Purpose of Review
Systemic lupus erythematosus (SLE) is a complex, potentially fatal autoimmune disease with no complete cure. Current treatments for SLE are limited by suboptimal efficacy and increased risk of infections and malignancies, and cannot meet the clinical demands of patients with SLE. Artemisinin and its derivatives (artemisinins), a new class of anti-malarial drugs, have recently been reported to have an immunosuppressive effect on lupus patients. In this review, we evaluate the therapeutic properties and potential mechanisms of artemisinins for the treatment of SLE.
Both clinical and animal studies suggest that artemisinins have potential beneficial effects for SLE. The beneficial effects associated with artemisinin treatment include improving symptoms, reducing level of antibodies and proteinuria, ameliorating renal damage, and diminishing the dosage of prednisone use. Animal studies suggest that mechanisms of action of artemisinins may include regulating T cell subsets, inhibiting activation of B cells and production of inflammatory cytokines, as well as blocking the NF-κB signal transduction pathway, thus playing a role in anti-inflammation and immunomodulation.
Artemisinin family drugs are a promising potential new medication that may challenge the current treatment paradigms available for SLE.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Davis LS, Reimold AM. Research and therapeutics-traditional and emerging therapies in systemic lupus erythematosus. Rheumatology. 2017;56:100–13.
Durcana L, Petrib M. Immunomodulators in SLE: clinical evidence and immunologic actions. J Autoimmun. 2016;74:73–84.
Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacol. 2015;23:231–69.
Wang C, Fortin PR, Li Y, Panaritis T, Gans M, Esdaile JM. Discontinuation of antimalarial drugs in systemic lupus erythematosus. J Rheumatol. 1999;26:808–15.
Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye. 2017;31:828–45.
Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf. 2017;16:411–9.
Lu YQ. The discovery and research progress of artemisinin. Life Science Research. 2012;16:260–5.
•• An J, Minie M, Sasaki T, Woodward JJ, Elkon KB. Antimalarial drugs as immune modulators: new mechanisms for old drugs. Annu Rev Med. 2017;68:317–30. This comprehensive review summarizes and updates the chemistry of artemisinin drugs and their mechanisms of action. The authors emphasize how artemisinin drugs may impact multiple pathways of innate immunity and their current and future impact on systemic lupus erythematosus.
Krishna S, Bustamante L, Haynes RK, Staines HM. Artemisinins: their growing importance in medicine. Trends Pharmacol Sci. 2008;29(10):520–7.
Yy T. The discovery of artemisinin (qinghao) and gifts from Chinese medicine. Nat Med. 2011;17:1217–20.
Schreiber A, Harter G, Schubert A, Bunjes D, Mertens T, Michel D. Antiviral treatment of cytomegalovirus infection and resistant strains. Exp Opin Pharmacother. 2009;10:191–209.
Cui X, Wang Y, Kokudo N, Fang D, Tang W. Traditional Chinese medicine and related active compounds against hepatitis B virus infection. Biosci Trends. 2010;4:39–47.
Jiang W, Li B, Zheng X, Liu X, Cen Y, Li J, et al. Artesunate in combination with oxacillin protect sepsis model mice challenged with lethal live methicillin-resistant Staphylococcus aureus (MRSA) via its inhibition on proinflammatory cytokines release and enhancement on antibacterial activity of oxacillin. Int Immunopharmacol. 2011;11(8):1065–73.
Gautam P, Upadhyay SK, Hassan W, Madan T, Sirdeshmukh R, Sundaram CS, et al. Transcriptomic and proteomic profile of Aspergillus fumigatus on exposure to artemisinin. Mycopathologia. 2011;172:331–46.
Xu LG, Chen P, Liang JS, Yi M, Wang Q, Ouyang D, et al. Therapeutic effect and mechanism of artesunate on experimental pulmonary fibrosis in rats. Clinical Medical Engineering. 2009;16(9):6–8.
Wang XQ, Liu HL, Wang GB, Wu PF, Yan T, Xie J, et al. Effect of artesunate on endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2011;52:916–9.
