Guizhi-Shaoyao-Zhimu decoction attenuates bone erosion in rats that have collagen-induced arthritis via modulating NF‐κB signalling to suppress osteoclastogenesis

Abstract

Context Guizhi-Shaoyao-Zhimu decoction (GSZD) is commonly used to treat rheumatoid arthritis (RA), but its mechanism is unclear. Objective To investigate the effect of GSZD on bone erosion in type II collagen (CII)-induced arthritis (CIA) in rats and to identify the underlying mechanism. Materials and methods The CIA model was prepared in male Wistar rats by two subcutaneous injections of CII, 1 mg/mL. Fifty CIA rats were randomized equally into the control group given saline daily, the positive group given saline daily and methotrexate 0.75 mg/kg once a week, and three GSZD-treated groups gavaged daily with 800, 1600 and 3200 mg/kg of GSZD for 21 days. GSZD effects were assessed by paw volume, arthritic severity index and histopathology. Cytokine levels were determined by ELISA. The effects of GSZD on RAW264.7 cells were evaluated by receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption assay. Expression of IκB-α and p65 was measured by Western blotting. Major components of GSZD were identified by HPLC. Results Arthritis index score, paw volume and bone destruction score showed that GSZD improved inflammatory symptoms and reduced joint tissue erosion ( p < 0.01). GSZD decreased RANKL, and the number of osteoclasts (OCs) in joint tissues ( p < 0.01) and increased osteoprotegerin levels ( p < 0.01). GSZD inhibited RANKL-induced RAW264.7 differentiation and reduced bone resorption by OCs. GSZD upregulated IκB ( p < 0.01) and p65 ( p < 0.01) in the cytoplasm and downregulated p65 ( p < 0.01) in the cell nucleus. Conclusions Guizhi-Shaoyao-Zhimu decoction has an anti-RA effect, suggesting its possible use as a supplement and alternative drug therapy for RA.

Synergistic impact of Gui Zhi Shao Yao Zhi Mu Decoction and leflunomide on gut microbiota in rheumatoid arthritis: insights from 16S rDNA sequencing

“…The decreased pathways in the LEGZ group might reflect GSZD's regulation of abnormal metabolism in the intestine. In vitro experiments demonstrated GSZD's ability to reduce inflammatory factor release in LPS-stimulated RAW 264.7 cells [55], disrupt the RA disease dysfunction module, and restore in vivo homeostasis [56]. These results highlight significant metabolic pathway differences between the intestinal flora of the LEF and LEGZ groups, possibly due to GSZD's complex composition and broader impact compared to LEF.…”

TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter

“…For instance, Guizhi-Shaoyao-Zhimu decoction, traditionally utilized in TCM for managing “Bi Zheng” exhibited the ability to diminish neutrophil recruitment and lower the concentrations of IL-6, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) ( Zhang et al, 2019b ). It also hindered the activation of NF-κB signaling pathways by reducing p-IKKβ and p-p65 levels, augmenting IκBα levels, and mitigating NF-κB’s binding to DNA ( Wei et al, 2021 ). Consequently, this formulation effectively shielded mice induced by MSU from inflammation ( Zhou et al, 2022a ).…”

Advances in Experimental and Clinical Research of the Gouty Arthritis Treatment with Traditional Chinese Medicine

“…Articular chondrocytes apoptosis inhibition is a new method for the treatment of gouty arthritis. Formulas such as Jiawei Simiao powder [ 52 ] and Guizhi Shaoyao Zhimu decoction [ 53 ] and herbs including Phellodendri Chinrnsis Cortex (Huang bai) [ 54 ] and Rhizoma Atrac-tylodis Lanceae (Cang zhu) [ 55 ] can significantly inhibit articular chondrocytes apoptosis and have an antigout effect. The compounds isolated from Radix Rhei Et Rhizome (Da huang) [ 56 ] and Stephaniae Tetrandrae Radix (Fang ji) [ 57 ] can inhibit the inflammatory reaction of cells and regulate the immunity and metabolism of the human body.…”