Nootropics

Potent psychoactive and neuroactive chemicals that play key roles in modulating receptor sites, synaptic enzymes, membrane structures, cerebral perfusion, biogenic processes, neuroendocrine regulation and more.

Cognizin® Citicoline

Scientific Name:
Cytidine diphosphocholine

EnXtra® Alpinia Galanga

COMMON NAME

Greater Galangal | Thai Ginger | Siamese Ginger

TOP BENEFITS OF EnXtra^®

Sharpens alertness and focus*

Amplifies caffeine’s nootropic benefits*

Supports brain and cognitive function*

WHAT IS EnXtra^®?

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 human studies, EnXtra^® has been complementary to 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 EnXtra^® 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. 

EnXtra® FORMULATING 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 a serving that is consistent with the studied amount in the human clinical studies.*

ALPINIA GALANGA KEY MECHANISMS

Supports cognitive function*

Supports mental alertness [2]

Supports attention [3]

Supports memory [4,5]

Supports brain function*

Supports neuroprotective functions [4–6]

CNS stimulant activity [7]

Supports locomotor activity and motor coordination [7]

Influences acetylcholinesterase (AChE) levels/activity in the brain [4,5]

Influences monoamine oxidase (MAO) A and B levels/activity in the brain [5]

Supports antioxidant defenses*

Supports antioxidant defenses in the brain [4–6,8]

Replenishes glutathione (GSH) levels [8]

Counters lipid peroxidation [6,8]

Other actions*

Supports healthy cardiometabolic parameters [8,9]

Supports immune system activation [10]

Complementary ingredients*

Caffeine — supports sustained attention [2]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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.

Alpha-glycerophosphocholine (Alpha-GPC)

Scientific Name:
Alpha-glycerophosphocholine

Celastrus Paniculatus Seed Extract

Scientific Name:
Celastrus paniculatus Willd

Polygala tenuifolia Root Extract

COMMON NAME

Polygalae Radix | Yuan zhi | Onji

TOP BENEFITS OF POLYGALA TENUIFOLIA

Supports cognitive function*

Supports a healthy stress response*

Supports sleep*

Supports mood*

WHAT IS POLYGALA TENUIFOLIA?

In Traditional Chinese Medicine, Polygala tenuifolia root is one of the most used herbs to support the brain and central nervous system. Traditionally it was often used to reduce forgetfulness and support brain performance during aging (i.e., it’s what we’d consider a nootropic today). It was also commonly used in formulas to support sleep and promote a calmer, more balanced mood. Preclinical research suggests it supports brain protection and repair processes and molecules (such as BDNF and NGF), counters chronic stress, supports sleep, and influences both adenosine signaling—a molecule involved in the sleep homeostatic drive—and GABA signaling—a neurotransmitter involved with relaxation at night and sleep. The roots have several bioactive compounds thought to be relatively unique to this plant including tenuigenin, tenuifolin, yuanzhi-1, tenuifolisides, and tenuifolioses.*

NEUROHACKER’S POLYGALA TENUIFOLIA SOURCING

Polygala tenuifolia root extract is a 10:1 extract, which means that 10 parts of the root are used to create 1 part of the extract. This concentrates the active compounds, so less of the herb is needed.

Polygala tenuifolia root extract is Non-GMO and Vegan.

POLYGALA TENUIFOLIA FORMULATING PRINCIPLES AND RATIONALE

Because preclinical research suggests the potential for adaptogenic properties of Polygala tenuifolia, we consider formulation 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. Based on human studies and traditional uses, we’d consider the serving range for concentrated extracts to be about 100-300 mg daily (about 1-3 grams of crude root powder). Our goal with P. tenuifolia, as with all ingredient choices, is to select the appropriate serving keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogens and nootropic extracts, we are likely to choose an amount of P. tenuifolia towards the lower end of the range.*

POLYGALA TENUIFOLIA KEY MECHANISMS

Supports brain function*

Supports learning and memory [1–4]

Supports sleep [5–7]

Supports glutamate decarboxylase (GAD) activity [8]

Supports GABA-Glutamate signaling [6,8–10]

Supports adenosine signaling [11]

Supports adrenergic signaling [3,5,6]

Supports dopamine signaling [3,12]

Influences acetylcholinesterase (AChE) activity [3,4,13]

Influences monoamine oxidase (MAO) activity [4]

Supports brain-derived neurotrophic factor (BDNF) [14,15]

Supports synaptic transmission in the hippocampus [15]

Supports long-term potentiation (LTP)/synaptic plasticity [13,15]

Supports the proliferation and differentiation of neural stem cells [16,17]

Supports neuroprotective functions [15,18–23]

Supports antioxidant defenses [4,13,20,24]

Supports healthy stress responses*

Supports healthy behavioral and physiological responses to stress [7,10,14]

Supports a healthy gut microbiota*

Supports the composition of the gut microbiota [25]

Supports healthy immune function*

Supports adaptive immunity [26]

Supports macrophage functions [27]

Promotes healthy aging and longevity*

Supports mitochondrial function [22]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES 

[1] J.-Y. Lee, K.Y. Kim, K.Y. Shin, B.Y. Won, H.Y. Jung, Y.-H. Suh, Neurosci. Lett. 454 (2009) 111–114.

[2] K.Y. Shin, J.-Y. Lee, B.Y. Won, H.Y. Jung, K.-A. Chang, S. Koppula, Y.-H. Suh, Neurosci. Lett. 465 (2009) 157–159.

[3] H. Zhang, T. Han, L. Zhang, C.-H. Yu, D.-G. Wan, K. Rahman, L.-P. Qin, C. Peng, Phytomedicine 15 (2008) 587–594.

[4] Z. Li, Y. Liu, L. Wang, X. Liu, Q. Chang, Z. Guo, Y. Liao, R. Pan, T.-P. Fan, Evid. Based. Complement. Alternat. Med. 2014 (2014) 392324.

[5] K. Kawashima, D. Miyako, Y. Ishino, T. Makino, K.-I. Saito, Y. Kano, Biol. Pharm. Bull. 27 (2004) 1317–1319.

[6] Q. Cao, Y. Jiang, S.-Y. Cui, P.-F. Tu, Y.-M. Chen, X.-L. Ma, X.-Y. Cui, Y.-L. Huang, H. Ding, J.-Z. Song, B. Yu, Z.-F. Sheng, Z.-J. Wang, Y.-P. Xu, G. Yang, H. Ye, X. Hu, Y.-H. Zhang, Phytomedicine 23 (2016) 1797–1805.

[7] Y. Yao, M. Jia, J.-G. Wu, H. Zhang, L.-N. Sun, W.-S. Chen, K. Rahman, Pharm. Biol. 48 (2010) 801–807.