Ho WE, Peh HY, Chan TK, Fred Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacology & Therapeutics. 2014;142:126–39.
Daniels TR, Bernabeu E, Rodríguez JA, Patel S, Kozman M, Chiappetta DA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta. 2012;1820:291–317.
• Lin ZM, Yang XQ, Zhu FH, He SJ, Tang W, Zuo JP. Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells. Sci Rep. 2016;29(6):38115. This study demonstrates the immunosuppressive effects of artemisinin analogue SM934 on collagen-induced arthritis both in vitro and in vivo.
Snyder MR. Commentary on “Inhibitory effect of the antimalarial agent artesunate on collagen-induced arthritis in rats through nuclear factor kappa B and mitogen-activated protein kinase signaling pathway”. Transl Res. 2013;161(2):85–8.
Cui XJ, Wang YY, Hou XQ, Pan L, Fu JX. Clinical observation of artesunate in the treatment of rheumatoid arthritis. Chin J Hosp Pharm. 2007;27(5):645–6.
Wei S, Xu GG. Clinical observation of artesunate in the treatment of rheumatoid arthritis. Shanxi Journal of Medicine. 2008;37(5):457–8.
Yu QB, Jin HL. Artesunate treatment on dermatosis: a clinical analysis of 90 cases. Journal of Bengbu Medical College. 1997;22(5):309–10.
Zhou Q, Gao YX, Jin HL. Effects of artesunate on experimental immunological myositis in animal model (in Chinese). Chinese Journal of Dermatology. 1998;31(4):241–3.
Ma J, Chen LH, Liao R, Xu SG, Li M, Xu DH, et al. Effect of artemether and dihydroartemisinin on scleroderma in mice. Chin J Chin Mat Med. 2009;34(2):204–7.
Golenser J, Waknine JH, Krugliak M, Hunt NH, Grau GE. Current perspectives on the mechanism of action of artemisinins. Int J Parasitol. 2006;36:1427–41.
Zhong JX, Peng SQ, Zhang JY, Liang LQ. 25 cases of SLE treated with combination of traditional Chinese and western medicine. Chinese Journal of Integrated Traditional and Western Medicine. 1999;19(1):47–8.
Zhang JY, Zhong JX, Shi ZY, Dai XY. Effect of artesunate and Lingdan tablet on T cell subsets in SLE patients. Chinese Journal of Integrated Traditional and Western Medicine. 2002;22(7):489.
Zhang JY, Zhong JX, Peng SQ, Zhang FX. Study on the effect of artesunate and Lingdan tablet on IL-2 and sIL-2R in patients with SLE. Journal of Henan University of Chinese Medicine. 2003;18(2):38–9.
Lu L. Study on effect of artemisinin and cordyceps sinensis in preventing recurrence of lupus nephritis. Chinese Journal of Integrated Traditional and Western Medicine. 2002;22(3):169–71.
Huang XX. Clinical study of artesunate on immune function in patients with SLE. Lishizhen Medicine and Materia Medica Research. 2011;22(7):1673–4.
Yu QB, Gao YX. Clinical observation of artesunate in the treatment of 56 cases of lupus. Chinese Journal of Dermatology. 1997;30(1):51–2.
Yu QB, Jin HL. Clinical observation of artesunate in the treatment of 30 cases of SLE. Journal of Bengbu Medical College. 1996;21(3):173–4.
Chinese society of integrated Chinese and western medicine on dermatology. Five kinds of dermatological diseases: diagnosis and evaluation criteria of integrated traditional Chinese and western medicine. Chinese Journal of Integrated Traditional and Western Medicine. 1992;12(1):56–8.
Wu XL, Zhang WG, Shi XM, An P, Sun WS, Wang Z. Therapeutic effect of artemisinin on lupus nephritis mice and its mechanisms. Acta Biochim Biophys Sin. 2010;42:916–23.
