Research progress on icariin, a traditional Chinese medicine extract, in the treatment of asthma

Main Article Content

Jia-ying Yuan
Zhi-ying Tong
Yu-chao Dong
Jia-yi Zhao
Yan Shang


asthma, airway inflammation, airway remodeling, Chinese herbal extracts, Icariin


Bronchial asthma is a common chronic airway disease, and long-term management of asthma is the focus and challenge of clinical treatment. Glucocorticoids are often used as the first choice for the treatment of asthma. However, the occurrence of hormone dependence, hormone resistance, and local and systemic adverse reactions caused by hormone application also creates problems for the treatment of asthma. Finding new, safe, and effective therapeutic drugs is an important research direction at present. Icariin is an effective ingredient of the traditional Chinese medicine, Epimedium. It has various biological attributes such as anti-inflammatory and antioxidative activities, and immune regulation. It has high safety and a wide range of clinical applications. Icariin has the characteristics of multitargeted intervention in the treatment of asthma. Here, we review the specific mechanisms of icariin in treating asthma, and icariin is considered a novel therapy in controlling asthma; however, the mechanism is still worth further investigation.

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1. Tyler SR, Bunyavanich S. Leveraging-omics for asthma endotyping. J Allergy Clin Immunol. 2019 Jul;144(1):13–23. 10.1016/j.jaci.2019.05.015

2. Prabhala P, Wright DB, Robbe P, Bitter C, Pera T, Ten Hacken NHT, et al. Laminin α4 contributes to airway remodeling and inflammation in asthma. Am J Physiol Lung Cell Mol Physiol. 2019 Dec 1;317(6):L768–L777. 10.1152/ajplung.00222.2019

3. Stokes JR, Casale TB. Characterization of asthma endotypes: implications for therapy. Ann Allergy Asthma Immunol. 2016 Aug;117(2):121–125. 10.1016/j.anai.2016.05.016

4. Casale TB. Biologics and biomarkers for asthma, urticaria, and nasal polyposis. J Allergy Clin Immunol. 2017 May;139(5):1411–1421. 10.1016/j.jaci.2017.03.006

5. Ramakrishnan RK, Al Heialy S, Hamid Q. Role of IL-17 in asthma pathogenesis and its implications for the clinic. Expert Rev Respir Med. 2019 Nov;13(11):1057–1068. 10.1080/17476348.2019.1666002

6. Wang AL, Panganiban R, Qiu W, Kho AT, Chupp G, Meyers DA, et al. Drug repurposing to treat glucocorticoid resistance in asthma. J Pers Med. 2021 Mar 3;11(3):175. 10.3390/jpm11030175

7. Wang Y, Chen YJ, Xiang C, Jiang GW, Xu YD, Yin LM, et al. Discovery of potential asthma targets based on the clinical efficacy of traditional Chinese medicine formulas. J Ethnopharmacol. 2020 Apr 24; 252:112635. 10.1016/j.jep.2020.112635

8. Ma H, He X, Yang Y, Li M, Hao D, Jia Z. The genus Epimedium: an ethnopharmacological and phytochemical review. J Ethnopharmacol. 2011 Apr 12;134(3):519–541. 10.1016/j.jep.2011.01.001

9. Chen M, Wu J, Luo Q, Mo S, Lyu Y, Wei Y, et al. The anticancer properties of Herba Epimedii and its main bioactive Componentsicariin and Icariside II. Nutrients. 2016 Sep 13;8(9):563. 10.3390/nu8090563

10. Zhao JF, Xu JY, Xu YE, Chen SL, Guo YX, Gao QY, et al. High-throughput metabolomics method for discovering metabolic biomarkers and pathways to reveal effects and molecular mechanism of ethanol extract from Epimedium against osteoporosis. Front Pharmacol. 2020 Aug 27;11:1318. 10.3389/fphar.2020.01318

11. Huang W, Song Y, Wang L. Wenshen decoction suppresses inflammation in IL-33-induced asthma murine model via inhibiting ILC2 activation. Ann Transl Med. 2019 Oct;7(20):570. 10.21037/atm.2019.09.34

12. Kim JY, Shim SH. Epimedium koreanum extract and its flavonoids reduced atherosclerotic risk via suppressing modification of human HDL. Nutrients. 2019 May 18;11(5):1110. 10.3390/nu11051110

13. Jiang J, Jie S, Jia XB. Phytochemistry and ethnopharmacology of Epimedium L. species. Chinese Herbal Med. 2015;7(3):204–222. 10.1016/S1674-6384(15)60043-0

