Letter to the editor

Recent insights into the biological functions of apigenin

Jae Kwang Kim1, Sang Un Park2[*]

1Division of Life Sciences and Bio-Resource and Environmental Center, Incheon National University, Incheon 22012, Korea

2Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea

EXCLI J 2020;19:Doc984


Dear Editor,

Apigenin (4′,5,7-trihydroxyflavone) belongs to the group of flavonoids positioned on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) and is most extensively allocated in herbs, vegetables, and fruits (Shankar et al., 2017[46]; Sharma et al., 2019[47]). Biosynthetically, apigenin is obtained from the phenylpropanoid pathway and also from the flavone synthesis pathway (Forkmann, 1991[12]) The pathway of phenylpropanoid begins from the aromatic amino acids L-phenylalanine or L-tyrosine, both products of the shikimate pathway (Herrmann, 1995[18]).

In several recent studies, it has been shown that apigenin has a number of valuable bioactive functions, including antibacterial, antiviral, antiproliferative, anti-inflammatory, antioxidant, antiangiogenic, and anticancer activities (Kowalczyk et al., 2017[25]; Nabavi et al., 2018[35]; Ghițu et al., 2019[14]).

From the results of several in vivo and in vitro studies and clinical trials, apigenin has been shown to be an effective curative treatment for rheumatoid arthritis, autoimmune disorders, Parkinson's disease, Alzheimer's disease, and several types of cancers (Tang et al., 2017[51]; Salehi et al., 2019[43]). Here, we summarize the key findings of the biological and pharmacological actions of apigenin (Table 1(Tab. 1); References in Table 1: Ahmad et al., 2019[1]; Ai et al., 2017[2]; Amiri et al., 2018[3]; Britto et al., 2017[4]; Charalabopoulos et al., 2019[5]; Chen et al., 2017[7], 2019[8], 2020[6]; Choi et al., 2018[9]; Dean et al., 2018[10]; Feng et al., 2017[11]; Ganai, 2017[13]; Han et al., 2017[15]; Hassan et al., 2017[16]; He et al., 2020[17]; Huang et al., 2020[19]; Jiang et al., 2018[20]; Jiao et al., 2019[21]; Jing et al., 2019[22]; Kang et al., 2018[23]; Ketkaew et al., 2017[24]; Lee et al., 2019[26]; Li et al., 2017[28], 2019[29], 2020[27]; Liu et al., 2018[30]; Lu et al., 2019[31]; Malik et al., 2017[32]; Mirzoeva et al., 2018[33]; Mrazek et al., 2019[34]; Nelson et al., 2017[36]; Pang et al., 2019[37]; Qiu et al., 2019[38]; Quan et al., 2020[39]; Rašković et al., 2017[40]; Ren et al., 2018[41]; Safari et al., 2018[42]; Sánchez-Marzo et al., 2019[44]; Sang et al., 2017[45]; Sharma et al., 2018[48]; Siddique and Jyoti, 2017[49]; Stump et al., 2017[50]; Thangaiyan et al., 2018[52]; Tong et al., 2019[53]; Wang et al., 2017[54], 2018[56], 2019[55]; Wu et al., 2017[57]; Xu et al., 2018[58]; Zare et al., 2019[59]; Zhang et al., 2017[61], 2018[63], 2019[62], 2020[60]; Zhao et al., 2019[64]; Zhong et al., 2017[65], 2018[66]; Zhou et al., 2019[67]).


This research was supported by Golden Seed Project (213006051WTE11) funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA), the Ministry of Oceans and Fisheries (MOF), the Rural Development Administration (RDA), and the Korea Forest Service (KFS), Republic of Korea.

Conflict of interest

The authors declare no conflict of interest.



