group of plant compounds called withanolide glycosides. Sensoril® root and leaf extract is standardized for withanolide glycoside content.

Neurohacker’s Withania somnifera Sourcing

Sensoril® has been clinically tested in 10 randomized, double-blind, placebo-controlled human trials.

Created by Natreon Inc., a leader in scientifically studied and tested Ayurvedic ingredients.

Leaf and root extract triple standardized to contain a minimum of 10% withanolide glycosides, the main bioactive; a minimum of 32% oligosaccharides, which increase the bioavailability of the withanolide glycosides; and a maximum of 0.5% free withanolides (as Withaferin A).

Protected by multiple U.S. patents with self-affirmed generally recognized as safe (GRAS) status). 

Vegetarian ● Organic compliant or certified organic ● Non-GMO Allergen & Gluten-free ● Kosher & Halal certified

Withania somnifera Dosing Principles and Rationale

We consider Ashwagandha to be an herbal adaptogen, so expect it to follow hormetic dosing principles (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. So, it’s important to identify the lowest dose that can produce the desired response. Sensoril®—the standardized extract we use—produced a threshold  response in a study that gave different daily dosages—125 mg, 250 mg, 500 mg. Effect size was slightly greater for the higher doses, but most of the change was evident with the lowest dose. 1 We opted for this lower dose to be consistent with a core hormetic principle—only do or use as much as something as would be needed to stimulate the desired response.

Withania somnifera Key Mechanisms 

Mitochondrial structure and function

  • Supports mitochondrial membrane potential and structural integrity[2]
  • Protects from mitochondrial damage[2]
  • Protects from mitochondrial membrane permeabilization[3]
  • Protects from complex I-V Inhibition (protects electron transport chain and oxidative phosphorylation performance)[2,4–6]
  • Upregulates citric acid cycle enzymes[6]

Improves exercise performance (ergogenic effect)

  • Supports endurance performance[7,8]
  • Supports muscle strength[9,10]
  • Supports post-exercise recovery[10]

Metabolism

  • Supports healthy insulin sensitivity[11–15]
  • Supports healthy blood glucose levels[12–16]
  • Supports healthy leptin signaling[11,15]

Body weight 

  • Supports healthy body weight[11,15]
  • Supports healthy feeding behaviors[11,17]
  • Upregulates lean mass[10]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx])[2,4,5,16,18]
  • Replenishes glutathione (GSH) levels[2,4,16]
  • Downregulates oxidative stress and reactive oxygen species levels[2–4,19]

Cellular signaling 

  • Downregulates the expression of proinflammatory cytokines – tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), and IL-6[11–13]

Brain function

  • Supports cognitive and psychomotor performance[20,21]
  • Supports memory, executive function, attention, and information processing speed[22]
  • Neuroprotective – protects from neuronal mitochondrial swelling and apoptosis; protects cognitive function (ischemia, oxidative stress)[2]
  • Protects from neurotoxicity[4,5]
  • Downregulates the basal activity levels of acetylcholine esterase[4]
  • Upregulates dopamine levels[4]
  • Supports mood[11]
  • Regulates neural cytokine signaling[11]
  • Supports quality of sleep[9]

Thyroid function

  • Supports thyroid function[23–25]

Stress response

  • Supports stress management[1,17,26]
  • Downregulates serum cortisol levels[1,17,26]
  • Downregulates endoplasmic reticulum (ER) stress[15]

Healthy aging and longevity 

  • Lifespan extension effects (Caenorhabditis elegans)[19,27]
  • Upregulates insulin-like growth factor-1 (IGF-1) signaling pathway[19,27]
  • Downregulates α-synuclein and amyloid-β aggregation[19]
  • Upregulates FOXO3A and SIRT3[28]


REFERENCES

[1] Auddy B, et al. Journal of American Nutraceutical Association. 2008;11:50-56.
[2] Sood A, et al. Metab Brain Dis. 2018;33(4):1261-1274. doi:10.1007/s11011-018-0234-2
[3] Parihar P, et al. Cell Mol Biol . 2016;62(1):73-83. PMID: 26828992.
[4] Manjunath MJ, Muralidhara. J Food Sci Technol. 2015;52(4):1971-1981. doi:10.1007/s13197-013-1219-0
[5] Kumar P, Kumar A. J Med Food. 2009;12(3):591-600. doi:10.1089/jmf.2008.0028
[6] Senthilnathan P, et al. Life Sci. 2006;78(9):1010-1014. doi:10.1016/j.lfs.2005.06.005
[7] Sandhu JS, et al. Int J Ayurveda Res. 2010;1(3):144-149. doi:10.4103/0974-7788.72485
[8] Choudhary B, et al. Ayu. 2015;36(1):63-68. doi:10.4103/0974-8520.169002
[9] Raut AA, et al. J Ayurveda Integr Med. 2012;3(3):111-114. doi:10.4103/0975-9476.100168
[10] Wankhede S, et al. J Int Soc Sports Nutr. 2015;12:43. doi:10.1186/s12970-015-0104-9
[11] Kaur T, Kaur G. J Neuroinflammation. 2017;14(1):201. doi:10.1186/s12974-017-0975-6
[12] Shahraki MR, et al. J Basic Clin Physiol Pharmacol. 2016;27(4):387-391. doi:10.1515/jbcpp-2015-0053
[13] Samadi Noshahr Z, et al. Rep Biochem Mol Biol. 2015;3(2):62-67. PMID: 26989739.
[14] Anwer T, et al. Basic Clin Pharmacol Toxicol. 2008;102(6):498-503. doi:10.1111/j.1742-7843.2008.00223.x
[15] Lee J, et al. Nat Med. 2016;22(9):1023-1032. doi:10.1038/nm.4145
[16] Anwer T, et al. Acta Pol Pharm. 2012;69(6):1095-1101. PMID: 23285670.
[17] Choudhary D, et al. J Evid Based Complem Altern Med. 2017;22(1):96-106. doi:10.1177/2156587216641830
[18] Gupta SK, et al. Drug Metabol Drug Interact. 2003;19(3):211-222. PMID: 14682611.
[19] Akhoon BA, et al. Exp Gerontol. 2016;78:47-56. doi:10.1016/j.exger.2016.03.004
[20] Pingali U, et al. Pharmacognosy Res. 2014;6(1):12-18. doi:10.4103/0974-8490.122912
[21] Chengappa KNR, et al. J Clin Psychiatry. 2013;74(11):1076-1083. doi:10.4088/JCP.13m08413
[22] Choudhary D, et al. J Diet Suppl. 2017;14(6):599-612. doi:10.1080/19390211.2017.1284970
[23] Sharma AK, et al. J Altern Complement Med. 2018;24(3):243-248. doi:10.1089/acm.2017.0183
[24] Gannon JM, et al. J Ayurveda Integr Med. 2014;5(4):241-245. doi:10.4103/0975-9476.146566
[25] Jatwa R, Kar A. Phytother Res. 2009;23(8):1140-1145. doi:10.1002/ptr.2765
[26] Chandrasekhar K, et al. Indian J Psychol Med. 2012;34(3):255-262. doi:10.4103/0253-7176.106022
[27] Akhoon BA, et al. Exp Gerontol. 2018;104:113-117. doi:10.1016/j.exger.2018.02.004
[28] Pradhan R, et al. Exp Gerontol. 2017;95:9-15. doi:10.1016/j.exger.2017.05.013

Gynostemma pentaphyllum

Gynostemma pentaphyllum Common Name

Gynostemma | Southern Ginseng | Jiaogulan

Top Benefits of Gynostemma pentaphyllum

  • Supports healthy weight*
  • Supports metabolism*
  • Supports exercise performance*
  • Supports mitochondrial structure and function*
  • Supports cellular responses and antioxidant defenses*
  • Supports brain health*
  • Support cardiovascular health*
  • Supports kidney health*
  • Supports liver health*
  • Supports gastrointestinal health*
  • Supports healthy gut microbiota*

What is Gynostemma pentaphyllum?

Gynostemma pentaphyllum (Southern Ginseng) is an herb given Ginseng status although not related to Panax Ginseng. Until recently it was a locally-known herb used primarily in mountainous regions of southern China and in northern Vietnam. It is described by the local inhabitants as the "immortality herb,” because people within Guizhou Province, where jiaogulan herbal teas are consumed regularly, are said to have a history of unusual longevity. 

Neurohacker’s Gynostemma pentaphyllum Sourcing

A Gynostemma pentaphyllum extract was selected to be standardized to contain 98% gypenosides.

We opted for a standardized extract for two reasons. Gypenosides are thought to be responsible for much of this herb’s functional benefits. And they have been the primary focus of the majority of the research on this plant.

Studies of this extract suggest it supports cellular and metabolic adaptations similar to what might be expected with exercise. *

Gynostemma pentaphyllum Dosing Principles and Rationale

We consider Gynostemma pentaphyllum to be an herbal adaptogen, which would follow hormetic dosing principles (see Neurohacker Dosing Principles). It contains a category of triterpenoid saponin compounds called gypenosides. These share many structural and functional similarities with the ginsenoside compounds found in well-known ginseng adaptogens. We’d expect this extract to produce an additive or synergistic response when combined with other polyphenol ingredients, based on existing experimental evidence. The dose we’ve selected is within the hormetic range, a dose range we expect will produce positive adaptive responses over time.

Gynostemma pentaphyllum Key Mechanisms 

Mitochondrial Structure

  • Supports mitochondrial membrane integrity 1
  • Protects mitochondrial structure 2

Mitochondrial Function

  • Stimulates ATP Production/Output 1
  • Supports mitochondrial complex I-V performance 1
  • Supports citric acid cycle function — upregulates citrate synthase 1
  • Supports mitochondrial β-oxidation 3
  • Protects mitochondrial function 2

Signaling pathways

  • Upregulates AMP-activated protein kinase (AMPK) siganling 3,4
  • Downregulates mTOR signaling 5
  • Upregulates peroxisome proliferator-activated receptor alpha (PPARα) 6–9

Exercise performance (ergogenic effect)

  • Supports endurance performance 10
  • Downregulates lactic acid production 10
  • Supports oxygen supply to tissues by hemoglobin 10
  • Supports glucose uptake in muscle cells (in vitro) 3

Metabolism

  • Supports healthy insulin sensitivity 11–16
  • Supports healthy blood glucose levels 11,17
  • Supports metabolic homeostasis (activates AMPK, an energy sensor and metabolic regulator) 3,4

Body weight 

  • Supports β-oxidation (fatty acid metabolism) 3
  • Downregulates adipogenesis - downregulates peroxisome proliferator-activated receptor gamma (PPARγ) 3
  • Supports healthy body weight 3,18
  • Downregulates fat accumulation and blood/liver lipid levels 3,8,17
  • Supports healthy abdominal/visceral fat levels 18
  • Upregulates brown adipose tissue production 16

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]) 1,8,19–21
  • Replenishes glutathione (GSH) levels 20–22

Cellular signaling

  • Downregulates proinflammatory signaling (inducible nitric oxide synthase [iNOS], nuclear factor kappa B [NF-κB]) 6,23

Brain function

  • Protects cognitive function 19,24
  • Supports resistance to stress and mood — adaptogenic effect 25
  • Protects neurons from oxidative damage 19–22
  • Protects neurons from hypoxia 2
  • Protects neurons from neurotoxic agents 20–22,26
  • Upregulates brain-derived neurotrophic factor (BDNF) expression 24

Protection of organs and systems

  • Protects from cardiac injury and dysfunction 1,27
  • Protects from vascular injury and dysfunction 7,28
  • Protects liver structure and function 8,29,30
  • Protects kidney structure and function 31,32
  • Protects gastrointestinal structure and function 32,33

Gut microbiota

  • Regulates the composition of the gut microbiota 16,34,35
  • Regulates gut microbial metabolism
  • Modulates gut microbial gene expression
  • Supports healthy gut barrier function 34
  • Downregulates gut oxidative stress 
  • Downregulates gut inflammatory signaling 34