14. Cao LH, Qiao JY, Huang HY, Fang XY, Zhang R, Miao MS, et al. PI3K–AKT signaling activation and icariin: the potential effects on the perimenopausal depression-like rat model. Molecules. 2019 Oct 15;24(20):3700. 10.3390/molecules24203700

15. Chen S, Wang Z, Zhou H, He B, Hu D, Jiang H. Icariin reduces high glucose-induced endothelial progenitor cell dysfunction via inhibiting the p38/CREB pathway and activating the Akt/eNOS/NO pathway. Exp Ther Med. 2019 Dec;18(6):4774–4780. 10.3892/etm.2019.8132

16. Wang M, Gao H, Li W, Wu B. Icariin and its metabolites regulate lipid metabolism: from effects to molecular mechanisms. Biomed Pharmacother. 2020 Nov; 131:110675. 10.1016/j.biopha.2020.110675

17. Xiao H, Wignall N, Brown ES. An open-label pilot study of icariin for co-morbid bipolar and alcohol use disorder. Am J Drug Alcohol Abuse. 2016;42(2):162–167. 10.3109/00952990.2015.1114118

18. Wu X, Kong W, Qi X, Wang S, Chen Y, Zhao Z, et al. Icariin induces apoptosis of human lung adenocarcinoma cells by activating the mitochondrial apoptotic pathway. Life Sci. 2019 Dec 15; 239:116879. 10.1016/j.lfs.2019.116879

19. Qi C, Shao Y, Liu X, Wang D, Li X. The cardioprotective effects of icariin on the isoprenaline-induced takotsubo-like rat model: involvement of reactive oxygen species and the TLR4/NF-κB signaling pathway. Int Immunopharmacol. 2019 Sep;74:105733. 10.1016/j.intimp.2019.105733

20. Xie Y, Sun W, Yan F, Liu H, Deng Z, Cai L. Icariin-loaded porous scaffolds for bone regeneration through the regulation of the coupling process of osteogenesis and osteoclastic activity. Int J Nanomedicine. 2019 Aug 1;14:6019–6033. 10.2147/IJN.S203859

21. Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res. 2018 Jun 8;19(1):113. 10.1186/s12931-018-0813-0

22. Pal K, Feng X, Steinke JW, Burdick MD, Shim YM, Sung SS, et al. Leukotriene A4 hydrolase activation and leukotriene B4 production by eosinophils in severe asthma. Am J Respir Cell Mol Biol. 2019 Apr;60(4):413–419. 10.1165/rcmb.2018-0175OC

23. Kabashima K, Nakashima C, Nonomura Y, Otsuka A, Cardamone C, Parente R, et al. Biomarkers for evaluation of mast cell and basophil activation. Immunol Rev. 2018 Mar;282(1):114–120. 10.1111/imr.12639

24. Wang J, Wu J, Kong L, Nurahmat M, Chen M, Luo Q, et al. BuShenYiQi formula strengthens Th1 response and suppresses Th2-Th17 responses in RSV-induced asthma exacerbated mice. J Ethnopharmacol. 2014 May 28;154(1):131–147. 10.1016/j.jep.2014.03.041

25. Wei Y, Luo QL, Sun J, Chen MX, Liu F, Dong JC. Bu-Shen-Yi-Qi formulae suppress chronic airway inflammation and regulate Th17/Treg imbalance in the murine ovalbumin asthma model. J Ethnopharmacol. 2015 Apr 22;164:368–377. 10.1016/j.jep.2015.01.016

26. Du WJ, Dong JC, Cai C. [Effects of icariin on Bcl-2 and Bax protein expressions and eosinophils apoptosis in bronchial asthmatic mice]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2011 Sep;31(9):1248–1253. Chinese.

27. Bošnjak B, Kazemi S, Altenburger LM, Mokrović G, Epstein MM. Th2-T RMs maintain life-long allergic memory in experimental asthma in mice. Front Immunol. 2019 Apr 24;10:840. 10.3389/fimmu.2019.00840

28. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012 May 4;18(5):673–683. 10.1038/nm.2731

29. Pang L, Yu P, Liu X, Fan Y, Shi Y, Zou S. Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice. Mol Med Rep. 2021 May;23(5):378. 10.3892/mmr.2021.12017

30. Rhew KY, Han Y. Immunoadjuvant activity of icariin that induces Th1-type antibody in mice. Arch Pharm Res. 2012 Sep;35(9):1685–1691. 10.1007/s12272-012-0920-2

31. Xu CQ, LE JJ, Duan XH, DU WJ, Liu BJ, Wu JF, et al. Molecular mechanism of icariin on rat asthmatic model. Chin Med J (Engl). 2011 Sep;124(18):2899–2906.

