| Objective: First of all,the purpose of this study was to systematically evaluate the effectiveness and safety of Yishen-Huoxue TCM prescription in the treatment of osteoarthritis,and to provide a scientific basis for the application of this treatment method in clinical practice.Secondly,through the study of network pharmacology and molecular docking technology,the mechanism of Yaotui-Tongning capsule in the treatment of osteoarthritis was discussed.The clinical trial data included in the past two years and the rabbit osteoarthritis model were reviewed to further evaluate the potential effect of this drug in the treatment of osteoarthritis,explore its intervention mechanism in the development process of osteoarthritis,and provide scientific basis for the development of more effective drugs for osteoarthritis.Methods:(1)The randomized controlled trial literature of Yishen-Huoxue TCM prescription for the treatment of osteoarthritis was studied through systematic review,and the adverse reactions,total effective rate and WOMAC score were demonstrated respectively.(2)TCMSP database was used to screen the active ingredients and corresponding targets of Yaotui-Tongning capsule,and OA targets were searched by integrating Gene Cardsda,Drug Bank,Pharm Gkb,OMIM and TTD databases.The interaction analysis of TCM-active ingredient-core target network and PPI protein network was constructed using STRING platform and Cytoscape software,and GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out.The molecular docking verification of important active ingredients and core targets was carried out using Py MOL and other software.(3)Retrospective analysis of 97 cases of patients with osteoarthritis treated with Yaotui-Tongning capsule in the past two years,description and analysis of the basic conditions of patients,evaluation of VAS score,WOMAC score and Lysholm index score of patients with osteoarthritis before and after treatment,and evaluation of clinical efficacy of traditional Chinese medicine.(4)The rabbit knee osteoarthritis model was established by injecting papain mixture into the left knee joint cavity,which was divided into Control group,OAM group,OAYTC group and OAXGC group.HE staining,ELISA and immunohistochemistry were used to determine the protective effect of Yaotui-Tongning capsule on rabbit articular cartilage injury.Meanwhile,Westerm-Blot was used to detect the expression of TLR4,My D88 and NF-κB related proteins,and the correlation analysis was performed.Results:(1)Systematic review of literature revealed that the Yishen-Huoxue TCM prescription group had higher total effective rate and lower adverse reaction rate than the western medicine group,and significantly improved the VAS score and Lysholm arthritis index,while there was no significant difference in WOMAC score and TCM symptom score.(2)A total of 80 active pharmaceutical chemical components were screened out;And disease intersection targets 99 of them,the core target for JUN,FOS,MAPK1,MAPK14,RELA,ESR1 and STAT3,etc.GO analysis showed that the key targets of Yaotui-Tongning capsule in the treatment of osteoarthritis were mainly related to the response to radiation,the response to nutrient level and the response to oxygen level.KEGG showed that the potential targets of Yaotui-Tongning capsule for OA were mainly concentrated in lipid and atherosclerosis,interleukin-17 signaling pathway,human cytomegalovirus infection and other pathways.Molecular docking showed that the main active ingredients of Yaotui-Tongning capsule had good binding activity with the key target of OA treatment.(3)The retrospective study revealed no statistically significant differences in gender,age,and disease duration among the five groups of syndrome types(P > 0.05),indicating comparability.Following treatment,there was a significant improvement in VAS score,WOMAC score,Lysholm score,and clinical efficacy evaluation for patients with knee osteoarthritis(P < 0.05).There were no notable variations in improvement observed among the five groups(P > 0.05).(4)Compared with Control group,the left knee joint motion in OAM group was significantly decreased(P<0.05),radiographs showed obvious narrowing of joint space and osteophyte formation in the left knee;The degree of cartilage injury and Mankin’s score were significantly increased(P<0.05),the levels of IL-1β,IL-6,PGE2 and TNF-α in serum and joint fluid were significantly increased(P<0.05).Compared with OAM group,both OAYTC group and OAXGC group had improved left knee joint motion(P<0.05),the degree of cartilage injury and Mankin’s score were significantly decreased(P<0.05),the levels of IL-1β,IL-6,PGE2 and TNF-α in serum and joint fluid were significantly decreased(P<0.05).Immunohistochemical method showed that MMP-3 and MMP-13 were expressed in Control group,OAM group,OAYTC group and OAXGC group,and more positive proteins were found in OAYTC group and OAXGC group,while the positive expressions of Control histone were not obvious.The relative expressions of TLR4,My D88 and NF-κB protein in the left knee cartilage of rabbits in all groups were detected by Wb method.Compared with OAM group,the expression levels of LR4,My D88 and NF-κB protein in OAYTC and OAXGC groups were decreased(P < 0.05).Conclusion: Tonifying kidney and activating blood can effectively reduce the pain symptoms of patients with osteoarthritis,improve the function of limb movement,and have high drug safety.As a drug for the treatment of osteoarthritis,Yaotui-Tongning capsule regulates the development of the disease from the aspects of multi-component,multi-target and multi-pathway,and its active ingredients play a curative effect by inhibiting inflammation,regulating apoptosis and reducing oxidative stress.The clinical treatment effect is remarkable and the drug safety is high.It improves the symptoms of osteoarthritis by intervening in the activation of TLR4/My D88/NF-κB signaling pathway,regulating inflammatory response and slowing the degeneration of cartilage. |
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