Apigenin is a flavonoid, a compound found in various plants, and is the aglycone of several naturally occurring glycosides. It is solid and crystalline in structure with a yellow color to it.
Apigenin can be found in many fruits and vegetables, but parsley, celery, celeriac, and chamomile, which is normally drank as a tea, are the most common sources. Dried parsley typically contains about 45 mg/gram, and dried chamomile flowers contain about 3-5 mg/gram of apigenin. The apigenin content of fresh parsley has been reported to be as high as 215.5 mg/100 grams. Green celery hearts can contain up to 19.1 mg/100 grams.
Apigenin in the context of insomnia
Chamomile tea has traditionally been used for relieving insomnia for many years. Its usage was so commonplace that researchers have studied its active molecules, which include apigenin.
A small study saw 34 adults aged between 18-65 years of old suffering from chronic insomnia given chamomile flower extract, with at least 2.5 mg of apigenin . The participants had experienced the condition for six months or longer and had a total daily sleep time of 6.5 or less.
The researchers found that there were no significant differences between the treatment and control groups. These included differences to total sleep time, sleep efficiency, sleep latency, wake after sleep onset, sleep quality, and number of times that they awakened during sleep.
While it did not appear to have an impact on sleep quality itself, the researchers did observe a modest improvement in daytime functioning. They concluded that chamomile may be useful to improve daytime functioning in those suffering from insomnia.
Apigenin for anxiety and depression
Chamomile has also been traditionally used for treating anxiety and depression. A randomized, long-term clinical trial for the treatment of generalized anxiety disorder (GAD), was initiated in 2016. The trial saw the administration of 1500 mg (500 mg capsules three times daily) of chamomile extract to trial participants.
179 participants initially took part in an open-label phase, a phase of the trial in which information is not withheld from trial participants so that they know what they are taking. In the second phase, 93 participants were randomized to either 26 weeks of continued chamomile treatment or given a placebo in a double-blinded study.
Participants taking chamomile extract were shown to have significantly lower anxiety levels than participants in the placebo group. The chamomile group also showed a reduction of body weight and mean arterial blood pressure. Chamomile appeared to be safe and had a significant effect on GAD symptoms.
A 2012 study saw chamomile extract used for the treatment of GAD in a randomized, double-blind, placebo-controlled trial. Chamomile extract with a 1.2% apigenin content was administered to trial participants with anxiety; co-morbid depression, or anxiety with a history of depression; and anxiety with no current or past depression.
The 57 participants were given either chamomile extract or a placebo. The results showed a significant reduction in total Hamilton Depression Rating Scale scores with chamomile treatment. This suggests that chamomile extract may have an antidepressant effect.
This is good news, as research shows that depression can have a negative impact on the rate at which we age. In fact, according to the popular biological aging clock GrimAge, a clock that can accurately predict life expectancy, a person’s GrimAge is accelerated in major depression.
Anti-inflammatory properties of apigenin
Historically, chamomile tea has been used as a way to reduce inflammation, so it is no surprise that apigenin promotes multiple anti-inflammatory pathways, including p38/MAPK and PI3K/Akt, and that apigenin prevents IKB kinase degradation, which proceeds proinflammatory NF-κB activation and reduces COX-2 activity [4-6].
Apigenin has been shown to increase the expression of antioxidant enzymes, including GSH-synthase, catalase, and superoxide dismutase (SOD) to combat cellular oxidative and electrophilic stress. Our own white blood cells produce SOD and other reactive oxygen species to kill bacteria. Apigenin boosts the expression of phase II enzyme-encoding genes by blocking the NADPH oxidase complex and its downstream target inflammatory genes via increasing expression of nuclear translocation of Nrf-2 [7-9].
Apigenin and NAD+
In the context of aging and metabolism, apigenin and quercetin are both shown to inhibit the activity of CD38 [10-11]. CD38 is an enzyme that consumes nicotinamide adenine dinucleotide (NAD+) in ever-increasing amounts as we get older. NAD+ is a coenzyme found in all living cells and is essential for cellular function, DNA repair, and life.
Animal studies have shown that mice bred to be deficient in CD38 enjoy increased protection from mitochondrial dysfunction and are resistant to diabetes as they age. This protective action is regulated via the mitochondrial sirtuin SIRT3. Mice treated with apigenin show an increased level of NAD+ and are resistant to the effects of high-fat diets .
Given that CD38 actively degrades both NAD+ and NMN, it may be a useful approach to use CD38 inhibitors such as apigenin to increase NAD+ levels rather than try to boost them with precursors. In other words, it is better to treat the cause of NAD+ loss rather than trying to compensate for it. You can learn more about the intertwined nature of NAD+, CD38, and senescence here.
The future of apigenin
Despite there being a number of interesting animal studies on apigenin, there is currently a lack of human data beyond cell studies. There is no doubt more to learn about apigenin, including its possible utility as a senolytic or senomorphic, but more research is needed before we can make any conclusions regarding the geroprotective effects of apigenin.
This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse apigenin supplements nor any product or supplement vendor, and all discussion here is for scientific interest.
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