Due to apigenin’s stability and bioavailability issues, much of what is known about apigenin’s clinical effect in humans comes from studies using the plants or foods that it comes from.^{[3][9][45][46][47]} Delivery format may also improve apigenin’s bioavailability, and some research has explored preparations such as enteric coated pellets^[48] and carbon nanopowders.^[4] 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 would be prohibitive to everyday use.^[49][4][50]

Preclinical evidence suggests that apigenin may serve as an anti-oxidant, anti-inflammatory, and/or means to resist pathogenic infection.^{[34][27][51][52]} Apigenin’s anti-inflammatory effects (typically seen at 1-80 µM concentrations) may be derived from its ability to suppress the activity of some enzymes (NO-synthase and COX2) and cytokines (interleukins 4, 6, 8, 17A, TNF-α) that are known to be involved in inflammatory and allergic responses.^{[23][24][25][26][27][28][29]} On the other hand, apigenin’s anti-oxidant properties (100-279 µM/L) may be due in part to its ability to scavenge free radicals and protect DNA from free radical damage.^[20][21][22] Apigenin may also serve as an adjunctive to stave off the proliferation of parasites (5-25 μg/ml), microbial biofilms (1 mM), and viruses (5-50μM), suggesting it may have potential to improve resistance to infection.^[51][52][53]

Though there is little clinical evidence available on apigenin’s interactions with immune health, what is present does suggest some anti-inflammatory^[43][54], anti-oxidant^[55][56], and infection resistance^[57] benefits through improvements in antioxidant enzyme activity, signs of aging, atopic dermatitis, chronic periodontitis, and lowered risk for type II diabetes. It should be noted, however, that all clinical evidence explores apigenin as a constituent of its source (e.g., plants, herbs, etc.) or as an added ingredient, so these effects cannot be attributed to apigenin alone.

In preclinical (animal and cell) studies, apigenin has exhibited effects on anxiety, neuroexcitation, and neurodegeneration.^{[17][16][18][19]} In a mouse study, dosages of 3–10 mg/kg of body weight produced reductions in anxiety without causing sedation.^[16] Neuroprotective effects, conferred through increased mitochondrial capacity, have also been observed in animal studies (1–33 μM).^[19][17]

Few clinical studies translate these results into humans. Two of the most promising studies examined apigenin as a constituent of chamomile (Matricaria recutita) for anxiety and migraine. When participants with co-diagnoses of anxiety and depression were given 200–1,000 mg of chamomile extract per day for 8 weeks (standardized to 1.2% apigenin), researchers observed improvements in self-reported anxiety and depression scales.^[58] In a similar cross-over 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/g of apigenin).^[41]

Apigenin may also be able to exert positive physiologic responses by reducing cortisol, the stress hormone. When human adrenocortical cells (in vitro) were exposed to a range of 12.5–100 μM flavonoid mixtures that included apigenin as a component, cortisol production decreased by up to 47.3% compared to control cells.^[32][33]

In mice, apigenin extracted from the plant Cephalotaxus sinensis of the Plum Yew family showed some anti-diabetic properties by increasing physiologic response to insulin.^[30] These results have not yet been replicated in humans, though 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 studies, apigenin modified enzyme receptors and activity in a way that suggests it could potentially affect testosterone activity, even at relatively low (5–10 μM) amounts.^[60][61]

At 20 μM, breast cancer cells exposed to apigenin for 72 hours showed inhibited proliferation through control of estrogen receptors.^[31] Similarly, when ovarian cells were exposed to apigenin (100 nM for 48 hours) researchers observed an inhibition of aromatase activity, which 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.

The bioavailability and stability issues of the flavonoid apigenin in isolation tends to result in human research with a focus on consumption through plants, herbs, and their extracts. Bioavailability and subsequent absorption, even from plant and food sources, may also vary per individual and the source it’s derived from.^[63][3] Studies examining dietary flavonoid intake (including apigenin, which is sub-classed as a flavone) and excretion alongside risk for disease, may therefore be the most practical means of assessment. One large observational study, for example, found that of all the dietary flavonoid subclasses, intake of apigenin alone carried a 5% reduction in risk for hypertension for participants who consumed the highest amounts, compared to participants consuming the lowest.^[64] It is possible though, 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 hypertension risk. One randomized experiment found no effect between consumption of apigenin rich foods (onion and parsley) on biomarkers related to hypertension (e.g., aggregation of platelets and precursors of this process).^[65] The caveat here is that plasma apigenin could not be measured in the participants’ blood, so longer term and varied consumption or perhaps even different approaches, such as outcome measures that don’t solely focus on platelet aggregation, may be needed in order to understand the potential effects.