ABSTRACT
BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear. OBJECTIVE: This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models. METHODS: The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings. RESULTS: Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1ß, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls. CONCLUSION: JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice.
.ABSTRACT
Objective To explore the value of MR T2 mapping imaging in evaluation of the effection of Zhitong-Jiangu recipes in treatment of cartilage injury in osteoarthritis.Methods The models of osteoarthritis in the knee of New Zealand white rabbits were made with intra-articular injection of papain.Totally 48 New Zealand white rabbits were randomly divided into normal control group,model control group,glucosamine hydrochloride treatment group and Zhitong-Jiangu recipes treatment group.MR T2 mapping was performed on the knee and the content of MMP-1 in articular cartilage was analyzed with immunohistochemistry 4 weeks after treatment.The differences of T2 value and MMP-1 content of articular cartilage among the four groups were compared.The correlation among the different intervention methods,MMP-1 content of articular cartilage and the T2 value of articular cartilage were analyzed.Results T2 value of articular cartilage in the model control group was significantly higher than that in the other three groups (all P＜0.01),and there was no significant difference of T2 value among the other three groups.The MMP-1 content of articular cartilage in glucosamine hydrochloride treatment group and Zhitong-Jiangu recipes treatment group was lower than that in model control group (both P＜0.05),and was higher than that in normal control group (both P＜0.05).There was no significant difference between the two groups.The relationship between MMP-1 content and T2 value of articular cartilage was nonlinear.With the increase of MMP-1 content,T2 value first increased slowly and then increased rapidly (P＜0.05).Conclusion MR T2 mapping imaging is helpful to evaluating the efficacy of Zhitong-Jiangu recipes in treatment of cartilage injury in osteoarthritis in rabbit models.The relationship between MMP-1 content and T2 value of articular cartilage may be nonlinear.
