Because apigenin is unstable and poorly bioavailable in isolation, much of what is known about apigenin’s clinical effect in humans comes from studies using the plants or foods that it comes from.^{[44][3][45][46][47]} The formulation of the supplement may improve apigenin’s bioavailability, and some research has explored preparations such as enteric coated pellets^[48] and carbon nanopowders.^[5] However, preclinical studies examining bioavailability in both humans and animals using apigenin in an isolated form are typically done in a tightly controlled setting that does not reflect everyday use.^[49][5][50]

Preclinical (animal) evidence suggests that apigenin may function as an antioxidant, anti-inflammatory, and/or means to resist pathogenic infection.^{[33][26][51][52]} Apigenin’s anti-inflammatory effects (typically seen at concentrations of 1–80 micromolar) may be derived from its ability to suppress the activity of some enzymes (NO-synthase and COX2) and cytokines (interleukin 4, interleukin 6, interleukin 8, interleukin 17A, and TNF-α) that are known to be involved in inflammatory and allergic responses.^{[22][23][24][25][26][27][28]} On the other hand, apigenin’s antioxidant properties (seen at concentrations of 100–279 micromolar/L) may be due in part to its ability to scavenge free radicals and protect DNA from free radical damage.^[19][20][21] Apigenin may also serve as an adjunctive to stave off the proliferation of parasites (at concentrations of 5–25 μg/mL), microbial biofilms (at a concentration of 1 millimolar), and viruses (at concentrations of 5–50 micromolar), suggesting it may have the potential to improve resistance to infection.^[51][52][53]

Though there is little clinical evidence available on apigenin’s effect on immune health, what evidence there is does suggest some anti-inflammatory,^[42][54] antioxidant,^[55][56] and infection-resistance^[57] benefits. It should be noted, however, that all clinical evidence explores apigenin as a part of its source (i.e., plants, herbs), so these effects cannot be attributed to apigenin alone.

In preclinical (animal and cell) studies, apigenin has shown effects on anxiety and brain cell activity.^{[16][15][17][18]} In a mouse study, doses of 3–10 mg/kg of body weight reduced anxiety without causing sedation.^[15] Neuroprotective effects, caused by an increased mitochondrial capacity, have also been observed in animal studies at concentrations of 1–33 micromolar.^[18][16]

Few clinical studies show similar effects in humans. Two of the most promising studies examined apigenin as a constituent of chamomile (Matricaria recutita) for anxiety and migraine. When participants with codiagnoses of anxiety and depression were given 200–1,000 mg of chamomile extract per day for 8 weeks (standardized to 1.2% apigenin), the participants reported improvements in anxiety and depression symptoms.^[58] In a similar crossover trial, participants with migraine experienced a reduction in pain, nausea, vomiting, and light/noise sensitivity 30 minutes after application of a chamomile oleogel (0.233 mg of apigenin per gram).^[40]

Apigenin might reduce levels of cortisol, the stress hormone. When human adrenal cells (in vitro) were exposed to flavonoid mixtures that included apigenin as a component in a range of concentrations of 12.5–100 micromolar, cortisol production decreased by up to 47.3% compared to control cells.^[31][32]

In mice, apigenin extracted from the plant Cephalotaxus sinensis, a member of the plum yew family, increased the physiologic response to insulin.^[29] These results have not yet been replicated in humans; in a study that gave participants a black pepper beverage that contained apigenin and a wheat bread challenge meal, blood glucose and insulin were no different from the control beverage group.^[59]

Reproductive hormones such as testosterone and estrogen may also be affected by apigenin. In preclinical (animal) studies, apigenin modified enzyme receptors and activity in a way that suggests it could potentially affect testosterone activity, even at relatively low concentrations (5–10 micromolar).^[60][61]

Breast cancer cells exposed to apigenin at a concentration of 20 micromolar for 72 hours showed inhibited proliferation through control of estrogen receptors.^[30] Similarly, when ovarian cells were exposed to apigenin, aromatase activity was inhibited, and this is thought to be a possible mechanism in the prevention and treatment of breast cancer.^[62] It is still unclear, however, how these effects would translate into an oral dose for human consumption.

Because apigenin has low bioavailability and stability in isolation, human research tends to focus on its consumption through plants, herbs, and their extracts. Bioavailability and subsequent absorption, even from plant and food sources, may also vary from individual to individual and because of the source it’s derived from.^[63][44] Examining the dietary flavonoid intake (including apigenin, which is subclassed as a flavone) and excretion alongside the risk of various conditions may therefore be the most practical means of assessment. One large observational study, for example, found that of all the dietary flavonoids, the intake of apigenin was associated with a 5% reduction in the risk of hypertension among the participants who consumed the highest amounts compared to the participants who consumed the least.^[64] It is possible, however, that there are other differences that might explain this association, such as income, which can affect health status and access to care, leading to a reduced risk of hypertension. One randomized controlled trial found no effect of the consumption of apigenin-rich foods (onion and parsley) on biomarkers related to hypertension (e.g., aggregation of platelets (clotting) and precursors of this process).^[65]