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2. Ai XY, Qin Y, Liu HJ, Cui ZH, Li M, Yang JH, et al. Apigenin inhibits colonic inflammation and tumorigenesis by suppressing STAT3-NF-κB signaling. Oncotarget. 2017;8:100216–26.
3. Amiri M, Nourian A, Khoshkam M, Ramazani A. Apigenin inhibits growth of the Plasmodium berghei and disrupts some metabolic pathways in mice. Phytother Res. 2018;32:1795–802.
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16. Hassan SM, Khalaf MM, Sadek SA, Abo-Youssef AM. Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. Pharm Biol. 2017;55:766–74.
17. He Y, Fang X, Shi J, Li X, Xie M, Liu X. Apigenin attenuates pulmonary hypertension by inducing mitochondria-dependent apoptosis of PASMCs via inhibiting the hypoxia inducible factor 1α-KV1.5 channel pathway. Chem Biol Interact. 2020;317:108942.
18. Herrmann KM. The shikimate pathway as an entry to aromatic secondary metabolism. Plant Physiol. 1995;107:7–12.
19. Huang S, Yu M, Shi N, Zhou Y, Li F, Li X, et al. Apigenin and Abivertinib, a novel BTK inhibitor synergize to inhibit diffuse large B-cell lymphoma in vivo and vitro. J Cancer. 2020;11:2123–32.
20. Jiang PY, Zhu XJ, Zhang YN, Zhou FF, Yang XF. Protective effects of apigenin on LPS-induced endometritis via activating Nrf2 signaling pathway. Microb Pathog. 2018;123:139–43.
21. Jiao R, Chen H, Wan Q, Zhang X, Dai J, Li X, et al. Apigenin inhibits fibroblast proliferation and reduces epidural fibrosis by regulating Wnt3a/β-catenin signaling pathway. J Orthop Surg Res. 2019;14:258.
22. Jing Y, Chen R, Dong M, Liu Y, Hou X, Guo P, et al. Apigenin relaxes rat intrarenal arteries, depresses Ca(2+)-activated Cl(-) currents and augments voltage-dependent K(+) currents of the arterial smooth muscle cells. Biomed Pharmacother. 2019;115:108926.
23. Kang CH, Molagoda IMN, Choi YH, Park C, Moon DO, Kim GY. Apigenin promotes TRAIL-mediated apoptosis regardless of ROS generation. Food Chem Toxicol. 2018;111:623–30.
24. Ketkaew Y, Osathanon T, Pavasant P, Sooampon S. Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck squamous cell carcinoma cell line. Arch Oral Biol. 2017;74:69–74.
25. Kowalczyk A, Bodalska A, Miranowicz M, Karłowicz-Bodalska K. Insights into novel anticancer applications for apigenin. Adv Clin Exp Med. 2017;26:1143–6.
26. Lee HH, Jung J, Moon A, Kang H, Cho H. Antitumor and anti-invasive effect of apigenin on human breast carcinoma through suppression of IL-6 expression. Int J Mol Sci. 2019;20:E3143.
27. Li D, Ma J, Wang L, Xin S. Spigenin prevent abdominal aortic aneurysms formation by inhibiting the NF-κB signaling pathway. J Cardiovasc Pharmacol. 2020;75:229–39.
28. Li G, Chi CW, Shao XF, Fang CH. Application of molecular imaging technology in evaluating the inhibiting effect of apigenin in vivo on subcutaneous hepatocellular carcinoma. Biochem Biophys Res Commun. 2017;487:122–7.
29. Li Y, Yang B, Bai JY, Xia S, Mao M, Li X, et al. The roles of synovial hyperplasia, angiogenesis and osteoclastogenesis in the protective effect of apigenin on collagen-induced arthritis. Int Immunopharmacol. 2019;73:362–9.
30. Liu Y, Li Z, Xue X, Wang Y, Zhang Y, Wang J. Apigenin reverses lung injury and immunotoxicity in paraquat-treated mice. Int Immunopharmacol. 2018;65:531–8.
31. Lu J, Meng Z, Cheng B, Liu M, Tao S, Guan S. Apigenin reduces the excessive accumulation of lipids induced by palmitic acid via the AMPK signaling pathway in HepG2 cells. Exp Ther Med. 2019;18:2965–71.
