Apigenin, also known as 4′,5,7-trihydroxyflavone [1], is a flavonoid from fruits and vegetables, including garlic, celery, onions, oranges, and chamomile [2]. You can read more on other natural sources of apigenin here.
Apigenin is principally known for its antioxidant properties [3], but it also presents hypoglycemic [4], anti-inflammatory [5], and cytostatic and cytotoxic properties for various cancer cells [6]. Finally, apigenin possesses antidepressant effects, and its anxiolytic properties will be the focus of this article [7].
Possible mechanisms of action
Numerous research suggests serotoninergic, noradrenergic, and dopaminergic systems dysfunction in major depression disorder and anxiety disorders [8]. In depressive animals, apigenin improves serotonin, dopamine, and epinephrine levels, which are altered [9,10], and its observed antidepressant activity may result from its effect on α-adrenergic, dopaminergic, and serotonergic receptors [11-13]. Additionally, apigenin regulates the cAMP-CREB-BDNF signaling pathway and N-methyl-D-aspartate (NMDA) receptors [14,15]. As a result, it plays a role in synaptic plasticity, cognitive function, and mood behavior.
Recent research suggests that alterations in the monoaminergic system are linked to anxiety [8,16]. Anxiety, then, triggers inflammatory processes, such as high levels of IL-6, IL-1β, and TNF-α. Interestingly, apigenin increases monoamine levels in the brain [16] by inhibiting monoamine oxidase A [17]. It also inhibits proinflammatory cytokine production [18] and modulates γ-aminobutyric acid (GABA)-A receptors [15].
Efficacy in the treatment of anxiety
Anxiety-like behavior test in animal models
Several rodent (mice and rats) studies used the elevated plus maze test and successfully identified apigenin's anxiolytic effects [16,19,20]. However, another study in rats using the dark-light test failed to detect any anxiolytic activity [21].
Efficacy in clinical trials
A recent systematic review analyzed the effects of oral chamomile on anxiety from 10 clinical trials [22], apigenin being one of chamomile’s principal active compounds [23]. Oral chamomile’s anxiolytic efficacy was evaluated in patients with generalized anxiety disorder (moderate to severe) [24-27], primary insomnia [28], cancer [29], menopause [30], menstrual-related mood disorders [31], and dysmenorrhea [32]. The last study involved an elderly population [33]. Most clinical trials used chamomile capsules with dosages ranging from 250 mg to 2 g daily. In the others, the intervention consisted of one or two cups of chamomile tea daily [32-34]. Finally, the clinical trials’ duration ranged from two to 26 weeks.
Most of these studies concluded that daily chamomile consumption effectively reduced anxiety [24-27]. In generalized anxiety disorder, chamomile also improved patients’ health, blood pressure, and weight [26]. If generalized anxiety disorder was associated with depression, chamomile also reduced depressive symptoms [27]. The trial results from patients with insomnia showed only a moderate effect size, which may be related to their short study period [28]. In postmenopausal women, chamomile reduced anxiety [30,32]. However, in cancer patients, chamomile had no anxiolytic effects [29].
Safety
Apigenin does not cause severe toxicity at high doses (up to 5000 mg/kg) in mice and rats [35]. In vivo, it shows no carcinogenic or mutagenic effects [36,37].
Apigenin in chamomile presents no side effects [25,26,29,31]; however, chamomile contains various compounds besides apigenin. For instance, chamomile consumption during pregnancy results in a shorter height of the newborn [38,39]. It might also induce spontaneous abortion [40] as chamomile possesses oxytocic and uterine effects. Chamomile extracts contain allergenic proteins, potentially resulting in immediate-type hypersensitivity reactions [41,42]. Finally, chamomile’s compounds may interact with medication. For instance, a coumarin derivative of chamomile might interfere with antiplatelet and anticoagulant drugs, such as aspirin, and increase the sedative effects of opioid analgesics [43].
Conclusion
Apigenin, a flavonoid found in various fruits, vegetables, and chamomile, exhibits anxiolytic properties through its effects on neurotransmitter systems and inflammatory pathways. Preclinical studies demonstrate its potential to reduce anxiety-like behavior, although results vary depending on the test model used. Clinical trials on chamomile, which contains apigenin, suggest its efficacy in alleviating anxiety, particularly in generalized anxiety disorder and menopause-related anxiety. While apigenin appears safe at high doses, chamomile consumption may pose risks in certain populations, such as pregnant women and individuals taking anticoagulants. Further research is necessary to isolate apigenin's specific role in anxiety treatment and its long-term safety profile.
References
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