SYNERGIES

  • Grape seed extract (insulin sensitivity) 15

REFERENCES

1. Yu H, et al. Cell Stress Chaperones. 2016;21(3):429-437. doi:10.1007/s12192-016-0669-5
2. Schild L, et al. Phytomedicine. 2009;16(8):734-743. doi:10.1016/j.phymed.2009.03.006
3. Gauhar R, et al. Biotechnol Lett. 2012;34(9):1607-1616. doi:10.1007/s10529-012-0944-1
4. Nguyen PH, et al. Bioorg Med Chem. 2011;19(21):6254-6260. doi:10.1016/j.bmc.2011.09.013
5. Tai WC-S, et al. Proteomics. 2016;16(10):1557-1569. doi:10.1002/pmic.201500293
6. Huang TH-W, et al. J Biomed Sci. 2006;13(4):535-548. doi:10.1007/s11373-006-9076-8
7. Huang TH-W, et al. Eur J Pharmacol. 2007;565(1-3):158-165. doi:10.1016/j.ejphar.2007.03.013
8. Qin R, et al. Arch Pharm Res. 2012;35(7):1241-1250. doi:10.1007/s12272-012-0715-5
9. Huang TH-W, et al. Toxicol Appl Pharmacol. 2007;218(1):30-36. doi:10.1016/j.taap.2006.10.013
10. Lin-Na S, Yong-Xiu S. Afr J Tradit Complement Altern Med. 2014;11(3):112-117. PMID: 25371572.
11. Yeo J, et al. J Med Food. 2008;11(4):709-716. doi:10.1089/jmf.2007.0148
12. Huyen VTT, et al. J Nutr Metab. 2013;2013:765383. doi:10.1155/2013/765383
13. Huyen VTT, et al. Evid Based Complement Alternat Med. 2012;2012:452313. doi:10.1155/2012/452313
14. Huyen VTT, et al. Horm Metab Res. 2010;42(5):353-357. doi:10.1055/s-0030-1248298
15. Zhang H-J, et al. J Food Sci. 2009;74(1):H1-H7. doi:10.1111/j.1750-3841.2008.00976.x
16. Liu J, et al. J Agric Food Chem. 2017;65(42):9237-9246. doi:10.1021/acs.jafc.7b03382
17. Megalli S, et al. J Pharm Pharm Sci. 2006;9(3):281-291.
18. Park S-H, et al. Obesity . 2014;22(1):63-71. doi:10.1002/oby.20539
19. Zhang G-L, et al. Behav Pharmacol. 2011;22(7):633-644. doi:10.1097/FBP.0b013e32834afef9
20. Wang P, et al. J Int Med Res. 2010;38(3):1084-1092. doi:10.1177/147323001003800336
21. Wang P, et al. Brain Res Bull. 2010;83(5):266-271. doi:10.1016/j.brainresbull.2010.06.014
22. Shang L, et al. Brain Res. 2006;1102(1):163-174. doi:10.1016/j.brainres.2006.05.035
23. Aktan F, et al. Nitric Oxide. 2003;8(4):235-242. doi:10.1016/S1089-8603(03)00032-6
24. Hong S-W, et al. J Ethnopharmacol. 2011;134(3):1010-1013. doi:10.1016/j.jep.2011.02.002
25. Zhao TT, et al. BMC Complement Altern Med. 2015;15:323. doi:10.1186/s12906-015-0856-4
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35. Chen L, et al. PLoS One. 2015;10(5):e0126807. doi:10.1371/journal.pone.0126807

American Ginseng (Cereboost™)

PANAX QUINQUEFOLIUS COMMON NAME

American Ginseng

TOP BENEFITS OF PANAX QUINQUEFOLIUS

  • Enhances working memory and alertness*
  • Promotes calmness*
  • Supports cognitive function and performance*

WHAT IS PANAX QUINQUEFOLIUS?

Panax quinquefolius is commonly called American ginseng, because it is native to forested regions in North America. It is the same genus as Asian ginseng (Panax ginseng) and prized for many of the same reasons. Both American and Asian ginseng contain similar active constituents called ginsenosides. The ginsenosides are thought to be responsible for many of the adaptogenic (i.e., stress and fatigue support)  and health-promoting properties associated with ginseng.[1] While there are many different ginsenosides, the most well characterized include Rb1, Rb2, Rg1, Rc, Rd, and Re. Cereboost™ is a clinically studied and standardized American ginseng root extract. In humans studies, Cereboost™ has enhanced working memory and alertness, while promoting calmness.

NEUROHACKER’S PANAX QUINQUEFOLIUS SOURCING

Cereboost™ has been used in human clinical studies, where it has enhanced alertness, working memory, and calmness.

Cereboost™ was granted the NutrAward 2010 for the Best New Ingredient of the year.

Cereboost™ is produced by Naturex, an innovator in nutraceutical products in Europe and the United States.

Cereboost™ is standardized for total ginsenoside content (10-12%), and several specific ginsenosides, including Rb1 (4-7%), Rb2 (0.2-1.5%), Rg1 (0.1-0.4%), Rc (0.5-3.5%), Rd (0.9-3.0%), and Re (0.4-3.5%). 

Cereboost™ is non-GMO, gluten-free, and vegan.

Cereboost™is a trademark of Naturex.

PANAX QUINQUEFOLIUS DOSING PRINCIPLES AND RATIONALE

We consider Panax quinquefolius to be in the adaptogenic herb category; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is consistent with the studied amount in the human clinical studies for supporting working memory, alertness, and calmness.*

PANAX QUINQUEFOLIUS KEY MECHANISMS

Cognitive function

  • Supports attention [2]
  • Supports working memory [2,3]
  • Supports learning and memory [4–7]

Mood

  • Promotes calmness [2]
  • Supports mood [1,8,9]
  • Adaptogenic actions (i.e., stress resilience and anti-fatigue) [5]
  • Downregulates stress hormone levels / HPA-axis activation [1,8]

Brain function

  • Modulates cholinergic neurotransmission [1,4,5,10,11]
  • Downregulates acetylcholinesterase (AChE) activity [4]
  • Upregulates choline acetyltransferase (ChAT) expression [4]
  • Upregulates acetylcholine levels [4]
  • Modulates dopaminergic neurotransmission [12–15]
  • Modulates GABAergic neurotransmission [1,8]
  • Neuroprotective effects [1,4,5,8,10]
  • Regulates neural cytokine signaling [1,8,10,16]
  • Protects against glutamate neurotoxicity [10,17]
  • Supports neurite outgrowth, dendritic spine density, and synaptic plasticity [1,5–7]
  • Upregulates BDNF signaling [1,7,10,18]
  • Supports neurogenesis [1,10,18]

Antioxidant defenses

  • Upregulates antioxidant enzymes in the brain (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [8]
  • Replenishes glutathione (GSH) levels [8]
  • Downregulates lipid peroxidation [8]

Cardiometabolic effects

  • Supports healthy cardiometabolic parameters [19–21]
  • Supports healthy blood glucose levels [22–24]
  • Supports healthy insulin sensitivity [25]
  • Supports fat metabolism [19]
  • Supports mitochondrial enzyme complex activities [8]

 Gut microbiota

  • Regulates gut cytokine signaling [26–28]
  • Modulates gut microbiota composition [27,28]

Ergogenic effects

  • Supports high-intensity endurance performance [29,30]
  • Protects from exercise-induced muscle damage [29–31]


REFERENCES 

[1]H.J. Kim, P. Kim, C.Y. Shin, J. Ginseng Res. 37 (2013) 8–29.
[2]A. Scholey, A. Ossoukhova, L. Owen, A. Ibarra, A. Pipingas, K. He, M. Roller, C. Stough, Psychopharmacology 212 (2010) 345–356.
[3]A. Ossoukhova, L. Owen, K. Savage, M. Meyer, A. Ibarra, M. Roller, A. Pipingas, K. Wesnes, A. Scholey, Hum. Psychopharmacol. 30 (2015) 108–122.
[4]K. Shin, H. Guo, Y. Cha, Y.-H. Ban, D.W. Seo, Y. Choi, T.-S. Kim, S.-P. Lee, J.-C. Kim, E.-K. Choi, J.-M. Yon, Y.-B. Kim, Regul. Toxicol. Pharmacol. 78 (2016) 53–58.
[5]Y. Cheng, L.-H. Shen, J.-T. Zhang, Acta Pharmacol. Sin. 26 (2005) 143–149.
[6]I. Mook-Jung, H.S. Hong, J.H. Boo, K.H. Lee, S.H. Yun, M.Y. Cheong, I. Joo, K. Huh, M.W. Jung, J. Neurosci. Res. 63 (2001) 509–515.
[7]H. Zhao, Q. Li, X. Pei, Z. Zhang, R. Yang, J. Wang, Y. Li, Behav. Brain Res. 201 (2009) 311–317.
[8]P. Chanana, A. Kumar, Front. Neurosci. 10 (2016) 84.
[9]M. Chatterjee, P. Verma, G. Palit, Indian J. Exp. Biol. 48 (2010) 306–313.
[10]K. Radad, R. Moldzio, W.-D. Rausch, CNS Neurosci. Ther. 17 (2011) 761–768.
[11]C.G. Benishin, Neurochem. Int. 21 (1992) 1–5.
[12]G.-L. Wang, Y.-P. Wang, J.-Y. Zheng, L.-X. Zhang, Brain Res. 1699 (2018) 44–53.
[13]S.H. Lee, J. Hur, E.H. Lee, S.Y. Kim, Biomol. Ther. 20 (2012) 482–486.
[14]H.S. Kim, Y.T. Hong, K.W. Oh, Y.H. Seong, H.M. Rheu, D.H. Cho, S. Oh, W.K. Park, C.G. Jang, Gen. Pharmacol. 30 (1998) 783–789.
[15]H.S. Kim, K.S. Kim, K.W. Oh, Pharmacol. Biochem. Behav. 63 (1999) 407–412.
[16]C.F. Wu, X.L. Bi, J.Y. Yang, J.Y. Zhan, Y.X. Dong, J.H. Wang, J.M. Wang, R. Zhang, X. Li, Int. Immunopharmacol. 7 (2007) 313–320.
[17]Y.C. Kim, S.R. Kim, G.J. Markelonis, T.H. Oh, J. Neurosci. Res. 53 (1998) 426–432.
[18]L.-H. Shen, J.-T. Zhang, Neurol. Res. 26 (2004) 422–428.
[19]R.K. Singh, E. Lui, D. Wright, A. Taylor, M. Bakovic, Can. J. Physiol. Pharmacol. 95 (2017) 1046–1057.
[20]V. Vuksan, Z.Z. Xu, E. Jovanovski, A.L. Jenkins, U. Beljan-Zdravkovic, J.L. Sievenpiper, P. Mark Stavro, A. Zurbau, L. Duvnjak, M.Z.C. Li, Eur. J. Nutr. (2018).
[21]I. Mucalo, E. Jovanovski, D. Rahelić, V. Božikov, Z. Romić, V. Vuksan, J. Ethnopharmacol. 150 (2013) 148–153.
[22]V. Vuksan, M.P. Stavro, J.L. Sievenpiper, V.Y. Koo, E. Wong, U. Beljan-Zdravkovic, T. Francis, A.L. Jenkins, L.A. Leiter, R.G. Josse, Z. Xu, J. Am. Coll. Nutr. 19 (2000) 738–744.
[23]V. Vuksan, J.L. Sievenpiper, V.Y. Koo, T. Francis, U. Beljan-Zdravkovic, Z. Xu, E. Vidgen, Arch. Intern. Med. 160 (2000) 1009–1013.
[24]V. Vuksan, J.L. Sievenpiper, J. Wong, Z. Xu, U. Beljan-Zdravkovic, J.T. Arnason, V. Assinewe, M.P. Stavro, A.L. Jenkins, L.A. Leiter, T. Francis, Am. J. Clin. Nutr. 73 (2001) 753–758.
[25]L.R. De Souza, A.L. Jenkins, E. Jovanovski, D. Rahelić, V. Vuksan, J. Ethnopharmacol. 159 (2015) 55–61.
[26]C.-Z. Wang, H. Yao, C.-F. Zhang, L. Chen, J.-Y. Wan, W.-H. Huang, J. Zeng, Q.-H. Zhang, Z. Liu, J. Yuan, Y. Bi, C. Sava-Segal, W. Du, M. Xu, C.-S. Yuan, Int. Immunopharmacol. 64 (2018) 246–251.
[27]C.-Z. Wang, C. Yu, X.-D. Wen, L. Chen, C.-F. Zhang, T. Calway, Y. Qiu, Y. Wang, Z. Zhang, S. Anderson, Y. Wang, W. Jia, C.-S. Yuan, Cancer Prev. Res. 9 (2016) 803–811.
[28]C.-Z. Wang, W.-H. Huang, C.-F. Zhang, J.-Y. Wan, Y. Wang, C. Yu, S. Williams, T.-C. He, W. Du, M.W. Musch, E.B. Chang, C.-S. Yuan, Clin. Transl. Oncol. 20 (2018) 302–312.
[29]J. Wu, S. Saovieng, I.-S. Cheng, T. Liu, S. Hong, C.-Y. Lin, I.-C. Su, C.-Y. Huang, C.-H. Kuo, J. Ginseng Res. (2018).
[30]C.-W. Hou, S.-D. Lee, C.-L. Kao, I.-S. Cheng, Y.-N. Lin, S.-J. Chuang, C.-Y. Chen, J.L. Ivy, C.-Y. Huang, C.-H. Kuo, PLoS One 10 (2015) e0116387.
[31]M. Estaki, E.G. Noble, Appl. Physiol. Nutr. Metab. 40 (2015) 116–121.