[8] C.-I. Lee, J.-Y. Han, J.T. Hong, K.-W. Oh, Arch. Pharm. Res. 36 (2013) 1244–1251.

[9] C.-Y. Chen, X.-D. Wei, C.-R. Chen, J. Pharmacol. Sci. 131 (2016) 1–5.

[10] I.-J. Shin, S.U. Son, H. Park, Y. Kim, S.H. Park, K. Swanberg, J.-Y. Shin, S.-K. Ha, Y. Cho, S.-Y. Bang, J.-H. Lew, S.-H. Cho, S. Maeng, PLoS One 9 (2014) e88617.

[11] E.-J. Shin, K.-W. Oh, K.-W. Kim, Y.S. Kwon, J.H. Jhoo, W.-K. Jhoo, J.-Y. Cha, Y.K. Lim, I.S. Kim, H.-C. Kim, Life Sci. 75 (2004) 2751–2764.

[12] H.-L. Yuan, B. Li, J. Xu, Y. Wang, Y. He, Y. Zheng, X.-M. Wang, CNS Neurosci. Ther. 18 (2012) 584–590.

[13] J.-N. Huang, C.-Y. Wang, X.-L. Wang, B.-Z. Wu, X.-Y. Gu, W.-X. Liu, L.-W. Gong, P. Xiao, C.-H. Li, Behav. Brain Res. 246 (2013) 111–115.

[14] Y. Hu, P. Liu, D.-H. Guo, K. Rahman, D.-X. Wang, T.-T. Xie, Pharm. Biol. 48 (2010) 794–800.

[15] W. Xue, J.-F. Hu, Y.-H. Yuan, J.-D. Sun, B.-Y. Li, D.-M. Zhang, C.-J. Li, N.-H. Chen, Acta Pharmacol. Sin. 30 (2009) 1211–1219.

[16] H.-J. Park, K. Lee, H. Heo, M. Lee, J.W. Kim, W.W. Whang, Y.K. Kwon, H. Kwon, Phytother. Res. 22 (2008) 1324–1329.

[17] Y. Chen, X. Huang, W. Chen, N. Wang, L. Li, Neurochem. Res. 37 (2012) 771–777.

[18] Y. Ikeya, S. Takeda, M. Tunakawa, H. Karakida, K. Toda, T. Yamaguchi, M. Aburada, Biol. Pharm. Bull. 27 (2004) 1081–1085.

[19] X.-L. Sun, H. Ito, T. Masuoka, C. Kamei, T. Hatano, Biol. Pharm. Bull. 30 (2007) 1727–1731.

[20] X. Li, Y. Sun, Y. Wei, L. Zhou, L. Liu, P. Yin, Y. Liu, S. Wu, J. Li, C. Lu, Curr. Neurovasc. Res. 15 (2018) 94–102.

[21] T. Kuboyama, K. Hirotsu, T. Arai, H. Yamasaki, C. Tohda, Front. Pharmacol. 8 (2017) 805.

[22] L. Wang, G.F. Jin, H.H. Yu, X.H. Lu, Z.H. Zou, J.Q. Liang, H. Yang, Food Funct. 10 (2019) 7453–7460.

[23] J.-H. Park, J.S. Kim, D.S. Jang, S.-M. Lee, Am. J. Chin. Med. 34 (2006) 115–123.

[24] P. Liu, Y. Hu, D.-H. Guo, B.-R. Lu, K. Rahman, L.-H. Mu, D.-X. Wang, Pharm. Biol. 48 (2010) 828–833.

[25] C.-C. Wang, J.-H. Yen, Y.-C. Cheng, C.-Y. Lin, C.-T. Hsieh, R.-J. Gau, S.-J. Chiou, H.-Y. Chang, Food Nutr. Res. 61 (2017) 1379861.

[26] T. Nagai, Y. Suzuki, H. Kiyohara, E. Susa, T. Kato, T. Nagamine, Y. Hagiwara, S. Tamura, T. Yabe, C. Aizawa, H. Yamada, Vaccine 19 (2001) 4824–4834.

[27] K.-S. Kim, D.-S. Lee, G.-S. Bae, S.-J. Park, D.-G. Kang, H.-S. Lee, H. Oh, Y.-C. Kim, Eur. J. Pharmacol. 721 (2013) 267–276.

Gotu Kola ( Centella asiatica ) Whole Herb Extract

GOTU KOLA COMMON NAME

Gotukola | Indian Pennywort | Asiatic Pennywort

TOP BENEFITS OF GOTU KOLA

Supports a calm mood and feelings of contentment*

Supports mental alertness and attention*

Supports a healthy stress response*

Supports circulation*

WHAT IS GOTU KOLA?

In Ayurvedic medicine, gotu kola (Centella asiatica; synonym is Hydrocotyle asiatica) is considered to be a mental rejuvenator (medhya Rasayana), where it was traditionally used as a tonic herb to counter mental fatigue and improve thinking. It was thought to be particularly useful during times of increased mental demands. Other traditional uses included support of blood/circulation, skin regeneration, and general longevity. Modern science has upheld some of this reputation—gotu kola is a nootropic and supports brain repair and rejuvenation processes. It also supports healthy veins and circulation. Gotu kola, unlike many other nootropics that are best taken only at the beginning of the day, is a great fit at the end of a busy day because it is calming and supports repair and rejuvenation processes. Gotu kola contains several characteristic bioactive compounds, including asiaticoside, asiatic acid, madecassic acid, madecassoside, and centelloside. Gotu kola also contains other compounds with biological activity found in other plants such as ursolic acid, rosmarinic acid, and the flavonoids apigenin and rutin [1].*

NEUROHACKER’S GOTU KOLA SOURCING

Gotu kola is a whole herb extract. It is standardized to contain not less than 10% asiaticosides, since this group of active compounds are thought to be the main bioactives.

Gotu kola is Non-GMO and Vegan.

