Tier 4 — mechanistic

Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome

Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O'Neil L, White TA, Sinclair DA, Chini EN
Diabetes 2013 62(4):1084-93

Bibliography

PubMed
PMID 23172919
DOI
10.2337/db12-1139
Funding
Not stated in the available abstract.
Competing interests
Not stated in the available abstract.

Study snapshot

DesignIn vitro cell culture + in vivo animal study
ModelHuman cell lines (acetylation assays); obese mice (in vivo)
SampleNot applicable (preclinical)
InterventionApigenin (and quercetin) as pharmacological CD38 inhibitors, in vitro and in obese mice
DurationAcute/short-term preclinical dosing
EndpointsIntracellular NAD+ levels; Global protein acetylation (p53, RelA-p65); Glucose and lipid homeostasis in obese mice

What the study showed, in plain terms

This study identified apigenin as an inhibitor of CD38, an enzyme that breaks down NAD, a coenzyme cells need for energy production and repair. In cell cultures, apigenin raised NAD levels and changed protein acetylation patterns. In obese mice, giving apigenin raised NAD levels and improved several markers of glucose and fat metabolism.

Key findings

CD38 is the primary NAD-degrading enzyme (NADase) in mammals, and CD38 knockout mice have higher NAD levels and are protected against obesity and metabolic syndrome. The authors characterised apigenin and quercetin as pharmacological CD38 inhibitors: apigenin treatment of cell cultures decreased global protein acetylation, including of p53 and RelA-p65. In obese mice, apigenin administration increased NAD levels, decreased global protein acetylation, and improved several aspects of glucose and lipid homeostasis.

What this study can and cannot tell us

This is a preclinical study (cell culture and mouse) with no human data. Whether apigenin at achievable oral supplement doses meaningfully inhibits CD38 and raises NAD levels in humans has not been tested.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology