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.
This study aimed to investigate whether shikonin combined with methotrexate could inhibit psoriasis progression by regulating the polarization of macrophages through in vivo and in vitro experiments. Imiquimod was administrated to the exposed skin of BALB/c mice, and shikonin and methotrexate suspension were also given by gavage. The erythema, scales and thickness were scored for mice lesions in each group, and the total score was obtained by adding the above three scores, and calculated as psoriasis area and severity index (PASI) score. The skin lesion tissue from mice was isolated and used for hematoxylin-eosin staining and immunohistochemistry assay. Drug-containing serum was prepared and administrated into mouse macrophage RAW264.7 cells, followed by simulation of LPS. The levels of tumor necrosis factor-α (TNF-α), Interleukin (IL)-1β, and IL-6 in cell supernatant were assessed using ELISA Kits and real-time PCR. In imiquimod-induced psoriasis mice, shikonin combined with methotrexate exerted protective effects by reducing erythema and PASI scores, decreasing backer score and epidermal thickness, and particularly regulating macrophage polarization. In LPS-stimulated RAW264.7 cells, shikonin combined with methotrexate regulated M1/M2 polarization and altered the levels of M1 markers. Shikonin combined with methotrexate inhibit psoriasis progression by regulating the polarization of macrophages, which may be useful in the treatment of psoriasis.
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