Apigenin (4',5,7-trihydroxyflavone) is a flavone found abundantly in chamomile (Matricaria chamomilla), parsley, celery, peppermint, and many other plants. It has attracted scientific interest for several reasons: it binds GABA-A receptors as a partial positive allosteric modulator, producing anxiolytic and mildly sedative effects through the same receptor class as benzodiazepines but with a different pharmacological profile; it is a potent inhibitor of CD38, an enzyme that consumes NAD+ and is implicated in the NAD+ decline of aging; and it has antiestrogenic, anti-inflammatory, and potential anti-cancer activities.
Chamomile tea has been used as a calming bedtime beverage across many cultures for centuries, and apigenin is widely considered the primary bioactive responsible for this traditional use. The GABA-A modulation at physiologically achievable concentrations of apigenin (particularly in high-dose extracts or supplements) provides a plausible mechanism for anxiolytic and sleep-enhancing effects observed in both animal models and human chamomile tea trials.
In the longevity research field, apigenin has recently attracted attention as a CD38 inhibitor. CD38 is a multifunctional enzyme expressed on immune cells and in many tissues that consumes NAD+ (specifically converting it to ADP-ribose and cADPR). NAD+ levels decline significantly with aging, and this decline is considered a significant contributor to mitochondrial dysfunction and metabolic deterioration in aging. CD38 has been identified as a major NAD+ consumer, and its inhibition — by apigenin and by quercetin, another flavonoid — has been proposed as a mechanism to preserve NAD+ levels, potentially complementary to NMN or NR supplementation.
Apigenin has a generally excellent safety profile at food doses and typical supplemental amounts, though the GABA-A modulating activity warrants attention in combination with benzodiazepines, alcohol, or other CNS depressants.