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Apigenin: a powerful flavonoid in your chamomile tea

Chamomile was always recognized as one of the most powerful medicinal herbs throughout the centuries. The ancient Greeks considered chamomile to have remarkable healing and soothing properties. Egyptians thought the plant to be sacred and considered it a gift from the God of the Sun.

greek chamomile tea

Greek Chamomile

While ancient populations were using chamomile herbal infusions empirically (based only on experience and observation) today we know that chamomile’s medicinal properties stem from its high enrichment in terpenoids and flavonoids. Flavonoids are plant-derived compounds that have numerous beneficial effects on health and well-being. To name only a few, flavonoids are considered to have antioxidant, anti-tumor, anti-inflammatory, and anti-diabetic properties.

Of all the flavonoids, Apigenin is one of the most studied bioactive flavones. It is found mainly in vegetables, citrus fruits, herbs, tea, and wine. Chamomile is one of the richest natural sources of apigenin (840 mg/ 100 g) while Chamomile herbal infusions (where dried flower is infused into water) contain 0.8-1.2% apigenin mostly in the form of apigenin-7-O-glucoside.

Apigenin is backed by several in vivo studies and ingestion of apigenin was shown to have favorable effects in many medical diseases and conditions including diabetes, memory impairments and Alzheimer’s disease, several types of cancer, inflammation, depression, and insomnia. 

Free form Apigenin has been shown to lack bioavailability, meaning its absorption and distribution in tissues within the body is low. On the contrary, apigenin-7-O-glucoside which is the form found mainly in Chamomile herbal infusions exhibits better absorption and bioavailability.

Although research on Apigenin is still in infancy, it has become clear that exhibits remarkable benefits for several aspects of human health such as sleep, libido, anxiety, mood, weight management, blood sugar, memory, and cognitive function.

    Apigenin for sleep, stress, mood, and relaxation

    chamomile tea for sleep relaxation and mood

    Chamomile tea with lavender, passionflower, and valerian root for sleep.

    Having trouble sleeping? Do you feel this unbearable muscle and nerve tension along with anxiety that keeps you up at night? Many people do. In fact, approximately 30% to 40% of adults in the United States report symptoms of insomnia each year, whereas anxiety disorders (which are the most common mental illness in the U.S.) are affecting 40 million adults in the United States (that is 19.1% of the population every year). 

    Apigenin has been shown to induce sedation and relieve symptoms of depression and anxiety in animals.[8–10]Furthermore, in several human trials, chamomile extract  has been proven effective in reducing the symptoms of generalized anxiety disorder (GAD; an anxiety disorder that affects 6.8 million adults or 3.1% of the U.S. population) and depression (An estimated 21.0 million adults in the United States had at least one major depressive episode in 2020).[11,12]The Chamomile extract used was standardized to a content of 1.2% apigenin. The volunteers had anxiety with co-morbid depression, or anxiety with history of depression, or anxiety with no current or past depression and long term chamomile extract consumption was shown to improve all participants' mood considerably.[11] The antidepressant effects of chamomile are mostly attributed to the apigenin content.[13] 

    SUMMARY

    • Apigenin has mild sedative properties
    • Apigenin may relieve depression and anxiety
    • Chamomile may relieve symptoms of generalized anxiety disorder 

      Apigenin for gut health

      chamomile tea for gut health stomach issues

      The Chian herbal tea: Chamomile tea with mahlepi and mastic for gut health.

      Children and older adults commonly suffer from gut disorders and indigestion that may require pharmacologic or even, in rare occasions, surgical treatments. Chamomile has been known for centuries to be one of the most beneficial herbs for gut health. Although no clinical trials have examined the gastrointestinal effects of chamomile alone, three trials have examined different chamomile preparations for children with gastrointestinal diseases. The effects of a powdered herbal tea preparation containing extracts of M. chamomilla, vervain (Verbena officinalis), licorice (Glycyrrhiza glabra), fennel (Foeniculum vulgare) and balm-mint (Melissa officinalis) was tested as a treatment for infantile colic (a benign process in which an infant has paroxysms of inconsolable crying for more than three hours per day, more than three days per week, for longer than three weeks). After 7 days, drastic colic improvement was shown in the herbal tea group. In another randomized, double-blind, placebo-controlled trial, a standardized herbal preparation containing chamomile, fennel and balm-mint given daily for 1 week reduced crying time among breastfed colicky infants compared with a placebo preparation. Results were observed within 4 days of treatment. Finally, the effects of a chamomile extract and apple pectin preparation were tested in children of age 0.5–5.5 years with acute diarrhea. The children received either the chamomile/pectin or a placebo for 3 days. The diarrhea ended sooner for children in the group treated with chamomile and pectin, than in the placebo group.[14,15]