KSM-66 Ashwagandha®​ (​Withania somnifera​) Root Extract

KSM-66 ASHWAGANDHA® COMMON NAME

Ashwagandha | Indian ginseng

TOP BENEFITS OF KSM-66 ASHWAGANDHA®

Supports sleep*
Supports stress relief*
Supports memory and cognition*
Supports muscle strength and endurance*
Supports sexual health*
Supports a healthy body weight*
Supports thyroid health*

WHAT IS KSM-66 ASHWAGANDHA®

KSM-66 Ashwagandha is a full-spectrum ashwagandha root extract. Ashwagandha (i.e., Indian ginseng) is a Rasayana—the category of elixirs and tonic herbs prized by the branch of Ayurvedic medicine concerned with rejuvenation and focused on promoting a youthful state of physical and mental health. Ashwagandha holds a prominent place among the Rasayana herbs, where it was used for many reasons including as general tonic and to infuse energy and vigor in circumstances characterized by exhaustion or a lack of physical energy. A key attribute is that ashwagandha promotes balance. As the English name Indian ginseng implies, ashwagandha was believed to share some of the attributes of ginseng, in essence supporting multiple areas of health and well-being, especially under conditions characterized by increased stress. Herbs that produce these types of nonspecific resistance to and recovery from stress—and which typically also support general well-being, healthy energy, and homeostasis—are called adaptogens. Among its studied benefits, KSM-66 Ashwagandha® supports sleep quality, relaxation, muscle recovery, cognitive function, immunity and a healthier stress response.

NEUROHACKER’S KSM-66 ASHWAGANDHA® SOURCING

KSM-66 Ashwagandha® was the product of 14 years of R&D. It is the most researched brand of ashwagandha, with a research focus on what happens in healthy people when they take the ingredient.

Created by Ixoreal Biomed Inc., the world's ashwagandha experts. Ixoreal owns the entire production chain from farm to the finished ingredient, allowing them to deliver high-quality ashwagandha with batch-to-batch consistency.

KSM-66 Ashwagandha® is a “full-spectrum” root extract, which means it is designed to maintain the balance of the various constituents found in the root. It is standardized for≥5% with anolides and <0.1% with aferin A.

KSM-66 Ashwagandha® has won awards as an innovative ingredient and for sports nutrition. It has also qualified for an extensive number of certifications including Organic, Non-GMO, GRAS, Vegan and Gluten-Free.

KSM-66 Ashwagandha® is a registered trademark of Ixoreal Biomed Inc.

KSM-66 ASHWAGANDHA® DOSING PRINCIPLES AND RATIONALE

We consider ashwagandha to be an herbal adaptogen, so expect it to follow hormetic dosing principles. Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. Based on studies where different doses have been given in the same study, we also consider ashwagandha dosing to be somewhat akin to the Pareto Principle (i.e., 80-20 rule), because much of the benefits have occurred at a lower dose, and relatively modest additional gains are achieved at doses two- to four-fold higher (see Neurohacker Dosing Principles). Because of both of these reasons, it’s important to identify the lowest dose that can produce many of the desired responses when using ashwagandha. Since we also use ashwagandha in more than one product, it’s also important to us to ensure that a user taking several of our products will not inadvertently take too much ashwagandha. The most common dose of KSM-66 Ashwagandha® in human studies has been 300mg taken twice a day (i.e., 600mg a day total). We consider this to be the upper end of the total amount of daily ashwagandha that we’d want a customer to take over a long period of time, and 300mg to be the maximum at a given time of day (i.e., if being taken at dinner as an example). We consider the lower end of the beneficial range to be about 125-150mg depending on the ashwagandha extract being used.

KSM-66 ASHWAGANDHA® KEY MECHANISMS

Sleep

Supports sleep onset[1,2]

Supports sleep efficiency[1]

Supports quality of sleep[1,3]

Supports slow-wave sleep[2]

Supports total sleep time[2]

Mood and stress

Supports a calm mood[1,4]

Supports stress management[5–7]

Supports health cortisol levels[5–7]

Brain function

Supports cognitive and psychomotor performance[8,9]

Supports memory, executive function, attention, and information processing speed[10]

Supports GABAergic neurotransmission[2,11]

Supports GABA receptor signaling[12–14]

Supports dopamine levels[15]

Downregulates the basal activity levels of acetylcholine esterase[15]

Supports neuroprotection – protects from neuronal mitochondrial swelling and apoptosis; protects cognitive function (ischemia, oxidative stress)[16]
Protects from neurotoxicity[15,17]

Immune system

Supports innate immunity[18–22]

Supports adaptive immunity[18,19,22–31]

Supports immune system communication[22,32–34]

Mitochondrial function

Supports mitochondrial membrane potential and structural integrity[16]

Protects from mitochondrial damage[16]

Protects from mitochondrial membrane permeabilization[35]

Protects from complex I-V Inhibition (protects electron transport chain and oxidative phosphorylation performance)[15–17,36]

Supports citric acid cycle enzymes[36]

Exercise and sports

Supports endurance performance[37,38]

Supports muscle strength[39,40]

Supports post-exercise recovery[40]

Metabolic function

Supports healthy insulin sensitivity[4,41–44]

Supports healthy blood glucose levels[41–45]

Supports healthy leptin signaling[4,44]

Supports healthy body weight[4,44]

Supports healthy feeding behaviors[4,5]

Supports lean mass[40]

Antioxidant defenses

Supports antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT],glutathione peroxidase [GPx])[15–17,45,46]

Replenishes glutathione (GSH) levels[15,16,45]

Counters oxidative stress and reactive oxygen species levels[15,16,35,47]

Cellular signaling

Downregulates the expression of some cytokines including tumor necrosis factor alpha(TNFα), interleukin 1 beta (IL-1β), and IL-6[4,41,42]

Thyroid function

Supports thyroid function[48–50]

Healthy aging and longevity

Lifespan extension effects (Caenorhabditis elegans)[47,51]

Upregulates insulin-like growth factor-1 (IGF-1) signaling pathway[47,51]

Downregulates α-synuclein and amyloid-β aggregation[47]

Upregulates FOXO3A and SIRT3[52]

References

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Hawthorn Leaf and Flower Extract

HAWTHORN COMMON NAME

Hawthorn | Quickthorn | Thornapple | May-tree | Whitethorn | Hawberry

TOP BENEFITS OF HAWTHORN

Supports cardiovascular health*
Supports mental well-being*
Supports a calm mood*

WHAT IS HAWTHORN?

The leaf and flowers of Hawthorn— Crataegus sp. such as C. monogyna and C. oxyacantha —was a heart tonic (i.e., something intended to make the heart function more efficiently) and used as support for an aging heart in European herbal traditions. Other traditional uses include when extra support was desired for stress, nervousness, mental well-being and sleep. Interesting aspects of hawthorn lore are comments in herbal texts related to removing a hurried feeling, having a calming effect on the nerves and the heart, and being a mood brightener. In other words, hawthorn was used to support the heart both physically and emotionally. In Celtic Lore, hawthorn was believed to have the power to put people to sleep, though this has not been something that’s ever been studied in humans. Hawthorn research has focused primarily on the cardiovascular system and supports hawthorn having restorative benefits when taken over time. While not nearly as researched for relaxation, mood and sleep, available research, mostly done in animals, or combined with one or more other ingredients, have been supportive of these traditional uses. Hawthorn’s main bioactive components are flavonoids, particularly oligomeric proanthocyanidins, vitexin-2 rhamnoside and hyperoside.

NEUROHACKER’S HAWTHORN SOURCING

Hawthorn leaf and flower extract is a standardized extract, containing a minimum of 1.8% vitexin-2 rhamnoside and hyperoside, and a minimum of 1.2% flavonoids, calculated as hyperoside. Supplied by EUROMED S.A., a leading producer of premium standardized herbal extracts. EUROMED extracts are in compliance with worldwide GMP (Good Manufacturing Practices) norms, international pharmacopoeias and international regulations.

Hawthorn leaf and flower extract is Non-GMO and Vegan.

HAWTHORN DOSING PRINCIPLES AND RATIONALE

Hawthorn extracts are generally thought to be dose-dependent, with 160 to 900 mg of a standardized extract being the commonly used dose range. For many ingredients that are dose-dependent, response does not go up in a straight line. Instead, responses tend to be more S-shaped, with much of the benefits occurring within a narrow range, typically towards the lower-to-middle of the overall dosing range (see Neurohacker Dosing Principles). In general, when used in generally healthy adults, especially for reasons related to hawthorn’s traditional uses for stress, nervousness, mental well-being and sleep, our preference is to use doses at or close to the lower end of the range. If used for specific heart health reasons, higher doses may be preferred.

HAWTHORN KEY MECHANISMS

Brain function
Supports cognitive functions[1–3]
Supports neuroprotective functions[1,4,5]
Supports brain antioxidant defenses[1,5]
Down-regulates acetylcholinesterase (AChE)[1,6]

Mood and well-being
Supports a calm mood[7–10]

Cardiovascular health
Supports healthy cardiovascular function[7,11,12]
Supports cardiovascular stem/progenitor cells[13]

Immune system
Supports adaptive immunity[14,15]


REFERENCES

[1] M. Saoudi, R.B. Slama-Ben Salem, M.B. Salem, N. Brahmi, R. Badraoui, M. Nasri, A. El Feki, Biomed. Pharmacother. 114 (2019) 108795.
[2] A. Pirmoghani, I. Salehi, S. Moradkhani, S.A. Karimi, S. Salehi, IBRO Rep 7 (2019) 90–96.
[3] E. Zarrinkalam, K. Ranjbar, I. Salehi, N. Kheiripour, A. Komaki, Biomed. Pharmacother. 97 (2018) 503–510.
[4] D.-L. Zhang, Y.-T. Zhang, J.-J. Yin, B.-L. Zhao, J. Neurochem. 90 (2004) 211–219.
[5] C. Elango, K.S. Jayachandaran, S. Niranjali Devaraj, Int. J. Dev. Neurosci. 27 (2009) 799–803.
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[7] A.F. Walker, G. Marakis, A.P. Morris, P.A. Robinson, Phytotherapy Research 16 (2002) 48–54.
[8] M. Hanus, J. Lafon, M. Mathieu, Curr. Med. Res. Opin. 20 (2004) 63–71.
[9] M. Bourin, T. Bougerol, B. Guitton, E. Broutin, Fundam. Clin. Pharmacol. 11 (1997) 127–132.
[10] O.D. Can, U.D. Ozkay, N. Oztürk, Y. Oztürk, Pharm. Biol. 48 (2010) 924–931.
[11] N. Idris-Khodja, C. Auger, E. Koch, V.B. Schini-Kerth, Phytomedicine 19 (2012) 699–706.
[12] A.I.A. Al-Gareeb, Mustansiriya Medical Journal 11 (2012) 52–57.
[13] J. Halver, K. Wenzel, J. Sendker, C. Carrillo García, C.A.J. Erdelmeier, E. Willems, M. Mercola, N. Symma, S. Könemann, E. Koch, A. Hensel, D. Schade, Front. Pharmacol. 10 (2019) 1357.
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[15] X. Tan, Z. Sun, Z. Huang, C. Zhou, H. Lin, L. Tan, P. Xun, Q. Huang, Fish Shellfish Immunol. 70 (2017) 656–664.

Holy Basil (Ocimum sanctum) Leaf Extract

HOLY BASIL COMMON NAME

Holy Basil | Sacred Basil | Tulsi | Tulasi

TOP BENEFITS OF HOLY BASIL

Supports a calm mood*
Supports cognitive function*
Support a healthy stress response*
Supports general immune health*

WHAT IS HOLY BASIL?

Holy Basil (Ocimum sanctum; synonym Ocimum tenuiflorum) is a culinary and medicinal aromatic herb that has been used within Ayurvedic medicine for more than 3000 years[1]. In Ayurvedic medicine holy basil is called “tulsi,” which translates as “the incomparable one.” It is one of a small number of herbs categorized as Rasayana, the category applied to elixirs and tonic herbs prized for rejuvenation and revitalization. It was believed to guard the body from stress of all types while keeping the mind sharp and the body healthy. In modern times, holy basil is categorized as an adaptogen, supporting a healthy stress response. Holy basil also supports mood, cognition and immunity. Holy basil’s bioactive molecules include ursolic acid, rosmarinic acid, eugenol, ocimumosides A and B, ocimarin, apigenin and lutein[2,3].

NEUROHACKER’S HOLY BASIL SOURCING

Holy Basil is a leaf extract standardized to contain not less than 2% ursolic acid.

Holy Basil is Non-GMO and Vegan.

