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Apigenin

Apigenin is a flavonoid with a broad spectrum of biological activities, including effects on metabolism, inflammation, neuroprotection, and anti-cancer properties. It acts as a potent inhibitor of CD38, a key enzyme that reduces NAD levels, thereby influencing several cell signaling pathways.
Apigenin has also been shown to influence weight, inflammation, and insulin resistance by altering the gut microbiota and restoring the richness and diversity of the gut microbiota.

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Cellular Pathways

Inhibition of CD38 is the core pathway for mitigating age-related decline. CD38 is the main enzyme that degrades NAD+.

Why this matters:

CD38 is abundant in inflammatory cells and key in the decline of NAD+, crucial for cell functions. With aging, CD38 expression, mRNA, and NADase activity increase, accelerating cellular aging. Overexpression of CD38 in cancer cells triggers aging-like features. Also, low-grade inflammation during aging boosts CD38 expression in inflammatory cells, leading to their accumulation in tissues, indicating CD38’s significant role in the cycle of aging and inflammation.

Clinical Studies

CD38 Degrades NAD+ Precursors

Implications for NAD+ Replacement Therapy

  • CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of the SIRT3 activity.
  • NAD replacement-based therapies with NMN and NR for metabolic dysfunction could be significantly improved by combination with CD38 inhibitors.

Synergy with NAD

precursors, Guttides, Leusynergy
Apigenin™ + (NMN, NR, 5-amino, NAD injection)
Apigenin in conjunction with NAD precursors like NMN, NR, 5-amino1mq and NAD injections create a systematic approach to cellular efficiency.
Due to Apigenin effects on the microbiome and akkermensia, it is commonly added to gut health protocol using Guttides, Larazotide and butryrate.
Apigenin is also used in combination with peptides and supplements that improve metabolism such as GLP-1s and Sermorelin.

References

  1. Dongtao Wang, Yajun Yang, Xiaohu Zou, Jing Zhang, Zena Zheng, Ziwei Wang, Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice, The Journals of Gerontology: Series A, Volume 75, Issue 11, November 2020, Pages 2081–2088, https://doi.org/10.1093/gerona/glaa214
  2. Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+ -CD38 Axis. Bing Si Li (1Department of Biochemistry, Wonkwang University School of Medicine, 460 Iksandaero, Iksan, Jeonbuk 54538, Republic of Korea), Ri Zhe Zhu (1Department of Biochemistry, Wonkwang University School of Medicine, 460 Iksandaero, Iksan, Jeonbuk 54538, Republic of Korea), Seok-Hee Lim (1Department of Biochemistry, Wonkwang University School of Medicine, 460 Iksandaero, Iksan, Jeonbuk 54538, Republic of Korea), Jae Ho Seo (1Department of Biochemistry, Wonkwang University School of Medicine, 460 Iksandaero, Iksan, Jeonbuk 54538, Republic of Korea), and Byung-Min Choi (1Department of Biochemistry, Wonkwang University School of Medicine, 460 Iksandaero, Iksan, Jeonbuk 54538, Republic of Korea) The American Journal of Chinese Medicine 2021 49:05, 1235-1250
  3. Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O’Neil L, White TA, Sinclair DA, Chini EN. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013 Apr;62(4):1084-93. doi: 10.2337/db12-1139. Epub 2012 Nov 19. PMID: 23172919; PMCID: PMC3609577.
  4. Qiao Y, Zhang Z, Zhai Y, Yan X, Zhou W, Liu H, Guan L, Peng L. Apigenin Alleviates Obesity-Associated Metabolic

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These statements have not been evaluated by the Food and Drug Administration. The products and information on this website are not intended to diagnose, treat, cure or prevent any disease. The information on this site is for educational purposes only and should not be considered medical advice. Please speak with an appropriate healthcare professional when evaluating any wellness-related therapy.

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