Apigenin (from Citrus grandis Fruit Extract)

Top Benefits of Apigenin

Supports mitochondrial function and cellular energy *

Supports metabolic function *

Supports antioxidant defenses *

Supports healthy aging and longevity *

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 Formulating 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 serving 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 serving size (not the amount of a single polyphenol molecule in isolation).*

Apigenin Key Mechanisms 

Supports mitochondrial structure and function*

Supports transcription factors of mitochondrial biogenesis (PGC-1α, TFAM)* [1]

Supports mitochondrial size/density/number* [1]

Supports electron transport chain and ATP production* [1–4]

Supports NAD+ generation* [5]

Supports citric acid cycle function* [2]

Supports healthy metabolic function*

Supports healthy blood glucose levels* [1,2,5–7]

Supports β-oxidation (fatty acid metabolism)* [2,5]

Supports healthy blood/liver lipid levels* [1,2,7–9]

Downregulates adipocyte differentiation, adipogenesis, and lipid accumulation* [2,10]

Supports antioxidant defenses*

Supports antioxidant defenses* [6,7,9,11–14]

Counters ROS production* [3,11,15]

Replenishes glutathione (GSH) levels* [6,9,11,13]

Supports healthy aging and longevity*

Supports neuroprotective functions* [11–13] 

Supports healthy cardiovascular structure and function* [3,4,6–8,15,16]

Supports healthy gut microbiota composition* [17,18]

Supports AMPK signaling* [1,8,10,15,19–21]

Supports PPARα and PPARγ signaling* [6,9]

Supports SIRT-1 signaling* [15]

Influences mTOR signaling* [16,19,21–24]

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

Supports healthy immune signaling* [1,2,9,12,22]

Influences NF-κB signaling* [4,7,9,22]

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

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

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

[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]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).

[7]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.

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

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

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

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

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

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

[14]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.

[15]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.

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

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

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

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

[20]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.

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

[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.