Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) and one of the leading causes of death. An alternative effective treatment to ameliorate and relieve LN and delay the process of renal tissue fibrosis is urgently needed in the clinical setting. Jieduquyuziyin prescription (JP) has been successfully used to treat SLE, but its potential mechanisms are not sufficiently understood. In this study, we treated MRL/lpr mice with JP for 8 weeks and treated human renal tubular epithelial cells (human kidney 2 (HK-2)) with drug-containing serum to observe the antagonistic effects of JP on inflammation and fibrosis, as well as to investigate the possible mechanisms. Results demonstrated that JP significantly reduced urinary protein and significantly improved pathological abnormalities. Metabolomics combined with ingenuity pathway analysis illustrated that the process of kidney injury in lupus mice may be closely related to farnesoid X receptor (FXR) pathway abnormalities. Microarray biomimetic analysis and LN patients indicated that FXR may play a protective role as an effective therapeutic target for LN and renal fibrosis. JP significantly increased the expression of FXR and inhibited the expression of its downstream targets, namely, nuclear transcription factor κB (NF-κB) and α-smooth muscle actin (α-SMA), in the kidney of MRL/lpr mice and HK-2 cells, as confirmed by in vitro and in vivo experiments. In conclusion, JP may mediate the activation of renal FXR expression and inhibit NF-κB and α-SMA expression to exert anti-inflammatory and antifibrotic effects for LN prevention and treatment.

T cell subsets play a critical role in immune regulation. T helper 17 (Th17) cells induce tissue inflammation and autoimmune response while regulatory T (Treg) cells mediate autoimmune tolerance and inhibit autoimmune response. Recent studies have shown that the important factors for the pathogenesis and disease activity of systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, are an increased number of Th17 cells and a decreased number or reduced functions of Treg cells. Triptolide is the main active ingredient of Tripterygium wilfordii Hook F (TWHF). It not only has anti-inflammatory, antiproliferative, immune modulation, and proapoptotic activity effects, but is also effective in treating SLE. However, the underlying mechanism of how triptolide works is still unclear. For the purpose of evaluating the impact of triptolide on the induction of Th17 and Treg cells, we conducted relevant experiments with respect to the number and activities of Th17 and Treg cells in vivo and in vitro. In vivo, intragastrically administered triptolide effectively ameliorated the clinical and histological symptoms in lupus-like mice, increased the number of induced Treg cells and reduced the number of Th17 cells in the spleen and their secretion. In vitro, triptolide is able to promote the differentiation of Treg cells and inhibit Th17 formation by inhibiting the AKT/mTOR/p70S6K pathway. Therefore, we posit that triptolide can help to deter the development of inflammation and ultimately treat SLE through regulation of the Th17 and Treg cells balance.