What is Apigenin? A Summary of Apigenin

Found in chamomile, this flavonoid has traditional uses that can be biochemically explained.

This active ingredient in chamomile tea has traditionally been used to ease anxiety and reduce stress. We investigate if the scientific studies support this traditional use and how it relates to aging.

What is apigenin?

Apigenin is a very common and widely distributed flavonoid in the plant kingdom. Flavonoids are a class of naturally occurring phytochemicals that are found in plant tissues. Plants use flavonoids to protect themselves from pathogens and radiation from the sun. Some of them even serve a role in attracting pollinating insects, such as bees, butterflies, and moths. Flavonoids are also used by plants to regulate their metabolism.

It is the aglycone of several naturally occurring glycosides, molecules that are connected to sugar molecules. It has been used in folk medicines for centuries as a way to treat anxiety and inflammation. Structurally, it is a solid crystalline with a yellow color, and it has been historically used to dye wool.

How much apigenin in chamomile tea?

Apigenin can be found in chamomile, which is normally drunk as a tea. It is obtained from the dried flowers of Matricaria chamomilla, an annual herb native to Western Asia and Europe. The plant has also been naturalized and grows wild in Australia and the United States.

The amount of apigenin in chamomile teas varies, with some containing significantly more chamomile than others. Teas prepared from chamomile generally have between 0.8% to 1.2% apigenin content.

What foods contain apigenin?

Apigenin can be found in many fruits, vegetables and herbs, including parsley, celery, celeriac, red and white sorghum, tarragon, yarrow, basil, rutabagas, oranges, kumquats, onions, wheat sprouts, thyme, spearmint, and cilantro.While many foods contain apigenin, parsley is a great way to get high amounts of it. 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.

While studies are limited, and the wide range of foods containing apigenin make it hard to estimate an accurate dietary intake, it is likely somewhere in the region of 20-25 mg per day. Of course, this could be higher, especially among people whose diets  are mostly or completely plant based.

Apigenin supplement

Of course, like most flavonoids, the supplement industry is more than ready to sell you apigenin as a dietary supplement. Typical doses start around 50mg, though higher doses are also offered.

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 chronically insomniac adults between 18-65 years old given chamomile flower extract, with at least 2.5 mg of apigenin [1]. The participants had experienced the condition for six months or longer and had a total daily sleep time of 6.5 hours or less.

The researchers found that there were no significant differences between the treatment and control groups. These included differences in 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 for people 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, allowing them to 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-blind 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 [12].

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.

Apigenin side effects

Apigenin is considered safe when consumed in normal amounts through a diet rich in fruits, vegetables and herbs. However, supplement doses tend to deliver a significantly higher amount of apigenin than would be generally consumed via dietary means. Higher doses of apigenin can cause stomach discomfort, and you should cease using it immediately and consult your doctor should this occur.

Some people can also be allergic to chamomile tea or apigenin, so again, if you experience adverse side effects, you should stop taking it.

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.

Disclaimer

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.

Author: Steve Hill

Publisher: Lifespan.io is a nonprofit advocacy organization and news outlet covering aging and rejuvenation research.

Literature

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[2] Mao, J. J., Xie, S. X., Keefe, J. R., Soeller, I., Li, Q. S., & Amsterdam, J. D. (2016). Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine, 23(14), 1735-1742.

[3] Amsterdam, J. D., Shults, J., Soeller, I., Mao, J. J., Rockwell, K., & Newberg, A. B. (2012). Chamomile (Matricaria recutita) may have antidepressant activity in anxious depressed humans-an exploratory study. Alternative therapies in health and medicine, 18(5), 44.

[4] Lee, J. H., Zhou, H. Y., Cho, S. Y., Kim, Y. S., Lee, Y. S., & Jeong, C. S. (2007). Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules. Archives of pharmacal research, 30(10), 1318-1327.

[5] Lapchak, P. A., & Boitano, P. D. (2014). Effect of the pleiotropic drug CNB-001 on tissue plasminogen activator (tPA) protease activity in vitro: Support for combination therapy to treat acute ischemic stroke. Journal of neurology & neurophysiology, 5(4).

[6] Huang, C. H., Kuo, P. L., Hsu, Y. L., Chang, T. T., Tseng, H. I., Chu, Y. T., … & Hung, C. H. (2010). The natural flavonoid apigenin suppresses Th1-and Th2-related chemokine production by human monocyte THP-1 cells through mitogen-activated protein kinase pathways. Journal of medicinal food, 13(2), 391-398.

[7] Huang, C. S., Lii, C. K., Lin, A. H., Yeh, Y. W., Yao, H. T., Li, C. C., Wang, T. S., & Chen, H. W. (2013). Protection by chrysin, apigenin, and luteolin against oxidative stress is mediated by the Nrf2-dependent up-regulation of heme oxygenase 1 and glutamate cysteine ligase in rat primary hepatocytes. Archives of toxicology, 87(1), 167–178. https://doi.org/10.1007/s00204-012-0913-4

[8] Telange, D. R., Patil, A. T., Pethe, A. M., Fegade, H., Anand, S., & Dave, V. S. (2017). Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 108, 36–49. https://doi.org/10.1016/j.ejps.2016.12.009

[9] Paredes-Gonzalez, X., Fuentes, F., Jeffery, S., Saw, C. L., Shu, L., Su, Z. Y., & Kong, A. N. (2015). Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharmaceutics & drug disposition, 36(7), 440–451. https://doi.org/10.1002/bdd.1956

[10] Camacho-Pereira, J., Tarragó, M. G., Chini, C. C., Nin, V., Escande, C., Warner, G. M., … & Chini, E. N. (2016). CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell metabolism, 23(6), 1127-1139.

[11] Schultz, M. B., & Sinclair, D. A. (2016). Why NAD+ declines during aging: It’s destroyed. Cell metabolism, 23(6), 965-966.

[12] Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., … & Chini, E. N. (2013). Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes, 62(4), 1084-1093.

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