HOLY BASIL DOSING PRINCIPLES AND RATIONALE

Because holy basil is an Ayurvedic Rasayana herb, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker Dosing Principles ). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. For herbs that are adaptogens, especially when they will be used for extended periods of time, we think it’s important to identify the lowest dose that can produce many of the desired responses. Different doses of holy basil have been used in human studies. Functional benefits have occurred at low doses (~300mg) and at doses four-fold higher (1200mg). Considered collectively, human studies suggest holy basil dosing may be somewhat akin to the Pareto Principle (i.e., 80-20 rule), where 80%+ of the benefits happen at 20% of the dose. Our goal with holy basil, as with all ingredient choices, is to select the appropriate dose keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogen extracts, we are likely to use less holy basil than if the only herbal adaptogen we were using was holy basil.

HOLY BASIL KEY MECHANISMS

Mood and stress response
Supports a calm mood[4–11]
Supports a positive mental-emotional bias[6,9]
Supports healthy stress hormone levels[4,7,8,12,13]

Brain function
Supports memory and learning[5,14,15]
Supports working memory[4]
Supports executive function[4]
Supports attention[6]
Supports sleep[5]
Supports serotonin signaling[16–18]
Supports dopamine signaling[16–18]
Supports adrenergic signaling[17,18]
Supports acetylcholine signaling[19,20]
Down-regulates acetylcholinesterase (AChE) activity[19,21]
Up-regulates choline acetyltransferase (ChAT) expression[14,22]
Supports brain antioxidant defenses[18,23–25]
Supports neuroprotective functions[15,18,23–27]

Immune System
Supports innate immunity[28]
Supports adaptive immunity[28–31]

General health
Supports gastroprotective functions[32,33]
Supports healthy metabolism[34,35]


REFERENCES

[1] N. Jamshidi, M.M. Cohen, Evid. Based. Complement. Alternat. Med. 2017 (2017) 9217567.
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[22] P. Hening, M.B. Mataram Auriva, N. Wijayanti, D.L. Kusindarta, H. Wihadmadyatami, Vet World 11 (2018) 1237–1243.
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Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

REISHI MUSHROOM COMMON NAME

Reishi | Lingzhi | Ganoderma

TOP BENEFITS OF REISHI MUSHROOM 

Supports general immune health*

Supports sleep*

WHAT IS REISHI MUSHROOM?

Ganoderma lucidum is considered the “mushroom of immortality” and called Reishi in Japanese—this is the name it’s most known as in America—and Lingzhi in Chinese. In Traditional Chinese Medicine, it is considered to be a shen tonic. Shen tonics were believed to play roles in supporting peace of mind, joy, emotional balance, optimism, sound sleep, and clear thinking. Reishi’s traditional uses, which included replenishing Qi, easing and centering the mind, increasing resistance to fatigue, promoting well-being, and supporting sleep, are consistent with this role as a shen tonic. It was thought to be ideal for countering restlessness and quieting an overactive mind. In addition to these traditional uses, modern research on reishi mushrooms has focused on immune system support and rejuvenating processes, including stem cell function.*

Reishi extracts contain a variety of compounds, most notably, polysaccharides (including beta glucans), peptidoglycans, and triterpenoid compounds (including lucidenic acids). Reishi also contains low amounts of nucleosides (adenosine, cytidine, guanosine, inosine, thymidine, uridine), nucleotide bases (adenine, guanine, hypoxanthine, thymine and uracil), and the neurotransmitter GABA [1–3]. 

NEUROHACKER’S REISHI MUSHROOM SOURCING

Reishi mushroom extract is from the fruiting body, not the mycelium. The fruiting body is what is usually thought of as the “actual” mushroom, as opposed to the mycelium, which is akin to the “root” system of a mushroom.

Reishi mushroom is concentrated through the extraction process (i.e., grams of mushroom are needed to produce one gram of the extract) resulting in a final extract with not less than 30% polysaccharides, since these compounds are linked to general immune support.

Reishi mushroom is Non-GMO and Vegan.

REISHI MUSHROOM DOSING PRINCIPLES AND RATIONALE

Because reishi is thought of as being an adaptogenic mushroom, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone, so our focus with reishi is to provide an amount within this range. When deciding on a dose for a mushroom like reishi, it’s also important to consider the concentration, because more concentrated extracts require lower mg amounts than crude extracts. And finally, it’s important to consider whether the extract is made from fruiting bodies only, or uses mycelium, since the fruiting bodies are the part of a mushroom that concentrates active compounds. Our goal with reishi, as with all ingredient choices, is to select the appropriate dose keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogen extracts, we are likely to use less reishi than if the only adaptogen we were using was reishi.

REISHI MUSHROOM KEY MECHANISMS

Brain function

Supports learning and memory [4,5]

Supports sleep [6–13]

Supports neurogenesis [5,14]

Upregulates neural progenitor cell (NPC) proliferation [5]

Supports brain mitochondrial function [4,15,16]

Supports nerve growth factor (NGF) [17]

Supports neuroprotective functions [14,17,18]

Supports brain antioxidant defenses [4,15,16]

Stress

Supports healthy behavioral and physiological responses to stress [19]

Gut Microbiota 

Supports the composition of the gut microbiota [20–27]

Supports microbial metabolism [21,26,28]

Supports gut immunity [21,27]

Supports intestinal barrier function [27]

Immune System

Supports general immune health [29–33]

Supports innate immunity [34–47]

Supports adaptive immunity [36–38,42,45,48–51]

Supports immune signaling [31,38,41]

Healthy aging and longevity

Supports mitochondrial function [15,18]

Supports mitochondrial biogenesis [17]

Supports autophagy [18,52]

Supports AMPK signaling [18,53]

Supports mTOR signaling [18,52–54]

Supports stem cell proliferation [55,56]

Supports stem cell differentiation [57]

Supports antioxidant defenses [58]

REFERENCES

[1]S. Wachtel-Galor, J. Yuen, J.A. Buswell, I.F.F. Benzie, in: I.F.F. Benzie, S. Wachtel-Galor (Eds.), Herbal Medicine: Biomolecular and Clinical Aspects, CRC Press/Taylor & Francis, Boca Raton (FL), 2012.

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[5]S. Huang, J. Mao, K. Ding, Y. Zhou, X. Zeng, W. Yang, P. Wang, C. Zhao, J. Yao, P. Xia, G. Pei, Stem Cell Reports 8 (2017) 84–94.

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[15]T.A. Ajith, N.P. Sudheesh, D. Roshny, G. Abishek, K.K. Janardhanan, Exp. Gerontol. 44 (2009) 219–223.

[16]N.P. Sudheesh, T.A. Ajith, V. Ramnath, K.K. Janardhanan, Clin. Nutr. 29 (2010) 406–412.

[17]L.-W. Chen, L.-Y. Horng, C.-L. Wu, H.-C. Sung, R.-T. Wu, Neuropharmacology 63 (2012) 719–732.

[18]Z.-L. Ren, C.-D. Wang, T. Wang, H. Ding, M. Zhou, N. Yang, Y.-Y. Liu, P. Chan, Acta Pharmacol. Sin. 40 (2019) 441–450.

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[24]W.-L. Guo, Y.-Y. Pan, L. Li, T.-T. Li, B. Liu, X.-C. Lv, Food Funct. 9 (2018) 3419–3431.

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Rosmarinus officinalis Leaf Extract

Rosemary Extract Common Name

Rosemary | Garden Rosemary

Top Benefits of Rosemary Extract

  • Supports healthy aging*
  • Supports exercise performance*
  • Supports muscle structure and function*
  • Supports healthy metabolic pathways*
  • Supports healthy weight*
  • Supports mitochondrial biogenesis, structure and function*
  • Supports antioxidant defenses*
  • Supports healthy cellular responses*
  • Supports brain function*
  • Supports cardiovascular function*
  • Supports liver function*
  • Supports healthy gut microbiota*  

What is Rosemary Extract?

Rosemary is a member of the mint family. It's common name derives from Latin and translates as “dew of the sea.” Rosemary was used as a spice and folk medicine by Egyptians, Greeks, and Latins cultures, thriving close to the coast especially in dryer areas throughout the Mediterranean. Rosmarinus officinalis contains a range of health-supporting polyphenols, including diterpenes (e.g., carnosol, carnosic acid, rosmarinic acid) and a triterpene called ursolic acid (sometimes referred to as urson, prunol, malol, or 3-beta-3-hydroxy-urs-12-ene-28-oic-acid). Triterpenes are produced by plants as part of their self-defense mechanism, so tend to concentrate in areas that come in direct contact with the external environment. This is the case with ursolic acid: It was originally identified in the epicuticular waxes of apple peels as early as 1920’s. While all apple peels contain some ursolic acid, the amount varies about 4-fold depending on variety. Fuji and Smith apple varieties are the best source, with the peel of medium-sized apple containing about 50 mg[1]. Ursolic acid is also found in the peels of other fruits, and in kitchen spice herbs like basil, rosemary and thyme. Ursolic acid supports a variety of functional areas, many of which overlap with the response to exercise (e.g., support antioxidant defenses, enhance insulin sensitivity, stimulate mitochondrial biogenesis, upregulat sirtuins, activate AMPK). One of it’s more unique functional support areas is as a resistance training mimetic, supporting the development of new muscle fibers and muscle rejuvenation.

Neurohacker’s Rosemary Extract Sourcing

Rosemary Extract was selected because it’s standardized to contain 50% ursolic acid.

We opted for a rosemary extract for two reasons. Ursolic acid from rosemary extract is what’s been used in human clinical studies. Second, rosemary is complementary to ursolic acid, supporting antioxidant defenses, cellular detoxification and protective functions.

Studies of this extract suggest it supports muscle growth, rejuvenation, and performance. *

Rosemary Extract Dosing Principles and Rationale

Many polyphenol compounds have produce either a threshold response or follow hormetic dosing principles (see Neurohacker Dosing Principles). Because one of the main active compounds in rosemary extract is polyphenol ursolic acid, we expect the extract to have a hormetic range (i.e., a dosing range above which results could be poorer). Extrapolating from animal and human experiments, we expect this range to be from about 100 to 450 mg. We have selected to dose towards the lower end of the range, because we anticipate it having additive or synergistic effects with other polyphenol ingredients.*

Rosemary Extract Key Mechanisms

 Mitochondrial biogenesis

  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α)[2]
  • Upregulates PGC-1β[3,4]
  • Upregulates cAMP-PKA-CREB signaling pathway[5]
  • Upregulates nuclear transcription factors of mitochondrial biogenesis (mitochondrial transcription factor A [TFAM])[2]

Mitochondrial structure and function

  • Upregulates mitochondrial mass[2]
  • Promotes ATP production[2]
  • Upregulates signaling pathways: AMP-activated protein kinase (AMPK)[2,6–9]
  • Supports complex IV (cytochrome C oxidase) performance[2]
  • Supports mitochondrial β-oxidation – upregulates peroxisome proliferator-activated receptor alpha (PPARα)[10]

Exercise performance (ergogenic effects)

  • Supports endurance performance[2,11,12]
  • Supports muscle strength[2,11–13]

Muscle Structure/Function

  • Upregulates muscle mass and the size of skeletal muscle fibers[8,11,12]
  • Promotes the generation of new muscle fibers[14,15]
  • Supports post-exercise recovery and skeletal muscle damage prevention[16]
  • Upregulates muscle cell glucose uptake via AMPK activation[7–9]
  • Upregulates insulin-like growth factor-1 (IGF-1) signaling in skeletal muscle[8,11]
  • Downregulates lactic acid production[12]

Metabolism

  • Supports healthy insulin sensitivity[10,17–23]
  • Upregulates glucose regulatory enzymes[24]
  • Supports citric acid cycle function via upregulation of citrate synthase[2]
  • Upregulates insulin-like growth factor-1 (IGF-1) in the blood[13]

Body weight 

  • Supports healthy body weight[6,11,18]
  • Promotes lean mass[11,12]
  • Promotes energy expenditure[6]
  • Downregulates fat accumulation and blood/liver lipid levels [6,8,10,11,13,17,19]
  • Promotes free fatty acid uptake and β-oxidation and prevents intracellular fat storage in skeletal muscle cells[6]
  • Upregulates adiponectin concentrations[10]
  • Promotes brown adipose tissue production[11]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx])[25–30]
  • Downregulates reactive oxygen species (ROS) production[2,26]
  • Replenishes glutathione (GSH) levels[17,26]

Cellular signaling 

  • Upregulates peroxisome proliferator-activated receptor alpha (PPARα) in the spinal cord; regulates peripheral cytokine signaling[31]
  • Downregulates tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels[17,28]

Brain function

  • Upregulates longevity biomarkers in the hypothalamus[4]
  • Downregulattes ROS and oxidative stress in the brain[26]
  • Supports spatial learning and memory (in rats)[25,29]
  • Protects from neuronal degeneration[29]
  • Downregulates oxidative stress in the hippocampus[29]
  • Regulates cytokine signaling in the hippocampus[29]

Cardiovascular function

  • Supports healthy cholesterol levels[10,28]
  • Supports vascular health[32,33]

Liver function

  • Promotes hepatic autophagy[10]
  • Upregulates xenobiotic detoxification enzymes: NAD(P)H-quinone reductase and glutathione-S-transferase[34,35]
  • Mediates hepatic protection[3]

Gut microbiota

  • Regulates the composition of the gut microbiota[36]
  • Regulates gut microbial metabolism[36]

Healthy aging and longevity

  • Upregulates SIRT1 and SIRT6[3,4,33,37,38]
  • Supports "mild" mitochondrial uncoupling: upregulates mitochondrial uncoupling protein 1 (UCP1) and UCP3[2,6,11]
  • Upregulates the expression of Klotho[3,4]
  • Downregulates advanced glycation end-products (AGEs)[17,39,40]
  • Inhibits poly [ADP-ribose] polymerase 1 (PARP1, also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1)[41]


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Schisandra chinensis Fruit Extract

SCHISANDRA CHINENSIS COMMON NAME

Schisandra | Schizandra | Magnolia Berry | Five-Flavor-Fruit | Limonnik (Russian)

TOP BENEFITS OF SCHISANDRA CHINENSIS

Supports cognitive function*
Supports mood*
Supports resistance to stress*
Supports endurance capacity*
Supports sleep*

WHAT IS SCHISANDRA CHINENSIS?