GOTU KOLA FORMULATING PRINCIPLES AND RATIONALE

Because gotu kola 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. Based on human studies, where extracts standardized for one or more of gotu kola’s asiaticosides have been used, we consider the target range of asiaticosides to be between about 12.5mg to 50mg for nootropic and mood purposes. The mg amount of gotu kola used will depend on its standardization and will be chosen to deliver an amount of asiaticosides within this range. Our goal with gotu kola, as with all ingredient choices, is to select the appropriate serving keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogens and nootropic extracts, we are likely to use less gotu kola than if the only herbal adaptogen/nootropic we were using was gotu kola.*

GOTU KOLA KEY MECHANISMS

Supports healthy mood and stress responses*

Supports a calm mood [2–8]

Supports healthy behavioral and physiological responses to stress [8]

Supports brain function*

Supports working memory [4]

Supports learning and memory [9–15]

Supports executive function [10,11]

Supports glutamate decarboxylase (GAD) activity [16] 

Supports GABAergic neurotransmission [17]

Supports GABA receptor agonist actions [asiatic acid] [18–20] 

Supports glutamatergic AMPA receptors [9]

Downregulates acetylcholinesterase (AChE) [14,18]

Supports hippocampal synaptic density [11]

Supports the expression of synaptic markers in the hippocampus and frontal cortex [21]

Supports brain mitochondrial function [10,11,14,21,22]

Supports brain-derived neurotrophic factor (BDNF) [12,13,23,24]

Supports NMDA receptors [24] 

Supports hippocampal long-term potentiation [24]

Supports Nrf2 signaling in the brain [10,11,21,22]

Supports antioxidant defenses [7,10,11,14,21,22,25]

Supports neuroprotective functions [26]

Supports healthy immune system function*

Supports innate immunity [27]

Supports adaptive immunity [28,29]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

[1]K.J. Gohil, J.A. Patel, A.K. Gajjar, Indian J. Pharm. Sci. 72 (2010) 546–556.

[2]U. Jana, T.K. Sur, L.N. Maity, P.K. Debnath, D. Bhattacharyya, Nepal Med. Coll. J. 12 (2010) 8–11.

[3]P. Puttarak, P. Dilokthornsakul, S. Saokaew, T. Dhippayom, C. Kongkaew, R. Sruamsiri, A. Chuthaputti, N. Chaiyakunapruk, Sci. Rep. 7 (2017) 10646.

[4]J. Wattanathorn, L. Mator, S. Muchimapura, T. Tongun, O. Pasuriwong, N. Piyawatkul, K. Yimtae, B. Sripanidkulchai, J. Singkhoraard, J. Ethnopharmacol. 116 (2008) 325–332.

[5]J. Bradwejn, Y. Zhou, D. Koszycki, J. Shlik, J. Clin. Psychopharmacol. 20 (2000) 680–684.

[6]K.V. Mitha, S. Yadav, B. Ganaraja, Indian J. Physiol. Pharmacol. 60 (2016) 167–173.

[7]P. Chanana, A. Kumar, Phytother. Res. 30 (2016) 671–680.

[8]A. Wanasuntronwong, M.H. Tantisira, B. Tantisira, H. Watanabe, J. Ethnopharmacol. 143 (2012) 579–585.

[9]N.A. Binti Mohd Yusuf Yeo, S. Muthuraju, J.H. Wong, F.R. Mohammed, M.H. Senik, J. Zhang, S.R. Yusof, H. Jaafar, M.L. Adenan, H. Mohamad, T.S. Tengku Muhammad, J.M. Abdullah, Brain Behav. 8 (2018) e01093.

[10]N.E. Gray, J.A. Zweig, M. Caruso, J.Y. Zhu, K.M. Wright, J.F. Quinn, A. Soumyanath, Mol. Cell. Neurosci. 93 (2018) 1–9.

[11]N.E. Gray, J.A. Zweig, M. Caruso, M.D. Martin, J.Y. Zhu, J.F. Quinn, A. Soumyanath, Brain Behav. 8 (2018) e01024.

[12]D.C.R. Sari, N. Arfian, U. Tranggono, W.A.W. Setyaningsih, M.M. Romi, N. Emoto, Iran. J. Basic Med. Sci. 22 (2019) 1218–1224.

[13]G. Sbrini, P. Brivio, M. Fumagalli, F. Giavarini, D. Caruso, G. Racagni, M. Dell’Agli, E. Sangiovanni, F. Calabrese, Nutrients 12 (2020).

[14]A. Kumar, A. Prakash, S. Dogra, Int. J. Alzheimers. Dis. 2011 (2011) 347569.

[15]M.N. Nasir, M. Habsah, I. Zamzuri, G. Rammes, J. Hasnan, J. Abdullah, J. Ethnopharmacol. 134 (2011) 203–209.

[16]R. Awad, D. Levac, P. Cybulska, Z. Merali, V.L. Trudeau, J.T. Arnason, Canadian Journal of Physiology and Pharmacology 85 (2007) 933–942.

[17]T.K. Chatterjee, A. Chakraborty, M. Pathak, G.C. Sengupta, Indian J. Exp. Biol. 30 (1992) 889–891.

[18]M.N. Nasir, J. Abdullah, M. Habsah, R.I. Ghani, G. Rammes, Phytomedicine 19 (2012) 311–316.

[19]T.E. Ceremuga, D. Valdivieso, C. Kenner, A. Lucia, K. Lathrop, O. Stailey, H. Bailey, J. Criss, J. Linton, J. Fried, A. Taylor, G. Padron, A.D. Johnson, AANA J. 83 (2015) 91–98.

[20]K. Hamid, I. Ng, V.J. Tallapragada, L. Váradi, D.E. Hibbs, J. Hanrahan, P.W. Groundwater, Chem. Biol. Drug Des. 88 (2016) 386–397.

[21]N.E. Gray, C.J. Harris, J.F. Quinn, A. Soumyanath, J. Ethnopharmacol. 180 (2016) 78–86.

[22]N.E. Gray, J.A. Zweig, D.G. Matthews, M. Caruso, J.F. Quinn, A. Soumyanath, Oxid. Med. Cell. Longev. 2017 (2017) 7023091.

[23]M. Ar Rochmah, I.M. Harini, D.E. Septyaningtrias, D.C.R. Sari, R. Susilowati, Biomed Res. Int. 2019 (2019) 2649281.

[24]Y. Boondam, P. Songvut, M.H. Tantisira, S. Tapechum, K. Tilokskulchai, N. Pakaprot, Sci. Rep. 9 (2019) 8404.

[25]N. Haleagrahara, K. Ponnusamy, J. Toxicol. Sci. 35 (2010) 41–47.

[26]S. Chen, Z.-J. Yin, C. Jiang, Z.-Q. Ma, Q. Fu, R. Qu, S.-P. Ma, Pharmacol. Biochem. Behav. 122 (2014) 7–15.

[27]M.G. Jayathirtha, S.H. Mishra, Phytomedicine 11 (2004) 361–365.

[28]D. Arora, M. Kumar, S.D. Dubey, U. Sings, Anc. Sci. Life 22 (2002) 42–48.

[29]K. Punturee, C.P. Wild, W. Kasinrerk, U. Vinitketkumnuen, Asian Pac. J. Cancer Prev. 6 (2005) 396–400.

