Abstract
Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the “best hope for the treatment of malaria” by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the “artemisinin story” and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.
Keywords: artemisinin, drug repurposing, cancer, inflammation, COVID-19, traditional Chinese medicine
Acknowledgements
The authors gratefully acknowledge the financial support from the National Key R&D Program of China (No. 2020YFA0908000), the National Natural Science Foundation of China (Nos. 82074098 and 82104480), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-C-202002), the CACMS Innovation Fund (No. CI2021A05101), and the Fundamental Research Funds for the Central Public Welfare Research Institutes (Nos. ZZ14-YQ-050, ZZ14-YQ-051, ZZ14-YQ-059, ZZ14-YQ-060, ZZ14-ND-010, ZZ14-LFL-002, ZZ15-ND-10, ZXKT19018, and ZXKT19021).
Footnotes
Compliance with ethics guidelines
Qiaoli Shi, Fei Xia, Qixin Wang, Fulong Liao, Qiuyan Guo, Chengchao Xu, and Jigang Wang declare that they have no conflict of interest. This manuscript is a review article, and it does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.
Contributor Information
Qiuyan Guo, Email: qyguo@icmm.ac.cn.
Chengchao Xu, Email: ccxu@icmm.ac.cn.
Jigang Wang, Email: jgwang@icmm.ac.cn.
References
- 1.Tu YY. Artemisinin—a gift from traditional Chinese medicine to the world (Nobel Lecture) Angew Chem Int Ed Eng. 2016;155(35):10210–10226. doi: 10.1002/anie.201601967. [DOI] [PubMed] [Google Scholar]
- 2.World Health Organization . World malaria report 2020: 20 years of global progress and challenges. Geneva: World Health Organization; 2020. [Google Scholar]
- 3.Yoshida GJ. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. J Hematol Oncol. 2017;10(1):67. doi: 10.1186/s13045-017-0436-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Efferth T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017;46:65–83. doi: 10.1016/j.semcancer.2017.02.009. [DOI] [PubMed] [Google Scholar]
- 5.Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014;142(1):126–139. doi: 10.1016/j.pharmthera.2013.12.001. [DOI] [PubMed] [Google Scholar]
- 6.Li G, Yuan M, Li H, Deng C, Wang Q, Tang Y, Zhang H, Yu W, Xu Q, Zou Y, Yuan Y, Guo J, Jin C, Guan X, Xie F, Song J. Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: an open-label, non-randomised and controlled trial. Int J Antimicrob Agents. 2021;57(1):106216. doi: 10.1016/j.ijantimicag.2020.106216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Gendrot M, Duflot I, Boxberger M, Delandre O, Jardot P, Le Bideau M, Andreani J, Fonta I, Mosnier J, Rolland C, Hutter S, La Scola B, Pradines B. Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: in vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate. Int J Infect Dis. 2020;99:437–440. doi: 10.1016/j.ijid.2020.08.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, Kamarulzaman A, Sall A, Kremsner P. Repurposing antimalarials to tackle the COVID-19 pandemic. Trends Parasitol. 2021;37(1):8–11. doi: 10.1016/j.pt.2020.10.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Yang J, He Y, Li Y, Zhang X, Wong YK, Shen S, Zhong T, Zhang J, Liu Q, Wang J. Advances in the research on the targets of antimalaria actions of artemisinin. Pharmacol Ther. 2020;216:107697. doi: 10.1016/j.pharmthera.2020.107697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wang J, Xu C, Liao FL, Jiang T, Krishna S, Tu Y. Suboptimal dosing triggers artemisinin partner drug resistance. Lancet Infect Dis. 2019;19(11):1167–1168. doi: 10.1016/S1473-3099(19)30535-3. [DOI] [PubMed] [Google Scholar]
- 11.Wang J, Xu C, Liao FL, Jiang T, Krishna S, Tu Y. A temporizing solution to “artemisinin resistance”. N Engl J Med. 2019;380(22):2087–2089. doi: 10.1056/NEJMp1901233. [DOI] [PubMed] [Google Scholar]
