Apigenin (from Citrus grandis Fruit Extract)

Common Name

Apigenin


Top Benefits of Apigenin

Supports mitochondrial function and cellular energy *

Supports exercise performance *

Supports metabolism *

Supports healthy weight *

Supports antioxidant defenses *

Supports healthy cellular responses *

Supports cardiovascular function *

Supports brain function *

Supports kidney health *

Supports healthy gut microbiota * 


What is Apigenin?

Apigenin belongs to the flavone class of flavonoids. It is one of the more common flavones in the diet, found in many fruits and vegetables, including celery and parsley. It is found in very high amounts in the flowers used to make chamomile tea. Apigenin has been reported to support cardiovascular, brain, and kidney function, and metabolic benefits. It indirectly boosts NAD+ by modulating the activity of the CD38 NAD+-consuming pathway. Apigenin is also supportive of antioxidant defenses and the mitochondrial cellular energy network.*


Neurohacker’s Apigenin Sourcing

Citrus grandis (i.e., pomelo) fruit extract was selected as an ingredient to provide a standardized amount of apigenin. Pomelo is one of the original ancestral citrus fruits from which all modern cultivated citrus varieties originated. They are consumed as a fruit throughout Southeast Asia. A pomelo is somewhat similar in appearance to a large grapefruit. This is because grapefruits originated as a back-cross of pomelo and sweet orange. Peels of pomelo (or grapefruits) are often used to produce the apigenin found in dietary supplements.


Apigenin Dosing Principles and Rationale

Flavonoid molecules are part of plants’ protective responses to mild environmental stress. Consuming them tends to produce adaptive functional responses, upregulating pathways that provide stress resistance. Because of this, we don’t think of flavones like apigenin as being “more is better” ingredients. Instead, we think it’s better to use them following hormetic dosing principles (see Neurohacker Dosing Principles). Because of this, we use a low dose of apigenin. Flavonoids are additive, and often complementary with other polyphenol compounds, so the combination of all polyphenols in a formulation should be considered when determining dosage (not the amount of a single polyphenol molecule in isolation).*


Apigenin Key Mechanisms 


Supports mitochondrial biogenesis*

Supports peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling [1]

Supports nuclear transcription factors of mitochondrial biogenesis (TFAM) [1]

Supports mitochondrial size/density/number [1]


Supports mitochondrial function*

Supports mitochondrial function [1,2]

Supports electron transport chain and oxidative phosphorylation proteins/genes (supports ATP production) [1,3]

Supports complex I-V activity [2,4]

Supports NAD+ generation [5]

Supports citric acid cycle proteins/genes [3]


Supports signaling pathways*

Supports AMP-activated protein kinase (AMPK) [1,6–11]

Supports peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) [12,13]

Supports liver kinase B1 (LKB1) [9]


Promotes exercise performance*

Supports endurance performance [1] 

Supports muscle structure/function [1]


Supports healthy metabolic function*

Supports healthy blood glucose levels [1,3,5,12,14]

Supports healthy insulin sensitivity [1,3]

Supports fatty acid metabolism proteins/genes [3]

Supports β-oxidation (fatty acid metabolism) [5]


Supports healthy body weight*

Downregulates fat accumulation and blood/liver lipid levels [1,3,6,13,14]

Downregulates adipocyte differentiation and lipid accumulation [7]

Downregulates adipogenesis - downregulates peroxisome proliferator-activated receptor gamma (PPARγ) [3]

Supports lean mass [1] 


Supports antioxidant defenses*

Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [12–18]

Downregulates the generation of reactive oxygen species [2,8,15]

Replenishes glutathione (GSH) levels [12,13,15,17]


Supports healthy cardiovascular function*

Supports ECG parameters, hemodynamics, and left ventricular function [12]

Protects from cardiac injury and dysfunction [4,12,19]

Protects from vascular damage [2,14]

Supports healthy vascular function [6,8]

Supports healthy blood pressure  [8]

Supports healthy cholesterol levels [6,14]


Supports brain function*

Neuroprotective effects [15,16]

Protects cognitive function [17]

Downregulates amyloid-beta accumulation [17] 


Supports a healthy gut microbiota*

Regulates the composition of the gut microbiota [20,21]

Modulates gut microbial gene expression [21]


Promotes healthy aging and longevity*

Supports SIRT-1 signaling [8]

Influences mTOR signaling [9,11,19,22–24]

Supports insulin-like growth factor-1 (IGF-1) signaling [25,26]

Supports healthy immune signaling [1,3,13,16,22]

Influences NF-κB signaling [4,13,14,22]

 

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


REFERENCES

[1]W.H. Choi, H.J. Son, Y.J. Jang, J. Ahn, C.H. Jung, T.Y. Ha, Mol. Nutr. Food Res. 61 (2017).