Caffeine

Uridine Monophosphate

Scientific Name:
Uridine Monophosphate, (UMP)

Coffeeberry® Whole Coffee Fruit Extract

COMMON NAME

Coffee Fruit | Coffee Cherry | Coffee Berry

TOP BENEFITS OF COFFEEBERRY^®

Supports cognitive performance*

Supports exercise performance*

Supports mood*

WHAT IS COFFEEBERRY^®?

Coffeeberry^® is made from organic coffee fruits, which are often called coffee cherries. Like cherries, coffee plants produce soft red fruits surrounding a pit or hard seed. The seed (or coffee “bean”) is roasted to make coffee. But it’s the fruit that is being used to make Coffeeberry^®. Similar to many fruits, coffee cherries are high in polyphenols. And like coffee beans, they also contain caffeine. There are more than 120 Coffea species. The most popular species is Coffea arabica (commonly known simply as "Arabica"). Coffeeberry^® is made from Arabica coffee plants grown on sustainable farms. The fruits are handpicked when they are ripe. The caffeine we get in a morning coffee, a cup of tea, or an energy drink can help us perform better physically and mentally.* It does this by promoting arousal (wakefulness), which is a necessary ingredient for being able to pay attention and react quickly. Not surprisingly, this has led to caffeine being one of the most widely used and studied substances for both sports performance and brain function. While caffeine gets most of the attention, coffee polyphenols support healthy function. Most nootropics use pure caffeine; a better approach is using a coffee extract that gives caffeine and the naturally occurring coffee fruit polyphenols. 

NEUROHACKER’S COFFEEBERRY^® SOURCING

Coffeeberry^® organic whole coffee fruit extract is produced by Futureceuticals, a leader in fruit and vegetable extracts. 

Futureceuticals calls this ingredient CoffeeBerry^® Energy, because it contains a minimum of 70% caffeine, along with polyphenols from coffee cherries. 

Made from carefully selected, hand-picked, premium Arabica coffee cherries. 

Sustainably sourced from farms certified Fairtrade International & Rainforest Alliance.

Coffeeberry^® is Rainforest Alliance Certified™, Non-GMO Project Verified, gluten-free, vegan, Kosher, organic, GRAS and eco-friendly. 

COFFEEBERRY^® FORMULATING PRINCIPLES AND RATIONALE

Because of its content of caffeine, we consider Coffeeberry^® Energy to follow hormetic dosing principles (see Neurohacker Dosing Principles) and to have a hormetic range (i.e., a dosing range below and above which results would be poorer). Caffeine is one of the most used, and best studied nootropic and ergogenic compounds. When used as a nootropic (i.e., to promote alertness, focus, reaction time, etc.) caffeine is typically dosed from 50 to 200 mg. When used as an ergogenic (i.e., for sports performance) just prior to exercise the upper end of the dose range can be as high as 600 mg [1]. In both of these cases, responses to caffeine tend to follow an adaptational (i.e., hormetic) curve, with low-to-moderate amounts of caffeine supporting better cognitive and sports performance, but servings above the higher end of the range hindering performance. We have selected a serving of Coffeeberry^® that delivers the amount of caffeine (~90 mg) found in a small cup of coffee. This is in the middle of the range for nootropic purposes and on the lower end of what’s used for ergogenic purposes.*

CAFFEINE KEY MECHANISMS

Supports brain function*

Adenosine receptor antagonist* [2]

Influences, via adenosine receptor antagonism, the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine and norepinephrine* [3,4]

Supports acetylcholine signaling* [4–7]

Supports dopamine signaling* [4,8–13]

Supports serotonin signaling* [4,7,14–17]

Supports glutamate signaling* [4,8,9]

Supports GABA signaling* [4,7]

Supports noradrenaline signaling* [4,16]

Supports cortical activation in the brain* [2,4]

Supports cerebral metabolism* [2,4]

Promotes wakefulness* [18]

Supports cognitive function*

Supports cognitive performance* [1,4,19–22]

Supports executive function* [23–25]

Supports information processing rate* [2,26,27]

Supports simple and sustained attention* [1,23,27,28]

Supports vigilance* [1,28]

Supports reaction time* [1,21,22,27]

Supports reasoning* [20]

Supports creative thinking* [24]

Supports resistance to mental fatigue* [26,28]

Supports neuroprotective functions* [29,30]

Supports a healthy mood*

Supports a positive mood* [4,21,22,25,31]

Promotes physical performance*

Supports resistance to physical fatigue* [19,22,23,32]

Supports resistance to perceived exhaustion* [1]

Supports muscle endurance and strength exercise activities* [1]

Promotes speed, power, and agility during intense exercise* [1] 

Other actions*

Supports metabolic rate* [33–35]

Non-selective phosphodiesterase inhibitor* [36]

Complementary ingredients*

Theobromine as a CNS stimulant, with faster onset and shorter duration than Theobromine* [37]

L-Theanine in cognitive performance* [26,38–40]

Choline donors (e.g., citicoline, alpha-GPC) to support attention, concentration, and working memory* [41]

L-ornithine to support mood and cognitive performance* [42]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