32. Malik S, Suchal K, Khan SI, Bhatia J, Kishore K, Dinda AK, et al. Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways. Am J Physiol Renal Physiol. 2017;313:F414–22.
33. Mirzoeva S, Tong X, Bridgeman BB, Plebanek MP, Volpert OV. Apigenin inhibits UVB-induced skin carcinogenesis: The role of thrombospondin-1 as an anti-inflammatory factor. Neoplasia. 2018;20:930–42.
34. Mrazek AA, Bhatia V, Falzon M, Spratt H, Chao C, Hellmich MR. Apigenin decreases acinar cell damage in pancreatitis. Pancreas. 2019;48:711–8.
35. Nabavi SF, Khan H, D'onofrio G, Šamec D, Shirooie S, Dehpour AR, et al. Apigenin as neuroprotective agent: Of mice and men. Pharmacol Res. 2018;128:359–65.
36. Nelson N, Szekeres K, Iclozan C, Rivera IO, McGill A, Johnson G, et al. Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer. PLoS One. 2017;12:e0170197.
37. Pang L, Zou S, Shi Y, Mao Q, Chen Y. Apigenin attenuates PM2.5-induced airway hyperresponsiveness and inflammation by down-regulating NF-κB in murine model of asthma. Int J Clin Exp Pathol. 2019;12:3700-9.
38. Qiu JG, Wang L, Liu WJ, Wang JF, Zhao EJ, Zhou FM, et al. Apigenin inhibits IL-6 transcription and suppresses esophageal carcinogenesis. Front Pharmacol. 2019;10:1002.
39. Quan W, Ma S, Zhu Y, Shao Q, Hou J, Li X. Apigenin-7-O-β-d-(6″-p-coumaroyl)-glucopyranoside reduces myocardial ischaemia/reperfusion injury in an experimental model via regulating the inflammation response. Pharm Biol. 2020;58:80–8.
40. Rašković A, Gigov S, Čapo I, Paut Kusturica M, Milijašević B, Kojić-Damjanov S, et al. Antioxidative and protective actions of apigenin in a paracetamol-induced hepatotoxicity rat model. Eur J Drug Metab Pharmacokinet. 2017;42:849–56.
41. Ren K, Jiang T, Zhou HF, Liang Y, Zhao GJ. Apigenin retards atherogenesis by promoting ABCA1-mediated cholesterol efflux and suppressing inflammation. Cell Physiol Biochem. 2018;47:2170–84.
42. Safari M, Parsaie H, Sameni HR, Aldaghi MR, Zarbakhsh S. Anti-oxidative and anti-apoptotic effects of apigenin on number of viable and apoptotic blastomeres, zona pellucida thickness and hatching rate of mouse embryos. Int J Fertil Steril. 2018;12:257–62.
43. Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The therapeutic potential of apigenin. Int J Mol Sci. 2019;20:E1305.
44. Sánchez-Marzo N, Pérez-Sánchez A, Ruiz-Torres V, Martínez-Tébar A, Castillo J, Herranz-López M, et al. Antioxidant and photoprotective activity of apigenin and its potassium salt derivative in human keratinocytes and absorption in caco-2 cell monolayers. Int J Mol Sci. 2019;20:2148.
45. Sang Y, Zhang F, Wang H, Yao J, Chen R, Zhou Z, et al. Apigenin exhibits protective effects in a mouse model of d-galactose-induced aging via activating the Nrf2 pathway. Food Funct. 2017;8:2331–40.
46. Shankar E, Goel A, Gupta K, Gupta S. Plant flavone apigenin: An emerging anticancer agent. Curr Pharmacol Rep. 2017;3:423–46.
47. Sharma A, Ghani A, Sak K, Tuli HS, Sharma AK, Setzer WN, et al. Probing into therapeutic anti-cancer potential of apigenin: Recent trends and future directions. Recent Pat Inflamm Allergy Drug Discov. 2019;13:124-33.
48. 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. 2018;30:1–10.
49. Siddique YH, Jyoti S. Alteration in biochemical parameters in the brain of transgenic Drosophila melanogaster model of Parkinson's disease exposed to apigenin. Integr Med Res. 2017;6:245–53.
