Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance

Abstract

The Treg/Th17 imbalance is associated with the development of systemic lupus erythematosus (SLE). Dihydroartemisinin (DHA), a semi‐synthetic derivative of artemisinin, is isolated from the traditional Chinese herb Artemisia annua Artemisia annua L. This study aims to evaluate the effects of DHA alone or in combination with prednisone in immunodeficiency of SLE. In vivo, the therapeutical effect of DHA alone or in combination with prednisone was assessed in the pristane‐induced SLE mouse model. Then, the level of serum antibodies, creatinine (Cre), blood urea nitrogen (BUN), urine protein, kidney histopathology, interleukin (IL)‐17, IL‐6, transforming growth factor (TGF)‐β, the expression of RORγt and Foxp3, the percentages of Treg and Th17 in peripheral blood and spleen were assayed. In vitro, the mouse spleen lymphocytes were separated and treated with DHA alone or DHA in combination with prednisone. Then the percentages of Treg and Th17, the concentration of IL‐17, IL‐6, TGF‐β, and the expression of RORγt and Foxp3 were assayed. It was shown that DHA alone or in combination with prednisone treatment significantly alleviated the manifestations of pristane‐induced SLE mice, suppressed inflammation and restored the Treg/Th17 balance. DHA alone or in combination with prednisone significantly inhibited Th17 cell differentiation while induced Treg cell differentiation in vitro. DHA alone or in combination with prednisone also reduced the transcription of RORγt and increased Foxp3 in lymphocytes, as well as IL‐17 and TGF‐β levels. Our data indicated that DHA can produce synergistic effect with prednisone to attenuate the symptoms of SLE by restoring Treg/Th17 balance.

Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs

“…Li et al showed that senescence of myeloid-derived suppressor cells (MDSCs) promoted the pathogenesis of SLE, while dihydroartemisinin alleviated the manifestation of SLE by attenuating MDSC senescence via regulating Nrf2/HO-1 pathway ( 54 ). Subsequently, it was demonstrated that dihydroartemisinin alone, or in combination with prednisone treatment, significantly ameliorated the signs and symptoms of murine SLE through restoring the Treg/Th17 balance by reducing transcription of RORγt and increasing expression of Foxp3 in T cells ( 55 ). Serum levels of Macrophage migration inhibitory factor (MIF) in SLE patients were positively associated with the disease activity.…”

Yunnan Baiyao Ameliorates Rheumatoid Arthritis in Rats by Shifting the Th17/Treg Cell Balance and Preventing Osteoclast Differentiation

“…The Th17/Treg cell imbalance not only plays a key role in RA but also plays an important role in systemic lupus erythematosus (SLE) and uveitis. The changes in cytokines secreted by Th17 and Treg cells are closely correlated with the pathogenesis of SLE and uveitis [ 22 , 23 ]. Therefore, we isolated spleen lymphocytes from different groups of RA rats and analyzed the Th17/Treg cell ratio by flow cytometry.…”

Dihydroartemisinin ameliorates palmitate-induced apoptosis in cardiomyocytes via regulation on miR-133b/Sirt1 axis

“…The functions of artemisinin mainly focus on the regulation of allergy, anti-allergy, immune regulation and fever suppression and detoxification (Çapcı et al, 2021). Recent studies have shown that artemisinin has a certain effect on systemic lupus erythematosus (Chen et al, 2021;Lin et al, 2021). Artemisinin exhibited anti-inflammatory activity and lowered the systemic levels of inflammatory cytokines that resulted in cytokine storm and inflammatory organ injury in high-risk COVID-19 patients (Uckun et al, 2021).…”