- 12.Strategic Advisory Group on Malaria Eradication . Malaria eradication: benefits, future scenarios and feasibility. A report of the Strategic Advisory Group on Malaria Eradication. Geneva: World Health Organization; 2020. [Google Scholar]
- 13.Ma N, Zhang Z, Liao F, Jiang T, Tu Y. The birth of artemisinin. Pharmacol Ther. 2020;216:107658. doi: 10.1016/j.pharmthera.2020.107658. [DOI] [PubMed] [Google Scholar]
- 14.Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011;17(10):1217–1220. doi: 10.1038/nm.2471. [DOI] [PubMed] [Google Scholar]
- 15.World Health Organization . Guidelines for the treatment of malaria. 1st ed. Geneva: World Health Organization; 2006. [Google Scholar]
- 16.Efferth T, Kaina B. Toxicity of the antimalarial artemisinin and its dervatives. Crit Rev Toxicol. 2010;40(5):405–421. doi: 10.3109/10408441003610571. [DOI] [PubMed] [Google Scholar]
- 17.The Nobel Prize. The Nobel Prize in Physiology or Medicine. 2015. https://www.nobelprize.org/priees/medicine/2015ssummary/ (accessed March 5, 2021)
- 18.World Health Organization . World Health Organization Model List of Essential Medicines. Geneva: World Health Organization; 2019. [Google Scholar]
- 19.Eastman RT, Fidock DA. Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat Rev Microbiol. 2009;7(12):864–874. doi: 10.1038/nrmicro2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Sun X, Yan P, Zou C, Wong YK, Shu Y, Lee YM, Zhang C, Yang ND, Wang J, Zhang J. Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives. Med Res Rev. 2019;39(6):2172–2193. doi: 10.1002/med.21580. [DOI] [PubMed] [Google Scholar]
- 21.Woerdenbag HJ, Moskal TA, Pras N, Malingré TM, el-Feraly FS, Kampinga HH, Konings AW. Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod. 1993;56(6):849–856. doi: 10.1021/np50096a007. [DOI] [PubMed] [Google Scholar]
- 22.Lai HC, Singh NP, Sasaki T. Development of artemisinin compounds for cancer treatment. Invest New Drugs. 2013;31(1):230–246. doi: 10.1007/s10637-012-9873-z. [DOI] [PubMed] [Google Scholar]
- 23.King D, Yeomanson D, Bryant HE. PI3King the lock: targeting the PI3K/Akt/mTOR pathway as a novel therapeutic strategy in neuroblastoma. J Pediatr Hematol Oncol. 2015;37(4):245–251. doi: 10.1097/MPH.0000000000000329. [DOI] [PubMed] [Google Scholar]
- 24.Wang J, Zhang J, Shi Y, Xu C, Zhang C, Wong YK, Lee YM, Krishna S, He Y, Lim TK, Sim W, Hua ZC, Shen HM, Lin Q. Mechanistic investigation of the specific anticancer property of artemisinin and its combination with aminolevulinic acid for enhanced anticolorectal cancer activity. ACS Cent Sci. 2017;3(7):743–750. doi: 10.1021/acscentsci.7b00156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Yang ND, Tan SH, Ng S, Shi Y, Zhou J, Tan KSW, Wong WSF, Shen HM. Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin. J Biol Chem. 2014;289(48):33425–33441. doi: 10.1074/jbc.M114.564567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Feng FB, Qiu HY. Effects of artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis. Biomed Pharmacother. 2018;102:1209–1220. doi: 10.1016/j.biopha.2018.03.142. [DOI] [PubMed] [Google Scholar]
- 27.Wang YS, Yu P, Wang Y, Zhang J, Hang W, Yin ZX, Liu G, Chen J, Werle KD, Quan CS, Gao H, Zeng Q, Cui R, Liang J, Ding Q, Li YL, Xu ZX. AMP-activated protein kinase protects against necroptosis via regulation of Keap1-PGAM5 complex. Int J Cardiol. 2018;259:153–162. doi: 10.1016/j.ijcard.2018.01.036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Carling D. AMPK signalling in health and disease. Curr Opin Cell Biol. 2017;45:31–37. doi: 10.1016/j.ceb.2017.01.005. [DOI] [PubMed] [Google Scholar]
