Apigenin is a flavone found in seasoning herbs such as parsley and oregano; vegetables such as vine spinach, celery, and artichokes; and chamomile. It has been found to have antioxidant and anti-inflammatory properties, and its sources are used in traditional medical systems around the world1,2.

In an animal study, apigenin 40 mg/kg given before exposure to a neuroinflammatory toxin was shown to significantly suppress cytokines, chemokines, a neuroinflammation trigger known as glial activation, and subsequent neurodegeneration.

      In PPMS and RRMS animal models, apigenin at a dose of 40 mg/kg was associated with a significant reduction in severity of disease progression and relapse compared to controls. This included decreased immune cell infiltration and reduced demyelination in the CNS1.

      A novel form of apigenin known simply as “S3” was shown to restore maturation of key brain cells following administration of a toxic agent, and to promote remyelination in mice with demyelinating brain lesions4.

      When added to human nerve cells, apigenin inhibited neuroinflammation5. When added to the cells of MS patients, apigenin was found to be a strong inhibitor of autoimmune T-cell response6,7.

      In a set of preclinical experiments, apigenin was administered to both human cells and mouse models of genetic predisposition to Down’s syndrome (a genetic disorder generally associated with physical growth delays and mild to moderate intellectual disability). The cells cultured with 1-5 microM of apigenin had significantly reduced oxidative stress and improved antioxidant defense response. The mouse doses during pregnancy were 333-400 mg/kg/day of apigenin mixed with food, and did not result in significant increases in birth defects or offspring deaths. Further, apigenin significantly improved several developmental milestones in the neonates as well as, activation of pro-neurogenic genes and increased expression of the angiogenic and neurotrophic factors VEGFA and IL7 8.

      In humans, apigenin has been addressed in the context of pregnancy and nursing as a component of herbs such as chamomile, which is primarily consumed in “tea” form. While chamomile is “generally recognized as safe” (GRAS) for use in food by the U.S. Food and Drug Administration as a spice, seasoning, or flavoring agent, no data exist on safety of supplement/tea use in nursing mothers. Of note, chamomile has been safely and effectively used alone and with other herbs in infants for the treatment of colic, diarrhea, and other conditions, so the smaller amounts expected (but not demonstrated) in breastmilk are considered “likely not to be harmful” with usual maternal doses accessed through moderate tea consumption.

      The generally accepted apigenin dose for human supplementation is 50 mg/day.

References

1. Ginwala R, McTish E, Raman C, et al. Apigenin, a Natural Flavonoid, Attenuates EAE Severity Through the Modulation of Dendritic Cell and Other Immune Cell Functions. J Neuroimmune Pharmacol. Mar 2016;11(1):36-47. doi:10.1007/s11481-015-9617-x

2. Shankar E, Goel A, Gupta K, Gupta S. Plant flavone apigenin: An emerging anticancer agent. Curr Pharmacol Rep. Dec 2017;3(6):423-446. doi:10.1007/s40495-017-0113-2

3. Roboon J, Hattori T, Ishii H, et al. Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD(). J Neurochem. Jul 2021;158(2):311-327. doi:10.1111/jnc.15367

4. Su W, Matsumoto S, Banine F, et al. A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination. Glia. Feb 2020;68(2):263-279. doi:10.1002/glia.23715

5. Ginwala R, Bhavsar R, Moore P, et al. Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases. J Neuroimmune Pharmacol. Jun 2021;16(2):403-424. doi:10.1007/s11481-020-09933-8

6. Rahmati M, Ghannadian SM, Kasiri N, et al. Modulation of Th17 Proliferation and IL-17A Gene Expression by Acetylated Form of Apigenin in Patients with Multiple Sclerosis. Immunol Invest. Feb 2021;50(2-3):216-229. doi:10.1080/08820139.2020.1726381

7. Verbeek R, Plomp AC, van Tol EA, van Noort JM. The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and interferon-gamma production by murine and human autoimmune T cells. Biochem Pharmacol. Aug 15 2004;68(4):621-9. doi:10.1016/j.bcp.2004.05.012

8. Guedj F, Siegel AE, Pennings JLA, et al. Apigenin as a Candidate Prenatal Treatment for Trisomy 21: Effects in Human Amniocytes and the Ts1Cje Mouse Model. Am J Hum Genet. Nov 5 2020;107(5):911-931. doi:10.1016/j.ajhg.2020.10.001

9. Chamomile. Drugs and Lactation Database (LactMed(R)). 2006.