The fruits of Schisandra chinensis are berries. They are one of the 50 fundamental herbs in Traditional Chinese Medicine, and have been used in traditional medicine in Japan, Korea, and Far East regions of the Russian empire. One of its common names—Five-Flavor-Fruit—is because the berries are known for possessing all five basic flavors: salty, sweet, sour, pungent (spicy), and bitter. S. chinensis fruits are considered to be an adaptogen, supporting broad resistance to stress, mental and physical performance, mood, sleep, vision, and immunity. Several of its traditional uses, including use as a tonic to counter exhaustion and support night vision, led to Russian scientists extensively studying the berries and seeds in both animals and humans from 1940-1960. As a result of this research S. chinensis gained recognition as an adaptogen in the early 1960’s in the former USSR, and has continued to be extensively studied in articles published in Russian, and more recently in English language journals. The primary active compounds in S. chinensis berries are schisandra lignans—lignans are a subgroup of non-flavonoid polyphenols that interact with gut microbiota (i.e., gut-brain axis) [1].

NEUROHACKER’S SCHISANDRA CHINENSIS SOURCING

Schisandra chinensis fruit extract is standardized to contain not less than 9% schisandrins.

Schisandra chinensis fruit extract is Non-GMO and Vegan.

SCHISANDRA CHINENSIS DOSING PRINCIPLES AND RATIONALE

The original Russian research resulted in Schisandra chinensis being categorized as an herbal adaptogen. Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response (see Neurohacker Dosing Principles). It’s important to be in this zone; it’s just as important not to be above it. The Russian research also found that the amount of the schisandra lignans given were critical when determining the dose, with very low doses of these compounds being nootropic and ergogenic. So, when an extract is standardized for higher amounts of schisandrins, lower amounts of it should be taken. Our dosing of S. chinensis is determined based on the standardization in order to provide an amount of schisandra lignans in the target range for a healthy adaptive response.

SCHISANDRA CHINENSIS KEY MECHANISMS

Adaptogen

Supports endurance and working capacity [1]

Supports resistance to stress [1–8]

Supports sleep [1]

Supports a calm mood [1,9]

Supports healthy behavioral responses to stress [3,4,7]

Brain function

Supports mental performance [1]

Supports vision [1]

Supports learning and memory [7,10–13]

Supports GABAergic neurotransmission [3,14,15]

Supports GABA-Glutamate levels [10,11,15,16]

Supports acetylcholine signaling [10,11,13]

Supports serotonin signaling [9–11,16]

Supports adrenergic signaling [9–11,16]

Supports dopamine signaling [9–11,16]

Supports sleep mechanisms [14,15,17,18] 

Downregulates acetylcholinesterase (AChE) activity [10,13]

Supports brain-derived neurotrophic factor (BDNF) [4,7]

Modulates glycogen synthase kinase 3β (GSK3β) activity [7,10] 

Supports neuroprotective functions [10–13,19,20]

Supports brain mitochondrial function [21]

Supports antioxidant defenses [10,19,21,22]

Supports phase II detoxifying/antioxidant enzymes [22]

Gut microbiota

Supports the composition of the gut microbiota [23,24]

Supports gut microbial metabolism [24]

Supports gut immune responses [24]

Immune System

Supports innate immunity [25–27]

Supports immune function during some forms of stress [2,28–30]

Supports immunomodulation (i.e., balance of immune function) [31–33]

Healthy aging and longevity

Supports mitochondrial function [19,21,34]

Supports antioxidant defenses [21,34]

Supports HSP70 chaperone [34]

Supports autophagy [35]

Supports healthy muscle and bone with aging [36,37]

Synergies

With sesamin (from sesame seeds)—another lignan—to support liver health [38] and blood fluidity [39]

With other adaptogens (e.g., Rhodiola, Siberian Ginseng) as a nootropic and immune support [40,41]


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Sirtmax® Kaempferia parviflora

Kaempferia parviflora Common Name

Black Ginger | Black Turmeric | Krachai Dam

Top Benefits of Kaempferia parviflora

  • Supports mitochondrial biogenesis, structure and function*
  • Supports muscle strength and endurance*
  • Supports metabolism & healthy blood sugar levels*
  • Supports healthy weight*
  • Supports antioxidant defenses*
  • Supports healthy aging*
  • Support cardiovascular function*
  • Supports brain function*
  • Supports reproductive health*

What is Kaempferia parviflora?

Kaempferia parviflora is found in the upper Northeastern regions of Thailand. Root extracts have a long history of use and a reputation for being a health tonic and energy enhancer (i.e., Thai ginseng). The novel active constituents are a special type of polyphenol called polymethoxyflavonoids. Sirtmax® Kaempferia parviflora root extract is standardized for polymethoxyflavonoid content.

Neurohacker’s Kaempferia parviflora Sourcing

Sirtmax® has been used in animal and human research studies.

Created by Tokiwa Phytochemicals, a leader in standardized Kaempferia parviflora supplementation. 

Highest concentration, full-spectrum root extract, with double standardization for 5,7-dimethoxyflavone (≥ 4%) along with five Kaempferia parviflora polymethoxyflavonoids (≥ 15%).

Grown in Thailand & Laos.

Sirtmax® is a registered trademark of Tokiwa Phytochemical Co., Ltd.

Kaempferia parviflora Dosing Principles and Rationale

We consider Kaempferia parviflora to be in the adaptogenic herb category; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is within the studied range in humans.*

Kaempferia parviflora Key Mechanisms

Mitochondrial biogenesis

  • Upregulates mitochondrial number[1]
  • Upregulates Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1alpha (PGC-1α)[1–3]
  • Upregulates transcription factors for mitochondrial biogenesis (estrogen-related receptor-α [ERRα], nuclear respiratory factor-1 [Nrf-1], and mitochondrial transcription factor A [TFAM]) through activation of PGC-1α[2]

Mitochondrial function

  • Upregulates AMP-Activated Protein Kinase (AMPK)[2,3]
  • Promotes ATP production (output of mitochondrial oxidative phosphorylation)[3]
  • Promotes mitochondrial β-oxidation (fatty acid metabolism) – upregulates peroxisome proliferator-activated receptor gamma (PPARγ) and delta (PPARδ)[2,4]

Exercise performance (ergogenic effects)

  • Supports endurance performance[1,2,5,6]
  • Supports post-exercise recovery[1]
  • Supports muscle strength[5,6]
  • Supports muscle metabolism (upregulates glycogen synthase and increases glycogen content)[1]

Metabolism

  • Supports healthy insulin sensitivity[7]
  • Promotes cell metabolism (muscle cell precursors [myoblasts] in vitro): promotes glucose uptake and the downregulation of lactic acid production; promotes the expression of glucose transporter 4 (GLUT4) and monocarboxylate transporter 1 (MCT1)[3]

Body weight

  • Downregulates fat accumulation and blood/liver lipid levels[4,7,8]
  • Promotes differentiation of brown adipocyte cells[4]
  • Upregulates uncoupling protein 1 (UCP1) in brown adipose tissue - supports thermogenesis of brown adipose tissue [4,7,8]
  • Promotes whole-body energy expenditure through activation of brown adipose tissue[7,9]
  • Promotes lean body mass[2]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx])[5]

Healthy aging and longevity 

  • Upregulates SIRT-1[2,10]
  • Downregulates the production of advanced glycation end-products (AGEs)[10]

Cardiovascular function

  • Promotes healthy nitric oxide (NO) signaling pathway function[11–14]
  • Upregulates endothelial NO synthase (eNOS)[11]
  • Inhibits phosphodiesterase 5 (PDE-5), the enzyme that cleaves the NO mediator cyclic guanosine monophosphate (cGMP) to 5’GMP[15]
  • Positive effect on NO signaling pathway in cardiac tissue via upregulated cGMP levels[12]
  • Promotes vasodilation via the NO signaling pathway[13,14]

Brain function

  • Acetylcholinesterase inhibition (by the methoxyflavonoid 5,7-dimethoxyflavone [DMF])[16]
  • Neuroprotection from glutamate excitotoxicity (by the methoxyflavonoid 5‐Hydroxy‐3,7,3′,4′‐tetramethoxyflavone)[17]

Reproductive function

  • Inhibits phosphodiesterase-5 (PDE-5)15 and supports relaxation of the corpus cavernosum[18]


REFERENCES

[1] Toda K, et al. Heliyon. 2016;2(5):e00115. doi:10.1016/j.heliyon.2016.e00115
[2] Kim M-B, et al. J Med Food. 2018;21(1):30-38. doi:10.1089/jmf.2017.3989
[3] Toda K, et al. J Nat Med. 2016;70(2):163-172. doi:10.1007/s11418-015-0948-y
[4] Kobayashi H, et al. J Nat Med. 2016;70(1):54-61. doi:10.1007/s11418-015-0936-2
[5] Wattanathorn J, et al. Evid Based Complement Alternat Med. 2012;2012:732816. doi:10.1155/2012/732816
[6] Promthep K, et al. Med Sci Monit Basic Res. 2015;21:100-108. doi:10.12659/MSMBR.894301
[7] Shimada T, et al. Fitoterapia. 2011;82(8):1272-1278. doi:10.1016/j.fitote.2011.08.018
[8] Yoshino S, et al. Food Sci Nutr. 2014;2(6):634-637. doi:10.1002/fsn3.144
[9] Matsushita M, et al. J Nutr Sci Vitaminol . 2015;61(1):79-83. doi:10.3177/jnsv.61.79
[10] Nakata A, et al. Nat Prod Commun. 2014;9(9):1291-1294. PMID: 25918795.
[11] Wattanapitayakul SK, et al. J Ethnopharmacol. 2007;110(3):559-562. doi:10.1016/j.jep.2006.09.037
[12] Weerateerangkul P, et al. J Cardiovasc Pharmacol. 2012;60(3):299-309. doi:10.1097/FJC.0b013e3182609a52
[13] Tep-Areenan P, et al. Phytother Res. 2010;24(10):1520-1525. doi:10.1002/ptr.3164
[14] Tep-Areenan P, et al. Asian Biomed. 2010;4(1):103-111. doi:10.2478/abm-2010-0012
[15] Temkitthawon P, et al. J Ethnopharmacol. 2011;137(3):1437-1441. doi:10.1016/j.jep.2011.08.025
[16] Sawasdee P, et al. Phytother Res. 2009;23(12):1792-1794. doi:10.1002/ptr.2858
[17] Moon H-I, et al. Phytother Res. 2011;25(8):1215-1217. doi:10.1002/ptr.3390
[18] Jansakul C, et al. Eur J Pharmacol. 2012;691(1-3):235-244. doi:10.1016/j.ejphar.2012.07.019

Ziziphus jujuba Seed Extract

ZIZYPHUS JUJUBA COMMON NAME

Jujube | Red date | Chinese date | Semen Ziziphi spinosae | Suanzaoren

TOP BENEFITS OF ZIZYPHUS JUJUBA

Supports sleep*
Supports a calm mood*

WHAT IS ZIZYPHUS JUJUBA?

The Ziziphus jujuba plant is native to many regions in South Asia. The fruits and seeds—in research the seeds are called Ziziphus spinosa, Semen Ziziphi spinosae, or the Chinese name Suanzaoren—have been used in both Korean and Traditional Chinese Medicine (TCM) where they are believed to alleviate stress and were used to calm the mind and spirit. Because of these properties, the seeds are one of the most commonly used herbs for supporting sleep and relaxation in China and other parts of Asia. One of the more popular TCM herbal formulations for sleep and mood support contains five herbs and is called Suanzaoren formula (Suan Zao Ren Tang), [1] and is named for Z. jujuba seeds because of the prominent role they play in the recipe. The main active ingredients are flavonoids (including spinosin and swertisin), saponins (jujubosides), and polysaccharides. [2]. The saponins and flavonoids appear to be the most important compounds for its traditional calming and sleep uses.*

NEUROHACKER’S ZIZYPHUS JUJUBA SOURCING

Ziziphus jujuba seed extract is standardized to contain not less than 2% total saponins. An extract standardized for saponins was selected since these compounds appear to be involved in the sleep support properties of the seeds.