[1] T.M. McLellan, J.A. Caldwell, H.R. Lieberman, Neurosci. Biobehav. Rev. 71 (2016) 294–312.
[2] G. Burnstock, Advances in Experimental Medicine and Biology 986 (2013) 1–12.
[3] B.B. Fredholm, Pharmacol. Toxicol. 76 (1995) 93–101.
[4] B.B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, E.E. Zvartau, Pharmacol. Rev. 51 (1999) 83–133.
[5] E. Acquas, G. Tanda, G. Di Chiara, Neuropsychopharmacology 27 (2002) 182–193.
[6] A.J. Carter, W.T. O’Connor, M.J. Carter, U. Ungerstedt, J. Pharmacol. Exp. Ther. 273 (1995) 637–642.
[7] D. Shi, O. Nikodijević, K.A. Jacobson, J.W. Daly, Cell. Mol. Neurobiol. 13 (1993) 247–261.
[8] G. Racchetti, A. Lorusso, C. Schulte, D. Gavello, V. Carabelli, R. D’Alessandro, J. Meldolesi, J. Cell Sci. 123 (2010) 165–170.
[9] D. Quarta, J. Borycz, M. Solinas, K. Patkar, J. Hockemeyer, F. Ciruela, C. Lluis, R. Franco, A.S. Woods, S.R. Goldberg, S. Ferré, J. Neurochem. 91 (2004) 873–880.
[10] B.E. Garrett, S.G. Holtzman, Eur. J. Pharmacol. 262 (1994) 65–75.
[11] K.R. Powell, P.M. Iuvone, S.G. Holtzman, Pharmacol. Biochem. Behav. 69 (2001) 59–70.
[12] M. Solinas, S. Ferré, Z.-B. You, M. Karcz-Kubicha, P. Popoli, S.R. Goldberg, J. Neurosci. 22 (2002) 6321–6324.
[13] X. Zheng, S. Takatsu, H. Wang, H. Hasegawa, Pharmacol. Biochem. Behav. 122 (2014) 136–143.
[14] D.J. Haleem, A. Yasmeen, M.A. Haleem, A. Zafar, Life Sci. 57 (1995) PL285–92.
[15] S. Khaliq, S. Haider, F. Naqvi, T. Perveen, S. Saleem, D.J. Haleem, Pak. J. Pharm. Sci. 25 (2012) 21–25.
[16] M.D. Chen, W.H. Lin, Y.M. Song, P.Y. Lin, L.T. Ho, Zhonghua Yi Xue Za Zhi 53 (1994) 257–261.
[17] M. Okada, Y. Kawata, K. Kiryu, K. Mizuno, K. Wada, H. Tasaki, S. Kaneko, J. Neurochem. 69 (2002) 2581–2588.
[18] T. Porkka-Heiskanen, Handb. Exp. Pharmacol. (2011) 331–348.
[19] V. Maridakis, P.J. O’Connor, P.D. Tomporowski, Int. J. Neurosci. 119 (2009) 1239–1258.
[20] M.J. Jarvis, Psychopharmacology 110 (1993) 45–52.
[21] A. Nehlig, J. Alzheimers. Dis. 20 Suppl 1 (2010) S85–94.
[22] C.H.S. Ruxton, Nutr. Bull. 33 (2008) 15–25.
[23] J. Lanini, J.C.F. Galduróz, S. Pompéia, Hum. Psychopharmacol. 31 (2016) 29–43.
[24] K. Soar, E. Chapman, N. Lavan, A.S. Jansari, J.J.D. Turner, Appetite 105 (2016) 156–163.
[25] F.L. Dodd, D.O. Kennedy, L.M. Riby, C.F. Haskell-Ramsay, Psychopharmacology 232 (2015) 2563–2576.
[26] C.F. Haskell, D.O. Kennedy, A.L. Milne, K.A. Wesnes, A.B. Scholey, Biol. Psychol. 77 (2008) 113–122.
[27] S.J.L. Einöther, T. Giesbrecht, Psychopharmacology 225 (2013) 251–274.
[28] A. Smith, Food Chem. Toxicol. 40 (2002) 1243–1255.
[29] M.A. Schwarzschild, K. Xu, E. Oztas, J.P. Petzer, K. Castagnoli, N. Castagnoli Jr, J.-F. Chen, Neurology 61 (2003) S55–61.
[30] M. Kolahdouzan, M.J. Hamadeh, CNS Neurosci. Ther. 23 (2017) 272–290.
[31] S.H. Backhouse, S.J.H. Biddle, N.C. Bishop, C. Williams, Appetite 57 (2011) 247–252.
[32] J.M. Davis, Z. Zhao, H.S. Stock, K.A. Mehl, J. Buggy, G.A. Hand, Am. J. Physiol. Regul. Integr. Comp. Physiol. 284 (2003) R399–404.
[33] K.J. Acheson, B. Zahorska-Markiewicz, P. Pittet, K. Anantharaman, E. Jéquier, Am. J. Clin. Nutr. 33 (1980) 989–997.
[34] A. Astrup, S. Toubro, S. Cannon, P. Hein, L. Breum, J. Madsen, Am. J. Clin. Nutr. 51 (1990) 759–767.
[35] J. LeBlanc, M. Jobin, J. Côté, P. Samson, A. Labrie, J. Appl. Physiol. 59 (1985) 832–837.
[36] O.H. Choi, M.T. Shamim, W.L. Padgett, J.W. Daly, Life Sci. 43 (1988) 387–398.
[37] R. Franco, A. Oñatibia-Astibia, E. Martínez-Pinilla, Nutrients 5 (2013) 4159–4173.
[38] S.J.L. Einöther, V.E.G. Martens, J.A. Rycroft, E.A. De Bruin, Appetite 54 (2010) 406–409.
[39] T. Giesbrecht, J.A. Rycroft, M.J. Rowson, E.A. De Bruin, Nutr. Neurosci. 13 (2010) 283–290.
[40] G.N. Owen, H. Parnell, E.A. De Bruin, J.A. Rycroft, Nutr. Neurosci. 11 (2008) 193–198.
[41] S.E. Bruce, K.B. Werner, B.F. Preston, L.M. Baker, Int. J. Food Sci. Nutr. 65 (2014) 1003–1007.
[42] A. Misaizu, T. Kokubo, K. Tazumi, M. Kanayama, Y. Miura, Prev Nutr Food Sci 19 (2014) 367–372.

Ginkgo Biloba Leaf Extract (24% glycosides)

Scientific Name:
Ginkgo biloba

Bacopa monnieri Extract

Scientific Name:
Bacopa monnieri

Mucuna Pruriens Extract

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

Huperzia serrata Leaf extract (1% Huperzine A)

Scientific Name:
Huperzine A extracted  from Huperzia serrata

Inositol-enhanced Bonded Arginine Silicate (as nooLVL™)

COMMON NAME

Inositol-enhanced Bonded Arginine Silicate

TOP BENEFITS OF NooLVL^TM

Enhances processing speed and accuracy*

Supports executive function*

Boosts energy*

Promotes muscle performance*

WHAT IS NooLVL^TM?

NooLVL^TM is comprised of two components: Bonded (inositol-stabilized) arginine silicate (Nitrosigine^®) plus additional inositol. L-arginine has relatively low bioavailability (~20%) following an oral dose, so high doses are needed to significantly boost blood arginine levels [1]. Nitrosigine^® and NooLVL^TM have overcome this limitation by bonding the L-arginine to a silicate–inositol complex, which significantly enhances the bioavailability of L-arginine [2–5]. L-arginine is involved in promoting healthy circulation because it can be used for nitric oxide production. Blood flow to metabolically active tissues, like the brain and muscles, plays a big role in allowing these tissues to perform their functions at a high level. Bonded arginine silicate supports exercise performance and post-exercise recovery by promoting muscle blood flow [6]. It also supports brain performance, enhancing mental accuracy, focus, processing speed, and executive function [5,7,8].

NEUROHACKER’S NooLVL^TM SOURCING

NooLVL^TM has been clinically studied in humans: It has boosted cognitive performance and energy in eSports athletes.