32. Chen Q, Guo X, Deng N, Liu L, Chen S, Wang A, et al. α-Galactosylceramide treatment before allergen sensitization promotes iNKT cell-mediated induction of Treg cells, preventing Th2 cell responses in murine asthma. J Biol Chem. 2019 Apr 5;294(14):5438–5455. 10.1074/jbc.RA118.005418

33. Jing W, Wang W, Liu Q. Passive smoking induces pediatric asthma by affecting the balance of Treg/Th17 cells. Pediatr Res. 2019 Mar;85(4):469–476. 10.1038/s41390-019-0276-0

34. Wei Y, Liu B, Sun J, Lv Y, Luo Q, Liu F, et al. Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model. Immunobiology. 2015 Jun;220(6):789–797. 10.1016/j.imbio.2014.12.015

35. Bing J, Li YY, Yang WJ, Zhang LZ, Fang M S, Fu HY, et al. Jinkui Shenqi pills ameliorate asthma with “kidney yang deficiency” by enhancing the function of the hypothalamic-pituitary-adrenal axis to regulate T helper 1/2 imbalance. Evid Based Complement Alternat Med. 2018 Feb 8;2018:7253240. 10.1155/2018/7253240

36. Kim SH, Kim DH, Lavender P, Seo JH, Kim YS, Park JS, et al. Repression of TNF-alpha-induced IL-8 expression by the glucocorticoid receptor-beta involves inhibition of histone H4 acetylation. Exp Mol Med. 2009 May 31;41(5):297–306. 10.3858/emm.2009.41.5.033

37. He Y, Shi J, Nguyen QT, You E, Liu H, Ren X, et al. Development of highly potent glucocorticoids for steroid-resistant severe asthma. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):6932–6937. 10.1073/pnas.1816734116

38. Kong L, Liang X, Liu A, Yang X, Luo Q, Lv Y, et al. Icariin inhibits inflammation via immunomodulation of the cutaneous hypothalamus-pituitary-adrenal axis in vitro. Clin Exp Dermatol. 2019 Mar;44(2):144–152. 10.1111/ced.13735

39. Sun X, Deng X, Cai W, Li W, Shen Z, Jiang T, et al. Icariin inhibits LPS-induced cell inflammatory response by promoting GRα nuclear translocation and upregulating GRα expression. Life Sci. 2018 Feb 15;195:33–43. 10.1016/j.lfs.2018.01.006

40. Tang X, Nian H, Li X, Yang Y, Wang X, Xu L, et al. Effects of the combined extracts of Herba Epimedii and Fructus Ligustrilucidi on airway remodeling in the asthmatic rats with the treatment of budesonide. BMC Complement Altern Med. 2017 Aug 1;17(1):380. 10.1186/s12906-017-1891-0

41. Uchida Y, Soma T, Nakagome K, Kobayashi T, Nagata M. Implications of prostaglandin D2 and leukotrienes in exhaled breath condensates of asthma. Ann Allergy Asthma Immunol. 2019 Jul;123(1):81–88.e1. 10.1016/j.anai.2019.04.008

42. Johnsson AK, Choi JH, Rönnberg E, Fuchs D, Kolmert J, Hamberg M, et al. Selective inhibition of prostaglandin D biosynthesis in human mast cells to overcome need for multiple receptor antagonists: biochemical consequences. Clin Exp Allergy. 2021 Apr;51(4):594–603. 10.1111/cea.13831

43. Qiao J, Sun S, Yuan L, Wang J. Effects of icariin on asthma mouse model are associated with regulation of prostaglandin D2 level. Allergol Immunopathol (Madr). 2017 Nov–Dec;45(6):567–572. 10.1016/j.aller.2017.02.007

44. Qin W, Wu X, Jia Y, Tong X, Guo C, Chen D, et al. Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma. Biomed Pharmacother. 2019 Oct;118:109188. 10.1016/j.biopha.2019.109188

45. Kim HK, Lee GH, Bhattarai KR, Junjappa RP, Lee HY, Handigund M, et al. PI3Kδ contributes to ER stress-associated asthma through ER-redox disturbances: the involvement of the RIDD-RIG-I-NF-κB axis. Exp Mol Med. 2018 Feb 16;50(2):e444. 10.1038/emm.2017.270

46. Liu J, Liu L, Sun J, Luo Q, Yan C, Zhang H, et al. Icariin protects hippocampal neurons from endoplasmic reticulum stress and NF-κB mediated apoptosis in fetal rat hippocampal neurons and asthma rats. Front Pharmacol. 2020 Jan 31;10:1660. 10.3389/fphar.2019.01660