[2]S. Duarte, D. Arango, A. Parihar, P. Hamel, R. Yasmeen, A.I. Doseff, Int. J. Mol. Sci. 14 (2013) 17664–17679.

[3]U.J. Jung, Y.-Y. Cho, M.-S. Choi, Nutrients 8 (2016).

[4]H. Cardenas, D. Arango, C. Nicholas, S. Duarte, G.J. Nuovo, W. He, O.H. Voss, M.E. Gonzalez-Mejia, D.C. Guttridge, E. Grotewold, A.I. Doseff, Int. J. Mol. Sci. 17 (2016) 323.

[5]C. Escande, V. Nin, N.L. Price, V. Capellini, A.P. Gomes, M.T. Barbosa, L. O’Neil, T.A. White, D.A. Sinclair, E.N. Chini, Diabetes 62 (2013) 1084–1093.

[6]T.Y. Wong, Y.Q. Tan, S.-M. Lin, L.K. Leung, Biomed. Pharmacother. 96 (2017) 1000–1007.

[7]M. Ono, K. Fujimori, J. Agric. Food Chem. 59 (2011) 13346–13352.

[8]X. Wei, P. Gao, Y. Pu, Q. Li, T. Yang, H. Zhang, S. Xiong, Y. Cui, L. Li, X. Ma, D. Liu, Z. Zhu, Clin. Sci. 131 (2017) 567–581.

[9]X. Tong, K.A. Smith, J.C. Pelling, Mol. Carcinog. 51 (2012) 268–279.

[10]M. Zang, S. Xu, K.A. Maitland-Toolan, A. Zuccollo, X. Hou, B. Jiang, M. Wierzbicki, T.J. Verbeuren, R.A. Cohen, Diabetes 55 (2006) 2180–2191.

[11]B.B. Bridgeman, P. Wang, B. Ye, J.C. Pelling, O.V. Volpert, X. Tong, Cell. Signal. 28 (2016) 460–468.

[12]U.B. Mahajan, G. Chandrayan, C.R. Patil, D.S. Arya, K. Suchal, Y.O. Agrawal, S. Ojha, S.N. Goyal, Int. J. Mol. Sci. 18 (2017).

[13]F. Wang, J.-C. Liu, R.-J. Zhou, X. Zhao, M. Liu, H. Ye, M.-L. Xie, Chem. Biol. Interact. 275 (2017) 171–177.

[14]B. Ren, W. Qin, F. Wu, S. Wang, C. Pan, L. Wang, B. Zeng, S. Ma, J. Liang, Eur. J. Pharmacol. 773 (2016) 13–23.

[15]Y. Han, T. Zhang, J. Su, Y. Zhao, Chenchen, Wang, X. Li, J. Clin. Neurosci. 40 (2017) 157–162.

[16]F. Zhang, F. Li, G. Chen, Neurol. Sci. 35 (2014) 583–588.

[17]L. Zhao, J.-L. Wang, R. Liu, X.-X. Li, J.-F. Li, L. Zhang, Molecules 18 (2013) 9949–9965.

[18]S.E. Nielsen, J.F. Young, B. Daneshvar, S.T. Lauridsen, P. Knuthsen, B. Sandström, L.O. Dragsted, Br. J. Nutr. 81 (1999) 447–455.

[19]W. Yu, H. Sun, W. Zha, W. Cui, L. Xu, Q. Min, J. Wu, Evid. Based. Complement. Alternat. Med. 2017 (2017) 2590676.

[20]L. Li, S. Somerset, Nutrients 10 (2018).

[21]M. Wang, J. Firrman, L. Zhang, G. Arango-Argoty, P. Tomasula, L. Liu, W. Xiao, K. Yam, Molecules 22 (2017).

[22]A. Kim, C.S. Lee, Naunyn. Schmiedebergs. Arch. Pharmacol. 391 (2018) 271–283.

[23]T.A. Stump, B.N. Santee, L.P. Williams, R.A. Kunze, C.E. Heinze, E.D. Huseman, R.J. Gryka, D.S. Simpson, S. Amos, J. Pharm. Pharmacol. 69 (2017) 907–916.

[24]J. Yang, C. Pi, G. Wang, Biomed. Pharmacother. 103 (2018) 699–707.

[25]M.A. Babcook, S. Gupta, Curr. Drug Targets (2012).

[26]S. Shukla, G.T. MacLennan, P. Fu, S. Gupta, Pharm. Res. 29 (2012) 1506–1517.