Wu XL, Sun WS, Shi XM, Wang Z, An P, Qiao CL. Effect of artemisinin on the expressions of GRαmRNA, GRβmRNA and P300/CBP protein in lupus nephritis mice. Journal of Chinese Medical Materials. 2012;35:608–12.
•• Liang N, Zhong YC, Zhou J, Liu BH, Lu RR, Guan YZ, et al. Immunosuppressive effects of hydroxychloroquine and artemisinin combination therapy via the nuclear factor-κB signaling pathway in lupus nephritis mice. Exp Ther Med. 2018;15:2436–42. This study demonstrates the immunosuppressive effect of artemisinin and hydroxychloroquine combination therapy, which may provide a novel method for the treatment of lupus nephritis. The underlying mechanisms of the combined treatment may be through regulation of the expression levels of cytokines, KLF15 and NF-kB.
Xu LM, Chen XR, Tu YY. Effect of dihydroartemisinin on BXSB lupus mice. Chinese Journal of Dermatovenereology of Integrated Traditional and Western Medicine. 2002;1:19–20.
Dong YJ, Li WD, Tu YY, Zou WZ, Xi HL, Lin ZB. Effect of dihydroartemisinin on autoantibodies production, TNFα secretion and pathological changes of lupus nephritis in BXSB lupus mice. Chinese Journal of Integrated Traditional and Western Medicine. 2003;23:676–9.
Dong YJ, Li WD, Tu YY, Zhang HN, Zou WZ, Yang LL, et al. Effect and mechanism of dihydroartemisinin on BXSB lupus mice. Chinese Pharmacological Bulletin. 2003;19:1125–8.
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;6:1243–50.
Huang XQ, Xie ZJ, Liu FF, Han CW, Zhang DY, Wang DW, et al. Dihydroartemisinin inhibits activation of the Toll-like receptor 4 signaling pathway and production of type I interferon in spleen cells from lupus-prone MRL/lpr mice. Int Immunopharmacol. 2014;22:266–72.
You YW, Liao PH, Yang FF, Lin X. Regulating effect of dihydroartemisinin on expression of fractalkine in renal cortex of lupus-prone MRL/lpr mice. Immunological Journal. 2014;30(7):617–22.
• Huang M, Jin XK, Cai QC, Li M, Lin ZB, Li WD. Effect of dihydroartemisinin on lupus mice and its relationship with SIGIRR induced immune negative regulation. Chinese Journal of Immunology. 2015;31:1637–41. 1647. The authors observe the relationship between the therapeutic effect of dihydroartemisinin and its molecular mechanism and signal pathway in lupus mouse model.
Zhu WX, Gu J. Effects of artesunate on interleukin-6 and transforming growth factor β in renal tissue of lupus-like mice. Chinese Journal of Dermatovenereology of Integrated Traditional and Western Medicine. 2003;2:25–7.
Zhu WX, Gu J. Effects of artesunate on serum level of interleukin-6 and transforming growth factor β in lupus-like mice. Chinese Journal of leprosy and skin diseases. 2004;20:318–9.
Jin OY, Zhang HY, Xu T, Zhao SN, Zhou KX, Sun LY. Pathological change and mechanism of artesunate treatment for lupus nephritis in MRL/lpr mice. Journal of Clinical Medicine in Practice. 2007;11(4):5–9.
Lin XD, Zhong JX, Qi SJ, Zhang FX. Effects of artesunate on the expression of CD4, CD8 and CD54 on peripheral blood lymphocytes in lupus like mice. Shandong J Tradit Chin Med. 2008;27:615–7.
Jin OY, Zhang HY, Gu ZF, Zhao SN, Xu T, Zhou KX, et al. A pilot study of the therapeutic efficacy and mechanism of artesunate in the MRL/lpr murine model of systemic lupus erythematosus. Cellular & Molecular Immunology. 2009;6:461–7.
Wang H, Jiang B, Zhang HY, Liu BJ, Sun LY. Artesunate relieves lupus nephritis by inhibiting the expression of ICAM-1. Journal of Clinical Medicine in Practice. 2010;14(7):1–3.