- 29.Choi YK, Park KG. Metabolic roles of AMPK and metformin in cancer cells. Mol Cells. 2013;36(4):279–287. doi: 10.1007/s10059-013-0169-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Du J, Wang T, Li Y, Zhou Y, Wang X, Yu X, Ren X, An Y, Wu Y, Sun W, Fan W, Zhu Q, Wang Y, Tong X. DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. Free Radic Biol Med. 2019;131:356–369. doi: 10.1016/j.freeradbiomed.2018.12.011. [DOI] [PubMed] [Google Scholar]
- 31.Zhou X, Chen Y, Wang F, Wu H, Zhang Y, Liu J, Cai Y, Huang S, He N, Hu Z, Jin X. Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. Chem Biol Interact. 2020;331:109273. doi: 10.1016/j.cbi.2020.109273. [DOI] [PubMed] [Google Scholar]
- 32.Cheng C, Wang T, Song Z, Peng L, Gao M, Hermine O, Rousseaux S, Khochbin S, Mi JQ, Wang J. Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044. Cancer Med. 2018;7(2):380–396. doi: 10.1002/cam4.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Orlova A, Wagner C, de Araujo ED, Bajusz D, Neubauer HA, Herling M, Gunning PT, Keserű GM, Moriggl R. Direct targeting options for STAT3 and STAT5 in cancer. Cancers (Basel) 2019;11(12):1930. doi: 10.3390/cancers11121930. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Yan X, Li P, Zhan Y, Qi M, Liu J, An Z, Yang W, Xiao H, Wu H, Qi Y, Shao H. Dihydroartemisinin suppresses STAT3 signaling and Mcl-1 and survivin expression to potentiate ABT-263-induced apoptosis in non-small cell lung cancer cells harboring EGFR or RAS mutation. Biochem Pharmacol. 2018;150:72–85. doi: 10.1016/j.bcp.2018.01.031. [DOI] [PubMed] [Google Scholar]
- 35.Wang W, Sun Y, Li X, Shi X, Li Z, Lu X. Dihydroartemisinin prevents distant metastasis of laryngeal carcinoma by inactivating STAT3 in cancer stem cells. Med Sci Monit. 2020;26:e922348. doi: 10.12659/MSM.922348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Ilamathi M, Prabu PC, Ayyappa KA, Sivaramakrishnan V. Artesunate obliterates experimental hepatocellular carcinoma in rats through suppression of IL-6-JAK-STAT signalling. Biomed Pharmacother. 2016;82:72–79. doi: 10.1016/j.biopha.2016.04.061. [DOI] [PubMed] [Google Scholar]
- 37.Berköz M, Özkan-Yilmaz F, Özlüer-Hunt A, Krośniak M, Türkmen Ö, Korkmaz D, Keskin S. Artesunate inhibits melanoma progression in vitro via suppressing STAT3 signaling pathway. Pharmacol Rep. 2021;73(2):650–663. doi: 10.1007/s43440-021-00230-6. [DOI] [PubMed] [Google Scholar]
- 38.Zheng L, Wang C, Luo T, Lu B, Ma H, Zhou Z, Zhu D, Chi G, Ge P, Luo Y. JNK activation contributes to oxidative stress-induced parthanatos in glioma cells via increase of intracellular ROS production. Mol Neurobiol. 2017;54(5):3492–3505. doi: 10.1007/s12035-016-9926-y. [DOI] [PubMed] [Google Scholar]
- 39.Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Cell Biol. 2007;19(2):142–149. doi: 10.1016/j.ceb.2007.02.001. [DOI] [PubMed] [Google Scholar]
- 40.Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006;26(24):9220–9231. doi: 10.1128/MCB.01453-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Wei Y, Sinha S, Levine B. Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation. Autophagy. 2008;4(7):949–951. doi: 10.4161/auto.6788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Yao GD, Ge MY, Li DQ, Chen L, Hayashi T, Tashiro SI, Onodera S, Guo C, Song SJ, Ikejima T. L-A03, a dihydroartemisinin derivative, promotes apoptotic cell death of human breast cancer MCF-7 cells by targeting c-Jun N-terminal kinase. Biomed Pharmacother. 2018;105:320–325. doi: 10.1016/j.biopha.2018.05.093. [DOI] [PubMed] [Google Scholar]
- 43.Orlowski RZ, Baldwin AS., Jr. NF-κB as a therapeutic target in cancer. Trends Mol Med. 2002;8(8):385–389. doi: 10.1016/S1471-4914(02)02375-4. [DOI] [PubMed] [Google Scholar]