Ziziphus jujuba seed extract is Non-GMO and Vegan

ZIZYPHUS JUJUBA DOSING PRINCIPLES AND RATIONALE

Because preclinical research, especially related to mood and sleep, suggests the potential for adaptogenic properties of Ziziphus jujuba seeds, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. One of our goals when including possible adaptogens in formulas that are intended to be taken long-term, and which will include other adaptogens is to identify a dose range that is likely to support the outcomes we are designing a formula for, and to dose towards the lower end of the range. For sleep support, we based our dosing on a human study that combined a Ziziphus jujuba seed extract (with a similar standardization to what we use) with several European sleep herbs, and chose to include a similar amount to what was used.

ZIZYPHUS JUJUBA KEY MECHANISMS

Stress and sleep

Supports sleep [1,3–5]

Supports sleep time [6–12]

Supports slow-wave sleep (SWS) [11]

Supports healthy behavioral and physiological responses to stress [8,13–16]

Supports stress hormone levels [16]

Brain function

Supports GABAergic neurotransmission [7,12,13,15,17,18]

Supports glutamatergic neurotransmission [18,19]

Supports serotonergic neurotransmission [4,15,18]

Supports noradrenergic neurotransmission [18]

Supports dopaminergic neurotransmission [18]

Downregulates acetylcholinesterase (AChE) activity [20]

Supports choline acetyltransferase (ChAT) [21]

Inhibit adenosine deaminase (ADA) (liver) [22]

Supports glutamic acid decarboxylase (GAD) [12,13]

Supports brain-derived neurotrophic factor (BDNF) [23–25]

Supports neurogenesis [24,26]

Supports long-term potentiation [25,27] 

Supports synaptic transmission [19]

Supports neuroprotective functions [20,21,23,25,27,28]

Supports antioxidant defenses [20,23]

Gut microbiota

Modulates the gut microbiota [29,30]

Modulates gut-immune signaling [17,30]

Modulates microbial metabolism (short-chain fatty acids [SCFAs]) [30]

Synergies

With 5-Hydroxytryptophan (5-HTP) to support sleep [9]


REFERENCES 

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[5] G. Palmieri, P. Contaldi, G. Fogliame, Nat. Sci. Sleep 9 (2017) 163–169.

[6] J.-G. Jiang, X.-J. Huang, J. Chen, Q.-S. Lin, Nat. Prod. Res. 21 (2007) 310–320.

[7] Y. Ma, H. Han, S.-Y. Nam, Y.-B. Kim, J.-T. Hong, Y.-P. Yun, K.-W. Oh, J. Ethnopharmacol. 117 (2008) 318–324.

[8] W.H. Peng, M.T. Hsieh, Y.S. Lee, Y.C. Lin, J. Liao, J. Ethnopharmacol. 72 (2000) 435–441.

[9] J.-X. Cao, Q.-Y. Zhang, S.-Y. Cui, X.-Y. Cui, J. Zhang, Y.-H. Zhang, Y.-J. Bai, Y.-Y. Zhao, J. Ethnopharmacol. 130 (2010) 163–166.

[10] X.S. Fang, J.F. Hao, H.Y. Zhou, L.X. Zhu, J.H. Wang, F.Q. Song, Phytomedicine 17 (2010) 75–80.

[11] L.-E. Wang, X.-Y. Cui, S.-Y. Cui, J.-X. Cao, J. Zhang, Y.-H. Zhang, Q.-Y. Zhang, Y.-J. Bai, Y.-Y. Zhao, Phytomedicine 17 (2010) 404–409.

[12] Y. Ma, H. Han, J.S. Eun, H.C. Kim, J.-T. Hong, K.-W. Oh, Biol. Pharm. Bull. 30 (2007) 1748–1753.

[13] H. Han, Y. Ma, J.S. Eun, R. Li, J.-T. Hong, M.-K. Lee, K.-W. Oh, Pharmacol. Biochem. Behav. 92 (2009) 206–213.

[14] C. Gu, Z. Zhao, X. Zhu, T. Wu, B.H. Lee, Y. Jiao, C.W. Lee, D.H. Jung, C.H. Yang, R. Zhao, S.C. Kim, Evid. Based. Complement. Alternat. Med. 2018 (2018) 2419183.

[15] J. Liu, W.-M. Zhai, Y.-X. Yang, J.-L. Shi, Q.-T. Liu, G.-L. Liu, N. Fang, J. Li, J.-Y. Guo, Pharmacol. Biochem. Behav. 128 (2015) 41–49.

[16] L.B. Li, Y.W. Kim, Y.H. Wang, L. Bai, X.D. Zhu, Z.L. Zhao, C.W. Lee, Y. Jiao, T. Wu, Z.Z. Cai, S.C. Kim, W.G. An, C.H. Yang, G.C. Cui, R.J. Zhao, BMC Complement. Altern. Med. 19 (2019) 147.

[17] X.-X. Wang, G.-I. Ma, J.-B. Xie, G.-C. Pang, J. Ethnopharmacol. 159 (2015) 215–223.

[18] Y. Yan, Q. Li, H.-Z. Du, C.-X. Shen, A.-P. Li, X.-P. Pei, C.-H. Du, X.-M. Qin, Chin. J. Nat. Med. 17 (2019) 551–560.

[19] S.Y. Jo, I.H. Jung, J.H. Yi, T.J. Choi, S. Lee, J.W. Jung, J. Yun, Y.C. Lee, J.H. Ryu, D.H. Kim, J. Ethnopharmacol. 200 (2017) 16–21.

[20] Z. Liu, X. Zhao, B. Liu, A.-J. Liu, H. Li, X. Mao, B. Wu, K.-S. Bi, Y. Jia, Eur. J. Pharmacol. 738 (2014) 206–213.

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Cinnulin PF® Cinnamomum burmannii Bark Extract

Cinnamomum burmannii Bark Extract Common Name

Cinnamon | Indonesian Cassia

Top Benefits of Cinnamon Extract

  • Supports healthy aging*
  • Supports metabolic health*
  • Supports healthy weight*
  • Supports antioxidant defenses*
  • Supports cellular responses*
  • Supports healthy gut microbiota*
  • Supports healthy blood sugar levels*
  • Supports women’s hormone balance*
  • Supports healthy blood pressure*

What is Cinnamon Extract?

Cinnamon is one of the world's oldest spices. Along with pepper and ginger, it was a big part of the spice trade between Asia and Europe. Cinnamon comes from the inner bark of several different tree species from the genus Cinnamomum. The various species of the cinnamon tree are native to India, Sri Lanka, Indonesia, and Burma. While cinnamon species are similar, they don’t produce identical extracts. We opted for Cinnulin PF®—a standardized Cinnamomum burmannii bark extract—because (1) it has undergone human clinical trials, and (2) is monitored to contain not more than 0.7% coumarin, a compound that should only be consumed in low amounts. 

Neurohacker’s Cinnamon Extract Sourcing

Cinnulin PF® is a patented 20:1 water-soluble cinnamon extract from the bark of the Cinnamomum burmannii tree.

Clinically tested and shown to support normal blood sugar levels, insulin signaling pathways, healthy blood pressure, healthy body composition, and women’s hormone balance. *

Standardized to contain not less than 3% doubly linked type-A polymers and not more than 0.7% coumarin.

Produced using a proprietary extraction process called Controlled Polymer Purification Technology (CPPT). This process allows the important, biologically active compounds to be isolated and removes most of the potential toxins from the whole cinnamon.

Non-GMO, Vegan, Certified Kosher

Cinnamon Extract Dosing Principles and Rationale

A dose of 500 mg per day of Cinnulin PF® has been used in clinical trials. This dose, as a sole nutritional intervention, has supported healthy responses in a number of functional health areas. Since we are using the cinnamon extract as part of a stack with other ingredients, we anticipate there being some degree of additive responses. We also do not think cinnamon is a more is better ingredient. Like many plants, cinnamon contains compounds that appear to follow hormetic dosing principles (see Neurohacker Dosing Principles). When this is the case, especially if we intend a formulation to be used long-term, we prefer to be conservative with our dosing. Because of these intersecting principles, we decided to include half the studied dose of Cinnulin PF®.

Cinnamon Extract Key Mechanisms

Metabolism

  • Supports healthy insulin sensitivity (1–8)
  • Upregulates the insulin signaling pathway  (1, 3, 9)
  • Upregulates the glucose transporter GLUT-4 (10–12)
  • Downregulates fat accumulation and blood/liver lipid levels (1, 4, 7–9, 11, 13, 14)
  • Upregulates lean mass (15)
  • Upregulates adiponectin levels (1)

Signaling pathways

  • Upregulates AMP-activated protein kinase (AMPK) signaling (4, 10, 16)
  • Upregulates liver kinase B1 (LKB1)  (10)
  • Upregulates peroxisome proliferator-activated receptor alpha (PPARα) and delta (PPARδ); modulates PPAR gamma (PPARγ) (4, 11, 17)

Antioxidant defenses

  • Downregulates the production of reactive oxygen species and oxidative stress (13, 18, 19)
  • Upregulates antioxidant enzymes (superoxide dismutase [SOD]) (19)
  • Replenishes glutathione (GSH) levels (19)

Cellular signaling

  • Downregulates the expression of proinflammatory molecules (tumor necrosis factor alpha [TNFα], nuclear factor kappa B [NF-κB], interleukin 1β [IL-1β], IL-6) (3, 20, 21)
  • Protects mitochondrial structure and function (22, 23)

Gut microbiota

  • Regulates the composition of the gut microbiota (24, 25)
  • Supports gut barrier function (24)

Healthy aging and longevity 

  • Neuroprotective effects (26)
  • Supports liver function (11)
  • Upregulates heat-shock protein 70 (HSP70) (27)
  • Upregulates SIRT1, SIRT2, and SIRT3 (20, 21)
  • Upregulates uncoupling protein 1 (UCP1) (12, 14)
  • Extends lifespan (Drosophila melanogaster) (27)

REFERENCES

1. B. Qin, M. M. Polansky, R. A. Anderson, Horm. Metab. Res. 42, 187–193 (2010).
2. J. G. Wang et al., Fertil. Steril. 88, 240–243 (2007).
3. B. Qin, H. D. Dawson, N. W. Schoene, M. M. Polansky, R. A. Anderson, Nutrition. 28, 1172–1179 (2012).
4. B. Huang, H. D. Yuan, D. Y. Kim, H. Y. Quan, S. H. Chung, J. Agric. Food Chem. 59, 3666–3673 (2011).
5. M. Hajimonfarednejad et al., Phytother. Res. 32, 276–283 (2018).
6. R. Zare, A. Nadjarzadeh, M. M. Zarshenas, M. Shams, M. Heydari, Clin. Nutr. (2018), doi:10.1016/j.clnu.2018.03.003.
7. A. Borzoei, M. Rafraf, M. Asghari-Jafarabadi, Asia Pac. J. Clin. Nutr. 27, 556–563 (2018).
8. R. A. Anderson et al., Afr. J. Tradit. Complement. Altern. Med. 6, 332–336 (2016).
9. B. Qin, M. M. Polansky, Y. Sato, K. Adeli, R. A. Anderson, J. Nutr. Biochem. 20, 901–908 (2009).
10. Y. Shen et al., PLoS One. 9, e87894 (2014).
11. X. Sheng, Y. Zhang, Z. Gong, C. Huang, Y. Q. Zang, PPAR Res. 2008, 581348 (2008).
12. Y. Shen et al., Biosci. Biotechnol. Biochem. 74, 2418–2425 (2010).
13. A. Borzoei et al., Afr. J. Tradit. Complement. Altern. Med. 8, 128–133 (2018).
14. Y. Tamura, Y. Iwasaki, M. Narukawa, T. Watanabe, J. Nutr. Sci. Vitaminol. . 58, 9–13 (2012).
15. T. N. Ziegenfuss, J. E. Hofheins, R. W. Mendel, J. Landis, R. A. Anderson, J. Int. Soc. Sports Nutr. 3, 45–53 (2006).
16. C. Kopp et al., Int. J. Mol. Sci. 15, 2906–2915 (2014).
17. J.-E. Li et al., Am. J. Chin. Med. 43, 879–892 (2015).
18. A.-M. Roussel, I. Hininger, R. Benaraba, T. N. Ziegenfuss, R. A. Anderson, J. Am. Coll. Nutr. 28, 16–21 (2009).
19. A. S. Sahib, J Intercult Ethnopharmacol. 5, 108–113 (2016).
20. B. Qin, K. S. Panickar, R. A. Anderson, Nutrition. 30, 210–217 (2014).
21. B. Qin, K. S. Panickar, R. A. Anderson, Life Sci. 102, 72–79 (2014).
22. K. Couturier et al., J. Nutr. Biochem. 28, 183–190 (2016).
23. K. S. Panickar, M. M. Polansky, R. A. Anderson, Exp. Neurol. 216, 420–427 (2009).
24. M. Van Hul et al., Am. J. Physiol. Endocrinol. Metab. 314, E334–E352 (2018).
25. Q.-Y. Lu et al., J. Food Sci. 82, 1807–1813 (2017).
26. D. W. Peterson et al., J. Alzheimers. Dis. 17, 585–597 (2009).
27. S. E. Schriner et al., Exp. Gerontol. 60, 220–230 (2014).