      Finally, it is now common knowledge that your body is full of bacteria, viruses and fungi. In fact, bacteria are more, in number, than all of your cells. Those micro-organims co-existing with you, are collectively known as the microbiome. While some bacteria are associated with disease, others are extremely important for your immune system, heart, weight and many other aspects of health. Apigenin was found to have a profound effect on the gut microbiome, altering the populations of bacteria in the gut. Specifically, apigenin was shown to inhibit growth of both Enterococcus caccae and B. galacturonicus (Enterococci are gram negative bacteria strains residing in human gut that can cause several diseases when found in other places of the body). Interestingly, the ability of apigenin to influence growth of the gut bacteria was individualistic, meaning that some species were affected and others were not. For example L. rhamnosus GG and B.catenulatum, two beneficial for human health strains, were not affected by apigenin.[16]

      SUMMARY

      • Most studies are done on chamomile extract in combination with other herbs
      • Children with gastrointestinal diseases have been the treated population of most studies
      • Chamomile may relieve gastrointestinal symptoms 
      • Apigenin can favorably alter the gut microbiome

       

      Apigenin for brain health and performance

      chamomile tea apigenin brain health

      Numerous In vivo studies (mainly on animal participants) have demonstrated that apigenin possesses impressive neuroprotective and nootropic properties. Animals consuming apigenin were protected against Alzheimer’s disease (AD; a neurodegenerative disease that leads to dementia and cognitive decline) and amnesia (memory loss).[1,2] Interestingly, Apigenin was not only shown to be protective against inflammation and nerve apoptosis (essentially nerve death due to aging or inflammation) of the central nervous system, but also to induce a protein called BDNF (Brain Derived Neurotropic Factor) which is involved in brain changes related to learning and memory.[3,4] In fact, long-term memory has been shown to be affected and improved the most.[5] To demonstrate the memory-enhancing activity of Chamomile, rats in which memory loss was induced by scopolamine (an anticholinergic drug frequently used in research to induce transient cognitive deficits and memory loss that imitate human dementia)  were given a chamomile extract. Impressively enough, chamomile extract could reverse the memory deficits that had been induced by scopolamine. These effects were attributed to the high neuro-antioxidant activity of chamomile.[6] In human studies, patients with AD and other neurodegenerative diseases (namely parkinson’s disease, multiple sclerosis) were given a formulation containing apigenin which succeeded in stabilizing their disease and improving cognitive function upon long-term administration (every 12 h for 24 months).[7]

      SUMMARY

      • Most studies derive from animal participants
      • Apigenin has neuroprotective and nootropic properties
      • Apigenin improves long term memory and memory retention
      • Chamomile acts as a neuro-antioxidant in animals and humans

       