- 44.Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB. J Clin Invest. 2001;107(3):241–246. doi: 10.1172/JCI11991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Chen X, Wong YK, Lim TK, Lim WH, Lin QS, Wang JG, Hua ZC. Artesunate activates the intrinsic apoptosis of HCT116 cells through the suppression of fatty acid synthesis and the NF-κB pathway. Molecules. 2017;22(8):1272. doi: 10.3390/molecules22081272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Hu W, Chen SS, Zhang JL, Lou XE, Zhou HJ. Dihydroartemisinin induces autophagy by suppressing NF-κB activation. Cancer Lett. 2014;343(2):239–248. doi: 10.1016/j.canlet.2013.09.035. [DOI] [PubMed] [Google Scholar]
- 47.Li B, Bu S, Sun J, Guo Y, Lai D. Artemisinin derivatives inhibit epithelial ovarian cancer cells via autophagy-mediated cell cycle arrest. Acta Biochim Biophys Sin (Shanghai) 2018;50(12):1227–1235. doi: 10.1093/abbs/gmy125. [DOI] [PubMed] [Google Scholar]
- 48.Lin Y, Jiang M, Chen W, Zhao T, Wei Y. Cancer and ER stress: mutual crosstalk between autophagy, oxidative stress and inflammatory response. Biomed Pharmacother. 2019;118:109249. doi: 10.1016/j.biopha.2019.109249. [DOI] [PubMed] [Google Scholar]
- 49.Xiao R, Ding C, Zhu H, Liu X, Gao J, Liu Q, Lu D, Zhang N, Zhang A, Zhou H. Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer. Cancer Lett. 2020;475:22–33. doi: 10.1016/j.canlet.2020.01.035. [DOI] [PubMed] [Google Scholar]
- 50.Våtsveen TK, Myhre MR, Steen CB, Wälchli S, Lingjærde OC, Bai B, Dillard P, Theodossiou TA, Holien T, Sundan A, Inderberg EM, Smeland EB, Myklebust JH, Oksvold MP. Artesunate shows potent anti-tumor activity in B-cell lymphoma. J Hematol Oncol. 2018;11(1):23. doi: 10.1186/s13045-018-0561-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Dai X, Zhang X, Chen W, Chen Y, Zhang Q, Mo S, Lu J. Dihydroartemisinin: a potential natural anticancer drug. Int J Biol Sci. 2021;17(2):603–622. doi: 10.7150/ijbs.50364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Shi C, Li H, Yang Y, Hou L. Anti-inflammatory and immuno-regulatory functions of artemisinin and its derivatives. Mediators Inflamm. 2015;2015:435713. doi: 10.1155/2015/435713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Zhou WL, Wu JM, Wu QL, Wang JX, Zhou Y, Zhou R, He PL, Li XY, Yang YF, Zhang Y, Li Y, Zuo JP. A novel artemisinin derivative, 3-(12-β-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo. Acta Pharmacol Sin. 2005;26(11):1352–1358. doi: 10.1111/j.1745-7254.2005.00232.x. [DOI] [PubMed] [Google Scholar]
- 54.Yang ZS, Wang JX, Zhou Y, Zuo JP, Li Y. Synthesis and immunosuppressive activity of new artemisinin derivatives. Part 2: 2-[12(β or α)-dihydroartemisinoxymethyl(or1′-ethyl)]phenoxyl propionic acids and esters. Bioorg Med Chem. 2006;14(23):8043–8049. doi: 10.1016/j.bmc.2006.07.038. [DOI] [PubMed] [Google Scholar]
- 55.Zhang JX, Wang JX, Zhang Y, Zuo JP, Wu JM, Sui Y, Li Y. Synthesis and immunosuppressive activity of new artemisinin derivatives containing polyethylene glycol group. Acta Pharmaceutica Sinica (Yao Xue Xue Bao) 2006;41(1):65–70. [PubMed] [Google Scholar]
- 56.Hou LF, He SJ, Wang JX, Yang Y, Zhu FH, Zhou Y, He PL, Zhang Y, Yang YF, Li Y, Tang W, Zuo JP. SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo. Int Immunopharmacol. 2009;9(13–14):1509–1517. doi: 10.1016/j.intimp.2009.09.003. [DOI] [PubMed] [Google Scholar]
- 57.Hou L, Block KE, Huang H. Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis. PLoS One. 2014;9(8):e104762. doi: 10.1371/journal.pone.0104762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58.He Y, Fan J, Lin H, Yang X, Ye Y, Liang L, Zhan Z, Dong X, Sun L, Xu H. The anti-malaria agent artesunate inhibits expression of vascular endothelial growth factor and hypoxia-inducible factor-1α in human rheumatoid arthritis fibroblast-like synoviocyte. Rheumatol Int. 2011;31(1):53–60. doi: 10.1007/s00296-009-1218-7. [DOI] [PubMed] [Google Scholar]
- 59.Hou LF, He SJ, Li X, Yang Y, He PL, Zhou Y, Zhu FH, Yang YF, Li Y, Tang W, Zuo JP. Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses. Arthritis Rheum. 2011;63(8):2445–2455. doi: 10.1002/art.30392. [DOI] [PubMed] [Google Scholar]