Rhodiola rosea Root

Scientific Name:
Rhodiola rosea

COMMON NAME

Roseroot / Golden Root / Arctic Root

BENEFITS

Supports brain function *

Supports resistance to mental fatigue *

Supports stress responses *

Supports neuroprotection *

Supports antioxidant defenses *

Supports cardioprotection*

Supports resistance to physical fatigue

Supports healthy aging *

DESCRIPTION

Rhodiola rosea is an adaptogenic herb with a long history of folk use in Eastern Europe and Asia. Rhodiola rosea contains many biologically active substances, including flavonoids, terpernes, and phenolic compounds; rosavins (rosavin, rosin, and rosarian)  and salidroside are Rhodiola’s major bioactive compounds. As a potent adaptogen, Rhodiola helps to promote homeostasis, resistance to fatigue, and resistance to stress; it also helps to support cognitive performance in contexts of fatigue and stress.[1,2]

KEY MECHANISMS

Brain function

Inhibits monoamine oxidase (MAO) A and B [3,4]

Inhibits acetylcholinesterase [4,5]

Upregulates serotonin levels [6]

Supports neurogenesis [7,8]

Cognitive function

Supports resistance to mental fatigue [9–12]

Supports cognitive performance and attention in contexts of stress and fatigue [9–12]

Stress and mood

Supports stress responses [9–13]

Regulates the levels of stress hormones and other stress response mediators [9,14–17]

Regulates β-endorphin signaling [1,17]

Supports mood [18–20]

Neuroprotection

Protects from cognitive impairments [5,21]

Protects against neurotoxic agents [5,8,21–23]

Protects from ischemia/hypoxia-induced damage [24,25]

Protects from glutamate-induced excitotoxicity [26–28]

Regulates cellular Ca²⁺ homeostasis [24,26]

Antioxidant defenses

Protects from oxidative damage [8,26,29,30]

Downregulates reactive oxygen species (ROS) levels [5,8,22,23,31,32]

Upregulates the levels of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX], glutathione reductase [GR]) [5,21,33,34]

Replenishes glutathione and thioredoxin levels [21,23]

Downregulates NADPH oxidase [5]

 Cardioprotection

Protects cardiac tissue from ischemia/hypoxia-induced damage [35,36]

Protects cardiac tissue from oxidative damage [33]

Physical stamina

Supports resistance to physical fatigue [10]

Supports endurance performance [37]

Supports exercise-induced antioxidant defenses [34]

Healthy aging and longevity

Extends lifespan (Drosophila melanogaster and Caenorhabditis elegans) [31,38,39]

Protects mitochondrial function [23,32,35]

  

REFERENCES

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[2] A. Panossian, G. Wikman, J. Sarris, Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy, Phytomedicine. 17 (2010) 481–493.
[3] D. van Diermen, A. Marston, J. Bravo, M. Reist, P.-A. Carrupt, K. Hostettmann, Monoamine oxidase inhibition by Rhodiola rosea L. roots, J. Ethnopharmacol. 122 (2009) 397–401.
[4]D . van Diermen, A. Marston, J. Bravo, M. Reist, P.A. Carrupt, K. Hostettmann, Inhibition of monoamine oxidase and acetylcholinesterase by Rhodiola rosea L, Planta Med. 74 (2008) PA202.
[5] J. Zhang, Y.-F. Zhen, Pu-Bu-Ci-Ren, L.-G. Song, W.-N. Kong, T.-M. Shao, X. Li, X.-Q. Chai, Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stress and inflammatory mediators in rat hippocampus, Behav. Brain Res. 244 (2013) 70–81.
[6] C. Mannucci, M. Navarra, E. Calzavara, A.P. Caputi, G. Calapai, Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats, Phytomedicine. 19 (2012) 1117–1124.
[7] Q.G. Chen, Y.S. Zeng, Z.Q. Qu, J.Y. Tang, Y.J. Qin, P. Chung, R. Wong, U. Hägg, The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats, Phytomedicine. 16 (2009) 830–838.
[8] Z.-Q. Qu, Y. Zhou, Y.-S. Zeng, Y.-K. Lin, Y. Li, Z.-Q. Zhong, W.Y. Chan, Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat, PLoS One. 7 (2012) e29641.
[9] E.M. Olsson, B. von Schéele, A.G. Panossian, A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue, Planta Med. 75 (2009) 105–112.
[10] A.A. Spasov, G.K. Wikman, V.B. Mandrikov, I.A. Mironova, V.V. Neumoin, A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen, Phytomedicine. 7 (2000) 85–89.
[11] V. Darbinyan, A. Kteyan, A. Panossian, E. Gabrielian, G. Wikman, H. Wagner, Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty, Phytomedicine. 7 (2000) 365–371.
[12] V.A. Shevtsov, B.I. Zholus, V.I. Shervarly, V.B. Vol’skij, Y.P. Korovin, M.P. Khristich, N.A. Roslyakova, G. Wikman, A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work, Phytomedicine. 10 (2003) 95–105.
[13] D. Edwards, A. Heufelder, A. Zimmermann, Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms--results of an open-label study, Phytother. Res. 26 (2012) 1220–1225.
[14] A. Panossian, M. Hambardzumyan, A. Hovhanissyan, G. Wikman, The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol, Drug Target Insights. 2 (2007) 39–54.
[15] A. Panossian, G. Wikman, P. Kaur, A. Asea, Adaptogens stimulate neuropeptide y and hsp72 expression and release in neuroglia cells, Front. Neurosci. 6 (2012) 6.
[16] A. Panossian, G. Wikman, Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity, Pharmaceuticals . 3 (2010) 188–224.
[17] I.B. Lishmanov, Z.V. Trifonova, A.N. Tsibin, L.V. Maslova, L.A. Dement’eva, [Plasma beta-endorphin and stress hormones in stress and adaptation], Biull. Eksp. Biol. Med. 103 (1987) 422–424.
[18] M. Cropley, A.P. Banks, J. Boyle, The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms, Phytother. Res. 29 (2015) 1934–1939.
[19] A. Bystritsky, L. Kerwin, J.D. Feusner, A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD), J. Altern. Complement. Med. 14 (2008) 175–180.
[20]V . Darbinyan, G. Aslanyan, E. Amroyan, E. Gabrielyan, C. Malmström, A. Panossian, Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression, Nord. J. Psychiatry. 61 (2007) 343–348.
[21] Z.-Q. Qu, Y. Zhou, Y.-S. Zeng, Y. Li, P. Chung, Pretreatment with Rhodiola rosea extract reduces cognitive impairment induced by intracerebroventricular streptozotocin in rats: implication of anti-oxidative and neuroprotective effects, Biomed. Environ. Sci. 22 (2009) 318–326.
[22] S.I. Jang, H.O. Pae, B.M. Choi, G.S. Oh, S. Jeong, H.J. Lee, H.Y. Kim, K.J. Kang, Y.G. Yun, Y.C. Kim, H.T. Chung, Salidroside from Rhodiola sachalinensis protects neuronal PC12 cells against cytotoxicity induced by amyloid-beta, Immunopharmacol. Immunotoxicol. 25 (2003) 295–304.
[23] L. Zhang, H. Yu, X. Zhao, X. Lin, C. Tan, G. Cao, Z. Wang, Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells, Neurochem. Int. 57 (2010) 547–555.
[24] Zhang W.-S., Zhu L.-Q., Niu F.-L., Deng R.-C., Ma C.-X., [Protective effects of salidroside on injury induced by hypoxia/hypoglycemia in cultured neurons], Zhongguo Zhong Yao Za Zhi. 29 (2004) 459–462.
[25] Zou Y.-Q., Cai Z.-Y., Mao Y.-F., Li J.-B., Deng X.-M., [Effects of salidroside-pretreatment on neuroethology of rats after global cerebral ischemia-reperfusion], Zhong Xi Yi Jie He Xue Bao. 7 (2009) 130–134.
[26] D.R. Palumbo, F. Occhiuto, F. Spadaro, C. Circosta, Rhodiola rosea extract protects human cortical neurons against glutamate and hydrogen peroxide-induced cell death through reduction in the accumulation of intracellular calcium, Phytother. Res. 26 (2012) 878–883.
[27] X. Chen, J. Liu, X. Gu, F. Ding, Salidroside attenuates glutamate-induced apoptotic cell death in primary cultured hippocampal neurons of rats, Brain Res. 1238 (2008) 189–198.
[28] L.-L. Cao, G.-H. Du, M.-W. Wang, The effect of salidroside on cell damage induced by glutamate and intracellular free calcium in PC12 cells, J. Asian Nat. Prod. Res. 8 (2006) 159–165.
[29] L. Cai, H. Wang, Q. Li, Y. Qian, W. Yao, Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome c release and inactivating of caspase cascade, Acta Biochim. Biophys. Sin. . 40 (2008) 796–802.
[30] X. Chen, Q. Zhang, Q. Cheng, F. Ding, Protective effect of salidroside against H2O2-induced cell apoptosis in primary culture of rat hippocampal neurons, Mol. Cell. Biochem. 332 (2009) 85–93.
[31] S.E. Schriner, A. Abrahamyan, A. Avanessian, I. Bussel, S. Maler, M. Gazarian, M.A. Holmbeck, M. Jafari, Decreased mitochondrial superoxide levels and enhanced protection against paraquat in Drosophila melanogaster supplemented with Rhodiola rosea, Free Radic. Res. 43 (2009) 836–843.
[32] S. Yu, M. Liu, X. Gu, F. Ding, Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation, Cell. Mol. Neurobiol. 28 (2008) 1067–1078.
[33] Y. Zhu, Y.-P. Shi, D. Wu, Y.-J. Ji, X. Wang, H.-L. Chen, S.-S. Wu, D.-J. Huang, W. Jiang, Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway, DNA Cell Biol. 30 (2011) 809–819.
[34] J. Xu, Y. Li, Effects of salidroside on exhaustive exercise‑induced oxidative stress in rats, Mol. Med. Rep. 6 (2012) 1195–1198.
[35] H. Zhong, H. Xin, L.-X. Wu, Y.-Z. Zhu, Salidroside attenuates apoptosis in ischemic cardiomyocytes: a mechanism through a mitochondria-dependent pathway, J. Pharmacol. Sci. 114 (2010) 399–408.
[36] T. Wu, H. Zhou, Z. Jin, S. Bi, X. Yang, D. Yi, W. Liu, Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins, Eur. J. Pharmacol. 613 (2009) 93–99.
[37] K. De Bock, B.O. Eijnde, M. Ramaekers, P. Hespel, Acute Rhodiola rosea intake can improve endurance exercise performance, Int. J. Sport Nutr. Exerc. Metab. 14 (2004) 298–307.
[38] M. Jafari, J.S. Felgner, I.I. Bussel, T. Hutchili, B. Khodayari, M.R. Rose, C. Vince-Cruz, L.D. Mueller, Rhodiola: a promising anti-aging Chinese herb, Rejuvenation Res. 10 (2007) 587–602.
[39] F.A.C. Wiegant, S. Surinova, E. Ytsma, M. Langelaar-Makkinje, G. Wikman, J.A. Post, Plant adaptogens increase lifespan and stress resistance in C. elegans, Biogerontology. 10 (2009) 27–42.

Lion’s Mane

Scientific Name:
Hericium erinaceus

Overview:
Lion’s Mane is a mushroom with neuroprotective and nootropic effects. Lion’s Mane can improve memory and reasoning.

