Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in KOA treatment. Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

Osteoporosis (OP) is a metabolic bone disease characterized by reduced bone mass and impaired bone microstructure, leading to an increased risk of fractures. In this context, the Gusongan (GSA) capsule has gained recognition for its osteogenic potential. This study sought to examine the therapeutic effects of GSA capsule on OP and to elucidate the molecular mechanisms underpinning its osteoprotective properties. An OP model was established in female Sprague-Dawley rats through bilateral ovariectomy (OVX), followed by gavage administration of varying doses of GSA capsule. The study included the control, OVX model, and positive control (alendronate) groups. Bone mineral density (BMD) and serum biomarkers of rats were analyzed using micro-computed tomography (micro-CT) and enzyme-linked immunosorbent assay (ELISA). RNA sequencing (RNA-seq)- and network pharmacology-based analyses were conducted to identify potential molecular targets. Additionally, in vitro experiments were performed to evaluate the impacts of GSA capsule on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the TLR2/NF-κB pathway. Micro-CT analysis demonstrated that GSA capsule treatment markedly improved BMD, trabecular number (Tb.N), and bone volume/total volume (BV/TV), while reducing trabecular separation (Tb.Sp) (p< 0.05). ELISA results further revealed that GSA capsule diminished serum levels of bone Gla protein (BGP), bone alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRACP) in OVX rats (p< 0.05), suggesting an inhibitory effect on bone resorption and turnover. RNA-seq- and network pharmacology-based analyses highlighted the downregulation of key factors in the TLR2/NF-κB pathway in BMSCs following GSA capsule treatment. Furthermore, GSA capsule enhanced BALP activity and mineralized nodule formation in BMSCs (p< 0.05). In vitro investigations corroborated that GSA capsule downregulated TLR2 and NF-κB p65 levels and fostered the expression of osteogenic genes, including COL1A1, RUNX2, and OPN (p< 0.05). This study highlighted that GSA capsule attenuated inflammation and augmented osteogenic differentiation of BMSCs by targeting the TLR2/NF-κB pathway. These molecular mechanisms contributed to enhanced BMD and bone microarchitecture in OVX rats, suggesting the therapeutic potential of GSA capsule in OP management.