Hou LF, He SJ, Li X, Yang Y, He PL, Zhou Y, et al. Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses. Arthritis Rheum. 2011;63:2445–55.
Hou LF, He SJ, Li X, Wan CP, Yang Y, Zhang XH, et al. SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development. PLoS One. 2012;7(2):e32424.
•• Wu YW, He SJ, Bai BX, Zhang LY, Xue L, Lin ZM, et al. Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation. Cell Mol Immunol. 2016;13:379–90. This study investigates the therapeutic effects of a modified dosage regimen of artemisinin analogue SM934 on lupus-prone MRL/lpr mice and explores its effects on B cell responses in SLE. The authors conclude that a twice daily dosing regimen of SM 934 has therapeutic effects on lupus-prone MRL/lpr mice by suppressing B cell activation and plasma cell formation.
Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390.
Jyonouchi H, Kincade PW, Good RA. Age-dependent changes in B lymphocyte lineage cell populations of autoimmune-prone BXSB mice. J Immunol. 1985;134(2):858–64.
•• Feng X, Chen W, Xiao L, Gu F, Huang J, Tsao BP, et al. Artesunate inhibits type I interferon-induced production of macrophage migration inhibitory factor in patients with systemic lupus erythematosus. Lupus. 2017;26(1):62–72. These authors report the effects and potential immune mechanisms of artesunate and find that artesunate inhibits macrophage migration inhibitory factor, and thus may have therapeutic potential for SLE-associated atherosclerosis.
Zani B, Gathu M, Donegan S, Olliaro PL, Sinclair D. Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2014;20(1):1–160.
• Kovacs SD, van Eijk AM, Sevene E, Dellicour S, Weiss NS, Emerson S, et al. The safety of artemisinin derivatives for the treatment of malaria in the 2nd or 3rd trimester of pregnancy: a systematic review and meta-analysis. PLoS One. 2016;11(11):e0164963. This study provides a comprehensive review of the safety of artemisinin derivatives for the treatment of malaria during pregnancy.
Toovey S, Jamieson A. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg. 2004;98(5):261–7.
Hutagalung R, Htoo H, Nwee P, Arunkamomkiri J, Zwang J, Carrara VI, et al. A case-control auditory evaluation of patients treated with artemether-lumefantrine. Am J Trop Med Hyg. 2006;74(2):211–4.
Aceng JR, Byarugaba JS, Tumwine JK. Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial. BMJ. 2005;330(7487):334.
Nosten F, McGready R, d'Alessandro U, Bonell A, Verhoeff F, Menendez C, et al. Antimalarial drugs in pregnancy: a review. Curr Drug Saf. 2006;1(1):1–15.
McGready R, Lee SJ, Wiladphaingern J, Ashley EA, Rijken MJ, Boel M, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012;12:388–96.
• von Hagens C, Walter-Sack I, Goeckenjan M, Osburg J, Storch-Hagenlocher B, Sertel S, et al. Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat. 2017;164(2):359–69. This study describes safety of use oral artesunate and emphasizes that safety monitoring should include reticulocytes, audiological and neurological exploration for cancer patients.
Dr. Wang is supported by the National Center for Complementary and Integrative Health (K24 AT007323).
Dr. Wang is supported by the National Center for Complementary and Integrative Health of the National Institutes of Health (NIH, R01AT006367, R01AT005521 and K24AT007323). “The organizations above did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The investigators are solely responsible for the content of the manuscript and the decision to submit for publication.”
Dr. Mu is supported by the China Academy of Chinese Medical Sciences, Guang’anmen Hospital, Beijing.
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Complementary and Alternative Medicine
About this article
Cite this article
Mu, X., Wang, C. Artemisinins—a Promising New Treatment for Systemic Lupus Erythematosus: a Descriptive Review. Curr Rheumatol Rep 20, 55 (2018). https://doi.org/10.1007/s11926-018-0764-y
- Systemic lupus erythematosus
- Lupus nephritis
- Anti-malarial drug
- Artemisinin derivatives (Artemisinins)