NooLVL^TM is an upgraded version of Nitrosigine^®, an ingredient that supports blood arginine levels and nitric oxide production, enhanced energy, promoted focus and mental acuity, and supported better muscle response following exercise. 

NooLVL^TM is a patented nutritional ingredient from Nutrition 21: It contains Nitrosigine^® (l-arginine bonded to silica and inositol with affirmed GRAS) plus added inositol. 

NooLVL^TM is gluten-free, vegan, and non-GMO.

NooLVL^TM is a trademark of Nutrition 21, LLC.

NooLVL^TM FORMULATING PRINCIPLES AND RATIONALE

The studied serving of NooLVLTM has been 1600 mg/day: Nitrosigine® has been 1500 mg/day. Since these are the highest amounts that have been given in human research, we consider them to be the upper limit we’d be comfortable with for daily serving. Since it’s possible that the product this is included in might be used more than once a day (i.e., a person could opt to take two servings), we included half that amount per serving (i.e., 800 mg of NooLVLTM). In Neurohacker’s subjective and objective internal N of 1 testing, the half serving of NooLVLTM had additive effects when combined with other nootropic ingredients.*

NooLVL^TM KEY MECHANISMS

Supports healthy vascular function*

L-arginine is the substrate for vascular nitric oxide (NO) production by NO synthase (NOS) [9]

Upregulates endothelial NOS (eNOS) [silicate] [10]

Upregulates the blood levels of arginine, silicon, and NO [4]

Supports healthy vascular function [2]

Supports healthy blood pressure [arginine] [11] [inositol] [12,13]

Supports brain function*

Upregulates dopamine release [14–16].

Regulates dopamine transporter (DAT) activity [17–20]. 

Supports neurotransmitter signaling [inositol] [21]

Supports cognitive function*

Supports performance in complex cognitive tests requiring mental flexibility, processing speed and executive functioning [7]

Promotes exercise performance*

Supports exercise performance [arginine] [22]

Supports resistance to exhaustion [arginine] [22]

Supports resistance to muscle fatigue [arginine] [23]

Supports muscle blood flow after exercise [6]

Supports muscle recovery [6]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

[1]O. Tangphao, M. Grossmann, S. Chalon, B.B. Hoffman, T.F. Blaschke, Br. J. Clin. Pharmacol. 47 (1999) 261–266.

[2]S.D. Proctor, S.E. Kelly, J.C. Russell, Diabetologia 48 (2005) 1925–1932.

[3]S.D. Proctor, S.E. Kelly, D.F. Vine, J.C. Russell, Metabolism 56 (2007) 1318–1325.

[4]D.S. Kalman, S. Feldman, A. Samson, D.R. Krieger, Clin. Pharmacol. 7 (2015) 103–109.

[5]J. Komorowski, S.P. Ojalvo, The FASEB Journal 30 (2016) 690.17–690.17.

[6]S. Rood-Ojalvo, D. Sandler, E. Veledar, J. Komorowski, J. Int. Soc. Sports Nutr. 12 (2015) P14.

[7]D. Kalman, P.D. Harvey, S. Perez Ojalvo, J. Komorowski, Nutrients 8 (2016).

[8]S. Sylla, S.P. Ojalvo, J. Komorowski, The FASEB Journal 32 (2018) 724.12–724.12.

[9]N.W. Rajapakse, D.L. Mattson, Clin. Exp. Pharmacol. Physiol. 36 (2009) 249–255.

[10]B. Buffoli, E. Foglio, E. Borsani, C. Exley, R. Rezzani, L.F. Rodella, Acta Histochem. 115 (2013) 418–424.

[11]J.-Y. Dong, L.-Q. Qin, Z. Zhang, Y. Zhao, J. Wang, F. Arigoni, W. Zhang, Am. Heart J. 162 (2011) 959–965.

[12]A. Santamaria, D. Giordano, F. Corrado, B. Pintaudi, M.L. Interdonato, G.D. Vieste, A.D. Benedetto, R. D’Anna, Climacteric 15 (2012) 490–495.

[13]D. Giordano, F. Corrado, A. Santamaria, S. Quattrone, B. Pintaudi, A. Di Benedetto, R. D’Anna, Menopause 18 (2011) 102–104.

[14]L.P. Liang, S. Kaufman, Brain Res. 800 (1998) 181–186.

[15]M.T. Silva, S. Rose, J.G. Hindmarsh, P. Jenner, C.D. Marsden, Neuroreport 9 (1998) 149–152.

[16]A. Strasser, R.M. McCarron, H. Ishii, D. Stanimirovic, M. Spatz, Neuroreport 5 (1994) 2298–2300.

[17]T.J. Volz, J.O. Schenk, Synapse 54 (2004) 173–182.

[18]J.P. Kiss, G. Zsilla, E.S. Vizi, Neurochem. Int. 45 (2004) 485–489.

[19]J.P. Kiss, E.C. Hennings, G. Zsilla, E.S. Vizi, Neurochem. Int. 34 (1999) 345–350.

[20]V. Chaparro-Huerta, C. Beas-Zárate, M.U. Guerrero, A. Feria-Velasco, Neurochem. Int. 31 (1997) 607–616.

[21]S.K. Fisher, J.E. Novak, B.W. Agranoff, J. Neurochem. 82 (2002) 736–754.

[22]H.U. Yavuz, H. Turnagol, A.H. Demirel, Biol. Sport 31 (2014) 187–191.

[23]A. Schaefer, F. Piquard, B. Geny, S. Doutreleau, E. Lampert, B. Mettauer, J. Lonsdorfer, Int. J. Sports Med. 23 (2002) 403–407.

Saffron Stigma Extract

Scientific Name:
Crocus sativus

COMMON NAME

Saffron | Saffron Crocus

TOP BENEFITS OF SAFFRON

Supports mood*

Supports cognitive function*

Supports vision*

WHAT IS SAFFRON?