- 60.Li WD, Dong YJ, Tu YY, Lin ZB. Dihydroarteannuin ameliorates lupus symptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation. Int Immunopharmacol. 2006;6(8):1243–1250. doi: 10.1016/j.intimp.2006.03.004. [DOI] [PubMed] [Google Scholar]
- 61.Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine storm in COVID-19: the current evidence and treatment strategies. Front Immunol. 2020;11:1708. doi: 10.3389/fimmu.2020.01708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Gendrot M, Duflot I, Boxberger M, Delandre O, Jardot P, Le Bideau M, Andreani J, Fonta I, Mosnier J, Rolland C, Hutter S, La Scola B, Pradines B. Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: in vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate. Int J Infect Dis. 2020;99:437–440. doi: 10.1016/j.ijid.2020.08.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63.Li G, Yuan M, Li H, Deng C, Wang Q, Tang Y, Zhang H, Yu W, Xu Q, Zou Y, Yuan Y, Guo J, Jin C, Guan X, Xie F, Song J. Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: an open-label, non-randomised and controlled trial. Int J Antimicrob Agents. 2021;57(1):106216. doi: 10.1016/j.ijantimicag.2020.106216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64.Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, Kamarulzaman A, Sall A, Kremsner P. Repurposing antimalarials to tackle the COVID-19 pandemic. Trends Parasitol. 2021;37(1):8–11. doi: 10.1016/j.pt.2020.10.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 65.Chen K, Hua H, Zhu Z, Wu T, Jia Z, Liu Q. Artemisinin and dihydroartemisinin promote β-cell apoptosis induced by palmitate via enhancing ER stress. Apoptosis. 2020;25(3–4):192–204. doi: 10.1007/s10495-019-01587-z. [DOI] [PubMed] [Google Scholar]
- 66.Xue X, Dong Z, Deng Y, Yin S, Wang P, Liao Y, Hu G, Chen Y. Dihydroartemisinin alleviates atopic dermatitis in mice by inhibiting mast cell infiltration. J South Med Univ (Nan Fang Yi Ke Da Xue Xue Bao) 2020;40(10):1480–1487. doi: 10.12122/j.issn.1673-4254.2020.10.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67.Nong X, Rajbanshi G, Chen L, Li J, Li Z, Liu T, Chen S, Wei G, Li J. Effect of artesunate and relation with TGF-β1 and SMAD3 signaling on experimental hypertrophic scar model in rabbit ear. Arch Dermatol Res. 2019;311(10):761–772. doi: 10.1007/s00403-019-01960-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68.Yang FM, Fan D, Yang XQ, Zhu FH, Shao MJ, Li Q, Liu YT, Lin ZM, Cao SQ, Tang W, He SJ, Zuo JP. The artemisinin analog SM934 alleviates dry eye disease in rodent models by regulating TLR4/NF-κB/NLRP3 signaling. Acta Pharmacol Sin. 2021;42(4):593–603. doi: 10.1038/s41401-020-0484-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 69.Liu J, Manheimer E, Shi Y, Gluud C. Chinese herbal medicine for severe acute respiratory syndrome: a systematic review and meta-analysis. J Altern Complement Med. 2004;10(6):1041–1051. doi: 10.1089/acm.2004.10.1041. [DOI] [PubMed] [Google Scholar]
- 70.World Health Organization . SARS: clinical trials on treatment using a combination of traditional Chinese medicine and Western medicine. Geneva: World Health Organization; 2004. [Google Scholar]
- 71.National Administration of Traditional Chinese Medicine. The Traditional Chinese Medicine Prevention Program of Influenza A (H1N1) (2009). National Administration of Traditional Chinese Medicine, 2009 (in Chinese)
- 72.Luo H, Tang QL, Shang YX, Liang SB, Yang M, Robinson N, Liu JP. Can Chinese medicine be used for prevention of corona virus disease 2019 (COVID-19)? A review of historical classics, research evidence and current prevention programs. Chin J Integr Med. 2020;26(4):243–250. doi: 10.1007/s11655-020-3192-6. [DOI] [PMC free article] [PubMed] [Google Scholar]