Scientific Name:
Hericium erinaceus

Mechanisms:

  • Increases NGF levels in the brain – enhanced neuronal growth, regeneration and synaptic plasticity[1]
  • Improves myelination – enhanced neuronal communication and nerve regeneration[2]
  • Increases long-term synaptic potentiation – improved memory[3,4]
  • Decreases glutamatergic transmission – decreased neuronal excitability and excitotoxicity[3,4]
  • Protects neurons from endoplasmic reticulum stress[3,4]
  • Anxiolytic[5]
  • Anti-inflammatory effects[6]
References

[1] Lai PL, et al (2013). Neurotrophic properties of the Lion’s mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Int J Med Mushrooms, 15(6):539-54. doi: 10.1615/IntJMedMushr.v15.i6.30
[2] Kolotushkina EV, et al (2003). The influence of Hericium erinaceus extract on myelination process in vitro. Fiziol Zh, 49(1):38-45. PMID: 12675022
[3] Phan CW, et al (2015). Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol, 35(3):355-68. doi: 10.3109/07388551.2014.887649
[4] Sabaratnam V, et al (2013). Neuronal health – can culinary and medicinal mushrooms help? J Tradit Complement Med, 3(1):62-8. doi: 10.4103/2225-4110.106549
[5] Nagano M, et al (2010). Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res, 31(4):231-7. doi: 10.2220/biomedres.31.231
[6] Geng Y, et al (2014). Anti-inflammatory activity of mycelial extracts from medicinal mushrooms. Int J Med Mushrooms, 16(4):319-25. doi: 10.1615/IntJMedMushrooms.v16.i4.20

Artichoke Stem and Leaf Extract

Scientific Name:
Cynara cardunculus

Overview:
Artichoke (Cynara cardunculus) is a plant that contains cynarin, having nootropic effects. Cynarin can significantly improve memory and executive function.

Scientific Name:
Cynara cardunculus

Mechanisms:

  • Artichoke extract contains polyphenols with antioxidant action and cynarin, its main biologically active compound[1]
  • Increases long-term synaptic potentiation – improved memory[2]
  • Enhances working memory, short-term memory, memory consolidation, and memory recall[2]
  • Synergistic with forskolin in increasing cAMP levels – inhibits phosphodiesterase-4[3]
  • Enhances logic, mathematical, and practical reasoning[4]
References

[1] Li H, et al (2004). Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells. J Pharmacol Exp Ther, 310(3):926-32. doi: 10.1124/jpet.104.066639
[2] Barad M, et al (1998). Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc Natl Acad Sci U S A, 95(25):15020-5. PMID: 9844008
[3] Yu MC, et al (2010). Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [3H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia. Eur J Pharmacol, 627(1-3):269-75. doi: 10.1016/j.ejphar.2009.10.031
[4] Reneerkens OA, et al (2009). Selective phosphodiesterase inhibitors: a promising target for cognition enhancement. Psychopharmacology (Berl), 202(1-3):419-43. doi: 10.1007/s00213-008-1273-x

Gynostemma

Scientific Name:
Gynostemma pentaphyllum

Overview:
Gynostemma is an herb with neuroprotective and adaptogenic effects. Gynostemma can improve memory

Scientific Name:
Gynostemma pentaphyllum

Mechanisms:

  • Increases the levels of superoxide dismutase (SOD), glutathione and other anti-oxidants – neuroprotective effect[1]
  • Maintains optimal homeostasis and improves resistance to stress – adaptogenic effect[2]
  • Improves memory as a consequence of antioxidant mechanisms[3]
  • Anti-inflammatory effects through NF-kB inhibition
  • Anti-aging effect
References

[1] Zhang GL, et al (2011). Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic activation. Behav Pharmacol, 22(7):633-44. doi: 10.1097/FBP.0b013e32834afef9
[2] Zhao TT, et al (2015). Ameliorating effects of gypenosides on chronic stress-induced anxiety disorders in mice. BMC Complement Altern Med, 15:323. doi: 10.1186/s12906-015-0856-4
[3] Schild L, et al (2009). Protection of hippocampal slices against hypoxia/hypoglycemia injury by a Gynostemma pentaphyllum extract. Phytomedicine, 16(8):734-43. doi: 10.1016/j.phymed.2009.03.006
[4] Aktan F, et al (2003). Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression. Nitric Oxide, 8(4):235-42. doi: 10.1016/S1089-8603(03)00032-6

Ginkgo biloba Leaf Extract

Scientific Name:
Ginkgo biloba

Overview:
Ginkgo biloba is a plant with neuroprotective, nootropic and adaptogenic effects. Ginkgo biloba can delay aging, improving memory and attention.

Scientific Name:
Ginkgo biloba

Mechanisms:

  • Contains flavonoid glycosides such as quercetin, and terpene lactones such as ginkgolides and bilobalides – main bioactive substances[1]
  • Increases dopamine, acetylcholine and noradrenaline levels[2,3]
  • Modulates histaminergic neurotransmission improving learning and memory[4]
  • Increases BDNF levels and promotes neurogenesis and neuronal survival[5]
  • Improves cerebral blood flow by inhibiting the platelet activating factor (PAF) receptor[6]
  • Delays cognitive decline and improves short term memory and free recall[7]
  • Reduces stress and anxiety and decreases corticosterone levels – adaptogenic effect[8]
  • Has antioxidant and anti-inflammatory effects and preserves mitochondrial function – anti-aging effect[9]
References

[1] van Beek TA (2002). Chemical analysis of Ginkgo biloba leaves and extracts. J Chromatogr A, 16;967(1):21-55. doi: 10.1016/S0021-9673(02)00172-3
[2] Ponto LL, Schultz SK (2003). Ginkgo biloba extract: review of CNS effects. Ann Clin Psychiatry, 15(2):109-19. doi: 10.1023/A:1024688326023
[3] Ahlemeyer B, Krieglstein J (2003). Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci, 60(9):1779-92. doi: 10.1007/s00018-003-3080-1
[4] Yamamoto Y, et al (2007). Ginkgo biloba extract improves spatial memory in rats mainly but not exclusively via a histaminergic mechanism. Brain Res, 1129(1):161-5. doi: 10.1016/j.brainres.2006.08.102
[5] Tchantchou F, et al (2009). Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J Alzheimers Dis. 2009;18(4):787-98. doi: 10.3233/JAD-2009-1189
[6] Liao HJ, et al (2011). Two new ginkgolides from the leaves of Ginkgo biloba. Planta Med, 77(16):1818-21. doi: 10.1055/s-0030-1271153
[7] Kanowski S, et al (1996). Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry, 29(2):47-56. doi: 10.1016/S0944-7113(97)80021-9
[8] Rapin JR, et al (1994). Demonstration of the “anti-stress” activity of an extract of Ginkgo biloba (EGb 761) using a discrimination learning task. Gen Pharmacol, 25(5):1009-16. doi: 10.1016/0306-3623(94)90111-2
[9] Eckert A, et al (2003). Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress. Pharmacopsychiatry, 36 Suppl 1:S15-23. doi: 10.1055/s-2003-40449

Bacopa monnieri Leaf Extract

Scientific Name:
Bacopa monnieri

Overview:
Studies indicate that Bacopa monnieri has neuroprotective, nootropic and adaptogenic effects. Research shows that it can improve memory formation and recall.

Scientific Name:
Bacopa monnieri

Mechanisms:

  • Bacosides are the active ingredients in Bacopa monnieri[1]
  • Inhibits acetylcholinesterase, activates choline acetyltransferase – increased levels of acetylcholine[1]
  • Increases neurite branching and proliferation – improves synaptic communication and memory[1]
  • Modulates the dopaminergic and serotonergic systems – mood enhancer[3]
  • Modulates the levels of superoxide dismutase (SOD) and oxidative damage from metals in the brain – protective against neurodegeneration[4]
  • Anxiolytic and analgesic effects[5,6]
  • Reduce the levels of the stress marker HSP70 in the brain – adaptogenic effect[7]
  • Synergistic with curcumin and EGCG[8]
References

[1] Aguiar S, Borowski T (2013). Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res, 16(4):313-26. doi: 10.1089/rej.2013.1431
[2] Sivaramakrishna, C, et al (2005). Triterpenoid glycosides from Bacopa monnieri. Phytochemistry, 66: 2719–2728. doi: 10.1016/j.phytochem.2005.09.016
[3] Rauf K, et al (2012). Effect of acute and sub-chronic use of Bacopa monnieri on dopamine and serotonin turnover in mice whole brain. AJPP. 2012;6:2767–2774. doi: 10.5897/AJPP12.244
[4] Chowdhuri DK, et al (2002). Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res, 16(7):639-45. doi: 10.1002/ptr.1023
[5] Chatterjee M, et al (2010). Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice. Indian J Exp Biol, 48(3):306-13. PMID: 21046986
[6] Bhaskar M, Jagtap AG (2011). Exploring the possible mechanisms of action behind the antinociceptive activity of Bacopa monniera. Int J Ayurveda Res, 2(1):2-7. doi: 10.4103/0974-7788.83173
[7] Anbarasi K, et al (2006). Cigarette smoking induces heat shock protein 70 kDa expression and apoptosis in rat brain: Modulation by bacoside A. Neuroscience, 138(4):1127-35. doi: 10.1016/j.neuroscience.2005.11.029
[8] Velmurugan K, et al (2009). Synergistic induction of heme oxygenase-1 by the components of the antioxidant supplement Protandim. Free Radic Biol Med, 46(3):430-40. doi: 10.1016/j.freeradbiomed.2008.10.050

Mucuna pruriens Seed

Scientific Name:
Mucuna pruriens, L-3,4-dihydroxyphenylalanine

Overview:
Mucuna pruriens is a bean with neuroprotective and adaptogenic effects. Mucuna pruriens is a mood enhancer and increases focus and motivation.

Scientific Name:
Mucuna pruriens, L-3,4-dihydroxyphenylalanine

Mechanisms:

  • L-DOPA is its main active substance[1]
  • Regulates the levels of dopamine, noradrenaline, adrenaline and serotonin in the brain[2]
  • Synergistic with P5P in the production of dopamine[3]
  • Anxiolytic effects[4]
  • Reduces the production of cortisol in response to stress[5]
  • Decreases the levels of free radicals, reactive oxygen species, neurotoxins and heavy metal poisoning[6]
  • Increases the production of growth hormone and melanin[7]
References

[1] Pulikkalpura H, et al (2015). Levodopa in Mucuna pruriens and its degradation. Sci Rep, 5:11078. doi: 10.1038/srep11078
[2] Misu Y, et al (1996). Neurobiology of L-DOPAergic systems. Prog Neurobiol, 49(5):415-54. doi: 10.1016/0301-0082(96)00025-1
[3] Das Gupta V, Gupta A (1980). Effect of pyridoxal 5-phosphate on carbidopa and decarboxylation of levodopa. J Pharm Sci, 69(10):1145-8. doi: 10.1002/jps.2600691005
[4] Rana DG, Galani VJ (2014). Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu, 35(1):90-7. doi: 10.4103/0974-8520.141949
[5] Shukla KK, et al (2007). Mucuna pruriens Reduces Stress and Improves the Quality of Semen in Infertile Men. Evid Based Complement Alternat Med, 7(1):137-44. doi: 10.1093/ecam/nem171
[6] Lampariello LR, et al (2012). The Magic Velvet Bean of Mucuna pruriens. J Tradit Complement Med, 2(4):331-9. PMID: 24716148
[7] Chihara K, et al (1986). L-dopa stimulates release of hypothalamic growth hormone-releasing hormone in humans. J Clin Endocrinol Metab, 62(3):466-73. doi: 10.1210/jcem-62-3-466

Coleus forskohlii Root

Scientific Name:
Forskolin from Coleus Forskohlii

Overview:
Forskolin is a labdane diterpene and the main bioactive compound in Coleus forskohlii, having nootropic and adaptogenic effects. Forskolin improves learning, memory and mental stamina.

Scientific Name:
Forskolin from Coleus Forskohlii

Mechanisms:

  • Forskolin increases intracellular levels of cAMP through adenylate cyclase activation – increased responsiveness to extracellular stimuli[1]
  • Improves stress response by improving cell communication in the HPA axis – adaptogenic effect[2]
  • Synergistic with artichoke extract in increasing cAMP levels[1]
  • Inhibits acetylcholinesterase – increased acetylcholine levels[3]
  • Decreases fatigue[4]
  • Anti-inflammatory effects[5]
References

[1] Litosch I, Hudson TH, Mills I, Li SY, Fain JN (1982). Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes. Mol Pharmacol, 22(1):109-15. PMID: 6289066
[2] Kumari M, Cover PO, Poyser RH, Buckingham JC (1997). Stimulation of the hypothalamo-pituitary-adrenal axis in the rat by three selective type-4 phosphodiesterase inhibitors: in vitro and in vivo studies. Br J Pharmacol, 121(3):459-68. doi: 10.1038/sj.bjp.0701158
[3] Yang QR, Wu HZ, Wang XM, Zou GA, Liu YW (2006). Three new diterpenoids from Coleus forskohlii Briq. J Asian Nat Prod Res, 8(4):355-60. doi: 10.1080/10286020500172236
[4] Henderson S, et al (2005). Effects of coleus forskohlii supplementation on body composition and hematological profiles in mildly overweight women. J Int Soc Sports Nutr, 2:54-62. doi: 10.1186/1550-2783-2-2-54
[5] Menon DB, Latha K (2011). Phytochemical Screening and In vitro Anti-inflammatory Activity of the Stem of Coleus forskohlii. 3(23):75-79. doi: 10.5530/pj.2011.23.11