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Quercetin, a typical flavonoid derived from a common natural plant, has multiple biological activities. Previous research in animal models has demonstrated the effectiveness of quercetin in treating rheumatoid arthritis (RA). The pharmacological effects and probable mechanisms of quercetin were evaluated in this study. Three databases, PubMed, Web of Science, and Embase, were searched for relevant studies from the creation of the databases to November 2022. Methodological quality was assessed using the SYRCLE risk of bias tool. STATA 15.1 was used to perform the statistical analysis. This research included 17 studies involving 251 animals. The results indicated that quercetin was able to reduce arthritis scores, paw swelling, histopathological scores, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), C-reactive protein (CRP), malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), nuclear factor kappa B (NF-kB) and increase interleukin-10 (IL-10), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1). These may be related to quercetin's potential anti-inflammatory, anti-oxidative stress, and osteoprotective properties. However, more high-quality animal studies are needed to assess the effect of quercetin on RA. Additionally, the safety of quercetin requires further confirmation. Given the importance of the active ingredient, dose selection and the improvement of quercetin's bioavailability remain to be explored. [ABSTRACT FROM AUTHOR]

Guizhi-Shaoyao-Zhimu decoction (GSZD), a classic Chinese herbal formula, can reportedly ameliorate clinical rheumatoid arthritis (RA) symptoms without serious adverse effects. We performed a systematic review and meta-analysis of randomised controlled trials to assess the effect and safety of GSZD for treating RA. We systematically searched for such randomised controlled trials, which compared GSZD with common treatments for RA, in PubMed, Embase, the Cochrane Library, Web of Knowledge, the VIP database, the China National Knowledge Infrastructure, Wanfang, Baidu Scholar, Google Scholar, and the Chinese Biomedical Database. The main index for evaluating the curative effects was the total clinical effective rate; the secondary indicators were sign changes (morning stiffness time, joint swelling index, joint tenderness index, swollen joint count) and laboratory indicators (erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor). We retrieved a total of 708 studies and included 10 in our analysis (n = 792). Compared with conventional drugs, GSZD was more likely to achieve clinical efficacy (relative risk = 1.19; 95% CI: 1.12-1.26) and significantly improve the patient's physical signs. In addition, GSZD exhibited a likelihood of reducing the incidence of adverse events by 73% compared with the control (relative risk = 0.27; 95% CI: 0.09, 0.77). Altogether, we provide evidence that GSZD is an effective and safe drug for treating RA clinically. [ABSTRACT FROM AUTHOR]

Guizhi Shaoyao Zhimu decoction, a traditional Chinese medicine formula used empirically for the treatment of rheumatoid arthritis (RA), has been shown to alleviate bone destruction in rats with collagen-induced arthritis (CIA). The aim of this study is to characterize the effects of Guizhi Shaoyao Zhimu granules (GSZGs) on bone destruction in RA and the underlying mechanism. A CIA arthritis model using DBA/1 mice. The animals were divided into a normal group; CIA model group; low, medium, and high-dose GSZG groups (3, 6, and 9 g/kg/day); and a methotrexate group (1.14 mg/kg/w). In vitro , a cytokine induced osteoclastogenesis model was established. After 28 days of treatment, the paw volume was measured, bone destruction was examined by micro-CT, and the generation of osteoclasts in bone tissue was evaluated via tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, the inhibitory effect and underlying mechanism of action of GSZG on RANKL-induced osteoclastogenesis were investigated in vitro. The in vivo analyses demonstrated that the paw volume and degree of bone erosion of mice in the medium- and high-dose GSZG groups were significantly decreased compared to the CIA model group. In addition, GSZG treatment suppressed the excessive generation of osteoclasts in the bone tissue of CIA mice. In vitro , GSZG inhibited RANKL-induced osteoclastogenesis and osteoclast-mediated bone resorption. Specifically, it only inhibited the generation of osteoclast precursors (OCPs); it had no significant effect on the fusion of OCPs or maturation of osteoclasts. Finally, we showed that the inhibitory effect of GSZG on osteoclastogenesis was related to the promotion of PTEN-induced kinase protein 1 (PINK1)/Parkin pathway-mediated mitophagy of osteoclast precursors, which was verified using a PINK1 knockdown small interfering RNA in OCPs. These findings indicate that GSZG is a candidate for the treatment of bone destruction in RA and provide a more detailed elucidation of the mechanism of GSZG anti-RA bone erosion, i.e. , inhibition of the ROS/NF-κB axis through the PINK1/Parkin-mediated mitochondrial autophagic pathway to inhibit osteoclast precursor production, compared to the published literature. [Display omitted] [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a known intractable chronic inflammatory disease of synovial joints characterized by hyperplasia and consecutive inflammation with a high prevalence. Guizhi-Shaoyao-Zhimu (GSZD) is the first choice for clinical treatment of RA in Chinese traditional medicine. This study is aimed to explore the possible pharmacological mechanisms of anti-arthritic effect of GSZD. Type II collagen-induced arthritis (CIA) rat model was used to study the anti-arthritic activity of GSZD in vivo , and toe swelling & arthritis score, serum levels of cytokines, and pathological examinations were carried out. In vitro , TNF-α induced MH7A cells were used to study the possible mechanisms of GSZD. The anti-proliferative effects of GSZD were determined by MMT assay, and pro-apoptotic activity of GSZD in MH7A cells was determined by flow cytometry analysis & DAPI staining. Furthermore, the adhesive and invasive abilities of MH7A cells were determined using cell adhesion and transwell assays. MMPs levels were determined by ELISA assays, and mRNA expressions of Caspase-3, -9, Bax, SOCS1, Bcl-2, JAK2, STAT-3 and -5 were determined using qRT-PCR analysis. Besides, the major chemical components in GSZD were analyzed by HPLC-QqQ-MS analysis. Our results showed GSZD reduced the toe swelling & arthritis score, and serum levels of TNF-α, IL-1β, IL-6 & IL-17a in CIA rats; pathological examination results indicated GSZD improved ankle joint injury in CIA rats. In vitro , GSZD showed significant anti-proliferative and pro-apoptotic effects on TNF-α stimulated MH7A cells. After GSZD treatment, the adhesive and invasive abilities of MH7A cells were reduced, and secretions of MMPs, IL-6 and IL-8 were also reduced. GSZD decreased the releases of TNF-α and IL-1β in LPS stimulated RAW 264.7 cells. Further studies showed GSZD up-regulated mRNA expressions of Caspase-3, -9, Bax, and SOCS1, whereas down-regulated mRNA expressions of Bcl-2, JAK2, STAT3 and STAT5. Besides, 13 major chemical components were identified in GSZD extracts through HPLC-QqQ-MS analysis. Our results suggested GSZD possesses an anti-rheumatic effect on CIA rats, and the possible mechanism is related to inhibiting inflammatory response, inhibiting invasion and migration of synovial fibroblasts, and inducing apoptosis in synovial fibroblasts. [ABSTRACT FROM AUTHOR]