50. Stump TA, Santee BN, Williams LP, Kunze RA, Heinze CE, Huseman ED, et al. The antiproliferative and apoptotic effects of apigenin on glioblastoma cells. J Pharm Pharmacol. 2017;69:907–16.
51. Tang D, Chen K, Huang L, Li J. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert Opin Drug Metab Toxicol. 2017;13:323–30.
52. Thangaiyan R, Robert BM, Arjunan S, Govindasamy K, Nagarajan RP. Preventive effect of apigenin against isoproterenol-induced apoptosis in cardiomyoblasts. J Biochem Mol Toxicol. 2018;32:e22213.
53. Tong J, Shen Y, Zhang Z, Hu Y, Zhang X, Han L. Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway. Biosci Rep. 2019;39:BSR20190452.
54. Wang F, Liu JC, Zhou RJ, Zhao X, Liu M, Ye H, et al. Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression. Chem Biol Interact. 2017;275:171–7.
55. Wang H, Guo B, Lin S, Chang P, Tao K. Apigenin inhibits growth and migration of fibroblasts by suppressing FAK signaling. Aging. 2019;11:3668–78.
56. Wang X, Wang W, Wang JZ, Yang C, Liang CZ. Effect of apigenin on apoptosis induced by renal ischemia/reperfusion injury in vivo and in vitro. Ren Fail. 2018;40:498–505.
57. Wu CC, Fang CY, Cheng YJ, Hsu HY, Chou SP, Huang SY, et al. Inhibition of epstein-barr virus reactivation by the flavonoid apigenin. J Biomed Sci. 2017;24:2.
58. Xu L, Zhang Y, Tian K, Chen X, Zhang R, Mu X, et al. Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects. J Exp Clin Cancer Res. 2018;37:261.
59. Zare MFR, Rakhshan K, Aboutaleb N, Nikbakht F, Naderi N, Bakhshesh M, et al. Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats. Life Sci. 2019;4:116623.
60. Zhang E, Zhang Y, Fan Z, Cheng L, Han S, Che H. Apigenin inhibits histamine-induced cervical cancer tumor growth by regulating estrogen receptor expression. Molecules. 2020;25:E1960.
61. Zhang K, Song W, Li D, Jin X. Apigenin in the regulation of cholesterol metabolism and protection of blood vessels. Exp Ther Med. 2017;13:1719–24.
62. Zhang X, Bu H, Jiang Y, Sun G, Jiang R, Huang X, et al. The antidepressant effects of apigenin are associated with the promotion of autophagy via the mTOR/ AMPK/ULK1 pathway. Mol Med Rep. 2019;20:2867–74.
63. Zhang Y, Sun Q, Li X, Ma X, Li Y, Jiao Z, et al. Apigenin suppresses mouse peritoneal fibrosis by down-regulating miR34a expression. Biomed Pharmacother. 2018;106:373–80.
64. Zhao F, Dang Y, Zhang R, Jing G, Liang W, Xie L, et al. Apigenin attenuates acrylonitrile-induced neuro-inflammation in rats: Involved of inactivation of the TLR4/NF-κB signaling pathway. Int Immunopharmacol. 2019;75:105697.
65. Zhong Y, Jin C, Gan J, Wang X, Shi Z, Xia X, et al. Apigenin attenuates patulin-induced apoptosis in HEK293 cells by modulating ROS-mediated mitochondrial dysfunction and caspase signal pathway. Toxicon. 2017;137:106–13.
66. Zhong Y, Jin C, Wang X, Li X, Han J, Xue W, et al. Protective effects of apigenin against 3-MCPD-induced renal injury in rat. Chem Biol Interact. 2018;296:9–17.
67. Zhou Q, Cheng KW, Gong J, Li ETS, Wang M. Apigenin and its methylglyoxal-adduct inhibit advanced glycation end products-induced oxidative stress and inflammation in endothelial cells. Biochem Pharmacol. 2019;166:231–41.

Table 1: Recent studies of the biological and pharmacological activities of apigenin

[*] Corresponding Author:

Sang Un Park, Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea; Tel.: +82-42-821-5730, Fax: +82-42-822-2631, eMail: supark@cnu.ac.kr