      Author: Michail Spanos, MD, Post Doctoral Research Fellow at Mass General Hospital, Harvard Medical School
      References 
      1. Zhao L, Wang JL, Wang YR, Fa XZ. Apigenin attenuates copper-mediated β-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model. Brain Res 2013;1492. [DOI: 10.1016/j.brainres.2012.11.019].
      2. Zhao L, Wang JL, Liu R, Li XX, Li JF, Zhang L. Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer’s disease mouse model. Molecules 2013;18. [DOI: 10.3390/molecules18089949].
      3. Sharma P, Sharma S, Singh D. Apigenin reverses behavioural impairments and cognitive decline in kindled mice via CREB-BDNF upregulation in the hippocampus. Nutr Neurosci 2020;23. [DOI: 10.1080/1028415X.2018.1478653].
      4. Balez R, Steiner N, Engel M, et al. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci Rep 2016;6. [DOI: 10.1038/srep31450].
      5. Popović M, Caballero-Bleda M, Benavente-García O, Castillo J. The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats. J Psychopharmacol 2014;28. [DOI: 10.1177/0269881113512040].
      6. Alibabaei Z, Rabiei Z, Rahnama S, Mokhtari S, Rafieian-Kopaei M. Matricaria chamomilla extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Biomed Aging Pathol 2014;4. [DOI: 10.1016/j.biomag.2014.07.003].
      7. De Font-Réaulx Rojas E, Dorazco-Barragán G. Clinical stabilisation in neurodegenerative diseases: Clinical study in phase II. Rev Neurol 2010;50. [DOI: 10.33588/rn.5009.2009546].
      8. Weng L, Guo X, Li Y, Yang X, Han Y. Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice. Eur J Pharmacol 2016;774. [DOI: 10.1016/j.ejphar.2016.01.015].
      9. Zanoli P, Avallone R, Baraldi M. Behavioral characterisation of the flavonoids apigenin and chrysin. Fitoterapia 2000;71. [DOI: 10.1016/S0367-326X(00)00186-6].
      10. Li R, Zhao D, Qu R, Fu Q, Ma S. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neurosci Lett 2015;594. [DOI: 10.1016/j.neulet.2015.03.040].
      11. Amsterdam JD, Shults J, Soeller I, Mao JJ, Rockwell K, Newberg AB. Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: An exploratory study. Altern Ther Health Med 2012;18.
      12. Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine 2016;23. [DOI: 10.1016/j.phymed.2016.10.012].
      13. Nakazawa T, Yasuda T, Ueda J, Ohsawa K. Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test. Biol Pharm Bull 2003;26. [DOI: 10.1248/bpb.26.474].
      14. Anheyer D, Frawley J, Koch AK, et al. Herbal medicines for gastrointestinal disorders in children and adolescents: A systematic review. Pediatrics 2017;139.
      15. S  de la M, S B-O, M H, F H. [Double-blind comparison of an apple pectin-chamomile extract preparation with placebo in children with diarrhea]. Arzneimittelforschung 1997;47.
      16. Wang M, Firrman J, Zhang L, et al. Apigenin impacts the growth of the gut microbiota and alters the gene expression of enterococcus. Molecules 2017;22. [DOI: 10.3390/molecules22081292].
      17. Zhao L, Wang JL, Wang YR, Fa XZ. Apigenin attenuates copper-mediated β-amyloid neurotoxicity through antioxidation, mitochondrion protection and MAPK signal inactivation in an AD cell model. Brain Res 2013;1492. [DOI: 10.1016/j.brainres.2012.11.019].
      18. Zhao L, Wang JL, Liu R, Li XX, Li JF, Zhang L. Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer’s disease mouse model. Molecules 2013;18. [DOI: 10.3390/molecules18089949].
      19. Sharma P, Sharma S, Singh D. Apigenin reverses behavioural impairments and cognitive decline in kindled mice via CREB-BDNF upregulation in the hippocampus. Nutr Neurosci 2020;23. [DOI: 10.1080/1028415X.2018.1478653].
      20. Balez R, Steiner N, Engel M, et al. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci Rep 2016;6. [DOI: 10.1038/srep31450].
      21. Popović M, Caballero-Bleda M, Benavente-García O, Castillo J. The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats. J Psychopharmacol 2014;28. [DOI: 10.1177/0269881113512040].
      22. Alibabaei Z, Rabiei Z, Rahnama S, Mokhtari S, Rafieian-Kopaei M. Matricaria chamomilla extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Biomed Aging Pathol 2014;4. [DOI: 10.1016/j.biomag.2014.07.003].
      23. De Font-Réaulx Rojas E, Dorazco-Barragán G. Clinical stabilisation in neurodegenerative diseases: Clinical study in phase II. Rev Neurol 2010;50. [DOI: 10.33588/rn.5009.2009546].
      24. Weng L, Guo X, Li Y, Yang X, Han Y. Apigenin reverses depression-like behavior induced by chronic corticosterone treatment in mice. Eur J Pharmacol 2016;774. [DOI: 10.1016/j.ejphar.2016.01.015].
      25. Zanoli P, Avallone R, Baraldi M. Behavioral characterisation of the flavonoids apigenin and chrysin. Fitoterapia 2000;71. [DOI: 10.1016/S0367-326X(00)00186-6].
      26. Li R, Zhao D, Qu R, Fu Q, Ma S. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neurosci Lett 2015;594. [DOI: 10.1016/j.neulet.2015.03.040].
      27. Amsterdam JD, Shults J, Soeller I, Mao JJ, Rockwell K, Newberg AB. Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: An exploratory study. Altern Ther Health Med 2012;18.
      28. Mao JJ, Xie SX, Keefe JR, Soeller I, Li QS, Amsterdam JD. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. Phytomedicine 2016;23. [DOI: 10.1016/j.phymed.2016.10.012].
      29. Nakazawa T, Yasuda T, Ueda J, Ohsawa K. Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test. Biol Pharm Bull 2003;26. [DOI: 10.1248/bpb.26.474].
      30. Anheyer D, Frawley J, Koch AK, et al. Herbal medicines for gastrointestinal disorders in children and adolescents: A systematic review. Pediatrics 2017;139.
      31. S  de la M, S B-O, M H, F H. [Double-blind comparison of an apple pectin-chamomile extract preparation with placebo in children with diarrhea]. Arzneimittelforschung 1997;47.
      32. Wang M, Firrman J, Zhang L, et al. Apigenin impacts the growth of the gut microbiota and alters the gene expression of enterococcus. Molecules 2017;22. [DOI: 10.3390/molecules22081292].
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