Jieduquyuziyin prescription alleviates SLE complicated by atherosclerosis via promoting cholesterol efflux and suppressing TLR9/MyD88 activation

Abstract

Ethnopharmacological relevance: Jieduquyuziyin prescription (JP), as a traditional Chinese medicine formula, is extensively applied to treat systemic lupus erythematosus (SLE). Its prescription is based on clinical practice and an evidence-based application of traditional medicines. It is approved by use in Chinese hospitals as a clinical prescription that can be directly used.

Aim of the study: The study aims to elucidate JP's efficacy on lupus-like disease combined with atherosclerosis and to explore its mechanism.

Materials and methods: To conduct in vivo experiments, we established a model of lupus-like disease with atherosclerosis in ApoE^-/- mice fed a high-fat diet and injected intraperitoneally with pristane. In addition, oxidized low-density lipoprotein (ox-LDL) and a TLR9 agonist (CpG-ODN2395) were utilized to examine the mechanism of JP on SLE combined with AS in RAW264.7 macrophages in vitro.

Results: Results indicated that JP reduced hair loss and levels of the spleen index, maintained stable body weight, alleviated kidney damage in mice, and reduced the expression levels of urinary protein, autoantibodies, and inflammatory factors in serum. Furthermore, JP is effective at alleviating the lupus-like symptoms observed in mice. In mice, JP inhibited aortic plaque deposition, stimulated lipid metabolism, and increased the expression of genes that regulate cholesterol efflux, including ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette subfamily G member 1 (ABCG1), scavenger receptor class B type I (SR-BI), and peroxisome proliferator-activated receptor γ (PPAR-γ). In vivo, JP inhibited the expression of the Toll-like receptor 9 (TLR9)-induced signaling pathway, which links TLR9/MyD88/NF-kB to the expression of subsequent inflammatory factors. Furthermore, JP inhibited the expression of TLR9 and MyD88 in vitro. In addition, the JP treatment effectively reduced foam cell formation in RAW264.7 macrophages by increasing the expression of ABCA1/G1, PPAR-γ and SR-BI.

Conclusions: JP played a therapeutic role in ApoE^-/- mice with pristane-induced lupus-like diseases and AS, possibly through inhibition of TLR9/MyD88 signaling and promotion of cholesterol efflux.

Keywords: Atherosclerosis; Inflammatory activation; Jieduquyuziyin prescription; Reverse cholesterol transport; Systemic lupus erythematosus; TLR9/MyD88 signal pathway.