Saffron is a spice derived from the flowers of Crocus sativus. It’s been used and traded as a spice for at least 4000 years and is considered the world's most costly spice by weight. Saffron has had a wide range and long list of traditional uses. In Traditional Iranian Medicine saffron was thought to be useful for supporting sleep and mood, and to be a heart tonic. And in India it was used as a nerve and heart tonic, and for relaxation and sleep support. Iran produces the majority of saffron: Greece, Kashmir, Morocco, Spain and Turkey are also fairly large growers. Saffron, as a spice, refers to the deep red-maroon colored stigma and styles (called threads). Not all saffron is of the same quality and strength, with price increasing substantially for the highest grades. In general, the content of several of saffron’s active compounds are used to determine strength. A greater content of crocin (responsible for saffron's color), picrocrocin (a bitter compound giving the characteristic taste), and safranal (which gives the fragrance) would be graded as higher strength. In addition to these marker compounds, saffron also contains zeaxanthin, lycopene, and other carotenoids. Crocin also belongs to the carotenoid family. Most carotenoids only dissolve in oil (i.e., are fat-soluble). Crocin is water-soluble, which is part of the reason it is used in rice dishes and other water-based food recipes. There’s been a growing interest in the use of saffron for health purposes, including in areas such as mood, cognition, vision, sports performance, appetite regulation, metabolic function, sleep, and women’s health.*

NEUROHACKER’S SAFFRON SOURCING

There's a long history of saffron adulteration. Because of this, Neurohacker feels it is critical to use a standardized saffron extract purchased from an ingredient supplier that can authenticate quality and strength.

The saffron extract we use is sourced from Spain, has been authenticated, and is standardized for 0.3% safranal.

Saffron extract used in our products is GRAS, non-GMO, gluten-free, vegan, Kosher certified and Halal compliant. 

SAFFRON FORMULATING PRINCIPLES AND RATIONALE

Some saffron studies in humans have used highly standardized extracts, with servings typically in the range of 20-30 mg per day. Many other studies have used saffron powder (unstandardized) with servings often ranging from 50-300 mg daily. We source an extract that is between these two extremes—standardized, but not as highly standardized, because we believe capturing more of the essence of whole saffron stigmas is the most suitable approach for promoting health with this ingredient. Since studies comparing multiple amounts or different standardizations have not been published, there’s no information on whether saffron has a threshold effect (i.e., an amount or range less than the full serving where the majority of the response would occur; see Neurohacker Dosing Principles) or how different extract strengths compare to each other or to saffron powder. However, individual (i.e. N of 1) subjective response to saffron does vary considerably, with some persons reporting noticeable differences when taking as little as 1-3 mg of a standardized saffron extract. Depending on the purpose Neurohacker is using saffron for, and the other ingredients it’s combined with, the recommended serving may be anywhere ranging from a more micro-serving level up (3 mg) up to a serving of 20 mg per day.*

SAFFRON KEY MECHANISMS

Supports a healthy mood*

Supports a positive mental-emotional bias [1–9]

Supports a calm mood [3,4,7–9]

Supports brain function*

Supports focus and attention [10]

Supports healthy brain aging [11–13]

Supports sleep [14–16]

Supports dopamine signaling [17,18]

Supports GABA-glutamate signaling [17]

Supports acetylcholinesterase activity [18]

Supports brain-derived neurotrophic factor (BDNF) levels [19,20]

Supports neuroprotective functions [18,21–25]

Supports long-term potentiation [15]

Supports vision*

Supports healthy retinal function [22,26–33]

Supports macular health [27,30,33]

Supports visual acuity [30,33]

Supports protection of retinal cells from light-induced damage [28,34–36]

Supports healthy intraocular pressure [37]

Promotes exercise performance*

Supports reaction times [38]

Supports muscle strength [38]

Supports muscle recovery functions [39]

Supports antioxidant defenses*

Supports antioxidant enzymes [18,21,32]

Supports the replenishment of glutathione (GSH) levels [18,32]

Supports free-radical scavenging [18,21,31,32]

Supports healthy prooxidant-antioxidant balance [40]

Supports mitochondrial function*

Supports the activity of mitochondrial enzymes [18]

Supports mitochondrial membrane potential [31]

Supports healthy metabolic function*

Supports cytokine balance [41]

Supports appetite regulation [42]

Supports healthy lipid levels and blood pressure regulation [43,44] 

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

[1]H.A. Hausenblas, D. Saha, P.J. Dubyak, S.D. Anton, J. Integr. Med. 11 (2013) 377–383.

[2]A.L. Lopresti, P.D. Drummond, Hum. Psychopharmacol. 29 (2014) 517–527.

[3]G. Kell, A. Rao, G. Beccaria, P. Clayton, A.M. Inarejos-García, M. Prodanov, Complement. Ther. Med. 33 (2017) 58–64.

[4]A.L. Lopresti, P.D. Drummond, A.M. Inarejos-García, M. Prodanov, J. Affect. Disord. 232 (2018) 349–357.

[5]S. Akhondzadeh, N. Tahmacebi-Pour, A.-A. Noorbala, H. Amini, H. Fallah-Pour, A.-H. Jamshidi, M. Khani, Phytother. Res. 19 (2005) 148–151.

[6]E. Moshiri, A.A. Basti, A.-A. Noorbala, A.-H. Jamshidi, S. Hesameddin Abbasi, S. Akhondzadeh, Phytomedicine 13 (2006) 607–611.

[7]A. Ghajar, S.M. Neishabouri, N. Velayati, L. Jahangard, N. Matinnia, M. Haghighi, A. Ghaleiha, M. Afarideh, S. Salimi, A. Meysamie, S. Akhondzadeh, Pharmacopsychiatry 50 (2017) 152–160.

[8]M. Mazidi, M. Shemshian, S.H. Mousavi, A. Norouzy, T. Kermani, T. Moghiman, A. Sadeghi, N. Mokhber, M. Ghayour-Mobarhan, G.A.A. Ferns, J. Complement. Integr. Med. 13 (2016) 195–199.

[9]A. Milajerdi, S. Jazayeri, E. Shirzadi, N. Hashemzadeh, A. Azizgol, A. Djazayery, A. Esmaillzadeh, S. Akhondzadeh, Complement. Ther. Med. 41 (2018) 196–202.

[10]S. Baziar, A. Aqamolaei, E. Khadem, S.H. Mortazavi, S. Naderi, E. Sahebolzamani, A. Mortezaei, S. Jalilevand, M.-R. Mohammadi, M. Shahmirzadi, S. Akhondzadeh, J. Child Adolesc. Psychopharmacol. 29 (2019) 205–212.

[11]M. Farokhnia, M. Shafiee Sabet, N. Iranpour, A. Gougol, H. Yekehtaz, R. Alimardani, F. Farsad, M. Kamalipour, S. Akhondzadeh, Hum. Psychopharmacol. 29 (2014) 351–359.

[12]S. Akhondzadeh, M.S. Sabet, M.H. Harirchian, M. Togha, H. Cheraghmakani, S. Razeghi, S.S. Hejazi, M.H. Yousefi, R. Alimardani, A. Jamshidi, F. Zare, A. Moradi, J. Clin. Pharm. Ther. 35 (2010) 581–588.