47. Vieira CP, de Oliveira LP, Da Silva MB, Majolli Andre D, Tavares EBG, Pimentel ER, et al. Role of metalloproteinases and TNF-α in obesity-associated asthma in mice. Life Sci. 2020 Oct 15;259:118191. 10.1016/j.lfs.2020.118191

48. Yao Z, Fu Y. Glycyrrhizic acid restrains airway inflammation and remodeling in asthma via the TGF-β1/Smad signaling pathway. Exp Ther Med. 2021 May;21(5):461. 10.3892/etm.2021.9892

49. Wang K, Zheng X, Pan Z, Yao W, Gao X, Wang X, et al. Icariin prevents extracellular matrix accumulation and ameliorates experimental diabetic kidney disease by inhibiting oxidative stress via GPER mediated p62-dependent Keap1 degradation and Nrf2 activation. Front Cell Dev Biol. 2020 Jul 17;8:559. 10.3389/fcell.2020.00559

50. Song Y, Wang Z, Jiang J, Piao Y, Li L, Xu C, et al. DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodeling by suppressing TGF-β1/Smad, MAPK and PI3K signaling pathway in asthma. J Cell Mol Med. 2020 Dec;24(23):13739–13750. 10.1111/jcmm.15942

51. Sun Z, Ji N, Ma Q, Zhu R, Chen Z, Wang Z, et al. Epithelial-mesenchymal transition in asthma airway remodeling is regulated by the IL-33/CD146 axis. Front Immunol. 2020 Jul 22;11:1598. 10.3389/fimmu.2020.01598

52. Fan Q, Jian Y. MiR-203a-3p regulates TGF-β1-induced epithelial-mesenchymal transition (EMT) in asthma by regulating Smad3 pathway through SIX1. Biosci Rep. 2020 Feb 28;40(2):BSR20192645. 10.1042/BSR20192645

53. Li Z, Yuan X, Wang B, Gao F. Icariin alleviates transforming growth factor-β1-induced epithelial-mesenchymal transition by targeting Smad and MAPK signaling pathways. Am J Transl Res. 2020 Feb 15;12(2):343–360. eCollection 2020.

54. Dilasser F, Rose L, Hassoun D, Klein M, Rousselle M, Brosseau C, et al. Essential role of smooth muscle Rac1 in severe asthma-associated airway remodeling. Thorax. 2021 Feb 4;76(4):326–334. 10.1136/thoraxjnl-2020-216271

55. Yang L, Xiao B, Hou L, Zhou G, Mo B, Yao D. Bioactive molecule Icariin inhibited proliferation while enhanced apoptosis and autophagy of rat airway smooth muscle cells in vitro. Cytotechnology. 2019 Dec;71(6):1109–1120. 10.1007/s10616-019-00348-9

56. Hu L, Li L, Zhang H, Li Q, Jiang S, Qiu J, et al. Inhibition of airway remodeling and inflammatory response by Icariin in asthma. BMC Complement Altern Med. 2019 Nov 19;19(1):316. 10.1186/s12906-019-2743-x

57. Li R, Wang F, Wei J, Lin Y, Tang G, Rao L, et al. The role of macrophage migration inhibitory factor (MIF) in asthmatic airway remodeling. Allergy Asthma Immunol Res. 2021 Jan;13(1):88–105. 10.4168/aair.2021.13.1.88

58. Yang H, Yan L, Qian P, Duan H, Wu J, Li B, et al. Icariin inhibits foam cell formation by down-regulating the expression of CD36 and up-regulating the expression of SR-BI. J Cell Biochem. 2015 Apr;116(4):580–588. 10.1002/jcb.25009

59. Saradna A, Do DC, Kumar S, Fu QL, Gao P. Macrophage polarization and allergic asthma. Transl Res. 2018 Jan;191:1–14. 10.1016/j.trsl.2017.09.002

60. Teo YL, Cheong WF, Cazenave-Gassiot A, Ji S, Logan S, Lee ZXK, et al. Pharmacokinetics of prenylflavonoids following oral ingestion of standardized epimedium extract in humans. Planta Med. 2019 Mar;85(4):347–355. 10.1055/a-0806-7673

61. Zhang G, Qin L, Shi Y. Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res. 2007 Jul;22(7):1072–1079. 10.1359/jbmr.070405

62. Li M, Zheng W, Zhang C, Yan Q, Peng Z, Xie F, et al. Chuankezhi injection for asthma: protocol of a systematic review and meta-analysis. Medicine (Baltimore). 2019 Aug;98(33):e16630. 10.1097/MD.0000000000016630