[13]S. Akhondzadeh, M. Shafiee Sabet, M.H. Harirchian, M. Togha, H. Cheraghmakani, S. Razeghi, S.S. Hejazi, M.H. Yousefi, R. Alimardani, A. Jamshidi, S.-A. Rezazadeh, A. Yousefi, F. Zare, A. Moradi, A. Vossoughi, Psychopharmacology 207 (2010) 637–643.

[14]M. Masaki, K. Aritake, H. Tanaka, Y. Shoyama, Z.-L. Huang, Y. Urade, Mol. Nutr. Food Res. 56 (2012) 304–308.

[15]S. Soeda, K. Aritake, Y. Urade, H. Sato, Y. Shoyama, Adv Neurobiol 12 (2016) 275–292.

[16]Z. Liu, X.-H. Xu, T.-Y. Liu, Z.-Y. Hong, Y. Urade, Z.-L. Huang, W.-M. Qu, CNS Neurosci. Ther. 18 (2012) 623–630.

[17]H. Ettehadi, S.N. Mojabi, M. Ranjbaran, J. Shams, H. Sahraei, M. Hedayati, F. Asefi, JBBS 03 (2013) 315–319.

[18]S.V. Rao, Muralidhara, S.C. Yenisetti, P.S. Rajini, Neurotoxicology 52 (2016) 230–242.

[19]T. Ghasemi, K. Abnous, F. Vahdati, S. Mehri, B.M. Razavi, H. Hosseinzadeh, Drug Res. 65 (2015) 337–343.

[20]F. Vahdati Hassani, V. Naseri, B.M. Razavi, S. Mehri, K. Abnous, H. Hosseinzadeh, Daru 22 (2014) 16.

[21]B. Naghizadeh, M.T. Mansouri, B. Ghorbanzadeh, Y. Farbood, A. Sarkaki, Phytomedicine 20 (2013) 537–542.

[22]S. Purushothuman, C. Nandasena, C.L. Peoples, N. El Massri, D.M. Johnstone, J. Mitrofanis, J. Stone, J. Parkinsons. Dis. 3 (2013) 77–83.

[23]Y.S. Batarseh, S.S. Bharate, V. Kumar, A. Kumar, R.A. Vishwakarma, S.B. Bharate, A. Kaddoumi, ACS Chem. Neurosci. 8 (2017) 1756–1766.

[24]L. Tamegart, A. Abbaoui, R. Makbal, M. Zroudi, B. Bouizgarne, M.M. Bouyatas, H. Gamrani, Acta Histochem. 121 (2019) 171–181.

[25]P. Haeri, A. Mohammadipour, Z. Heidari, A. Ebrahimzadeh-Bideskan, Anat. Sci. Int. 94 (2019) 119–127.

[26]A. Lashay, G. Sadough, E. Ashrafi, M. Lashay, M. Movassat, S. Akhondzadeh, Med Hypothesis Discov Innov Ophthalmol 5 (2016) 32–38.

[27]M. Piccardi, D. Marangoni, A.M. Minnella, M.C. Savastano, P. Valentini, L. Ambrosio, E. Capoluongo, R. Maccarone, S. Bisti, B. Falsini, Evid. Based. Complement. Alternat. Med. 2012 (2012) 429124.

[28]B. Falsini, M. Piccardi, A. Minnella, C. Savastano, E. Capoluongo, A. Fadda, E. Balestrazzi, R. Maccarone, S. Bisti, Invest. Ophthalmol. Vis. Sci. 51 (2010) 6118–6124.

[29]G.K. Broadhead, J.R. Grigg, P. McCluskey, T. Hong, T.E. Schlub, A.A. Chang, Graefes Arch. Clin. Exp. Ophthalmol. 257 (2019) 31–40.

[30]R. Maccarone, S. Di Marco, S. Bisti, Invest. Ophthalmol. Vis. Sci. 49 (2008) 1254–1261.

[31]F.D. Marco, S. Romeo, C. Nandasena, S. Purushothuman, C. Adams, S. Bisti, J. Stone, Am. J. Neurodegener. Dis. 2 (2013) 208–220.

[32]A. Laabich, G.P. Vissvesvaran, K.L. Lieu, K. Murata, T.E. McGinn, C.C. Manmoto, J.R. Sinclair, I. Karliga, D.W. Leung, A. Fawzi, R. Kubota, Invest. Ophthalmol. Vis. Sci. 47 (2006) 3156–3163.

[33]M. Yamauchi, K. Tsuruma, S. Imai, T. Nakanishi, N. Umigai, M. Shimazawa, H. Hara, Eur. J. Pharmacol. 650 (2011) 110–119.

[34]R. Natoli, Y. Zhu, K. Valter, S. Bisti, J. Eells, J. Stone, Mol. Vis. 16 (2010) 1801–1822.

[35]B. Lv, T. Chen, Z. Xu, F. Huo, Y. Wei, X. Yang, Int. J. Mol. Med. 37 (2016) 225–232.

[36]L. Chen, Y. Qi, X. Yang, Ophthalmic Res. 54 (2015) 157–168.

[37]M.H. Jabbarpoor Bonyadi, S. Yazdani, S. Saadat, BMC Complement. Altern. Med. 14 (2014) 399.

[38]A. Meamarbashi, A. Rajabi, J. Diet. Suppl. 13 (2016) 522–529.

[39]A. Meamarbashi, A. Rajabi, Clin. J. Sport Med. 25 (2015) 105–112.

[40]T. Kermani, S.H. Mousavi, M. Shemshian, A. Norouzy, M. Mazidi, A. Moezzi, T. Moghiman, M. Ghayour-Mobarhan, G. A Ferns, Avicenna J Phytomed 5 (2015) 427–433.

[41]T. Kermani, M. Zebarjadi, H. Mehrad-Majd, S.-R. Mirhafez, M. Shemshian, F. Ghasemi, E. Mohammadzadeh, S.H. Mousavi, A. Norouzy, T. Moghiman, A. Sadeghi, G. Ferns, A. Avan, E. Mahdipour, M. Ghayour-Mobarhan, Curr. Clin. Pharmacol. 12 (2017) 122–126.

[42]N. Abedimanesh, S.Z. Bathaie, S. Abedimanesh, B. Motlagh, A. Separham, A. Ostadrahimi, J Cardiovasc Thorac Res 9 (2017) 200–208.

[43]F. Ebrahimi, N. Aryaeian, N. Pahlavani, D. Abbasi, A.F. Hosseini, S. Fallah, N. Moradi, I. Heydari, Avicenna J Phytomed 9 (2019) 322–333.

[44]A. Moravej Aleali, R. Amani, H. Shahbazian, F. Namjooyan, S.M. Latifi, B. Cheraghian, Phytother. Res. 33 (2019) 1648–1657.