中药药理与临床2025，Vol.41Issue(5)：9-14,6.
基于网络药理学和实验验证探讨骨痨愈康丸含药血清干预类风湿关节炎骨破坏的作用机制
Mechanism of Serum Containing Gulao Yukang(骨痨愈康)Pills in Intervening in Bone Destruction in Rheumatoid Arthritis Based on Network Pharmacology and Experimental Validation
摘要
Abstract
Objective:To explore the mechanism of action of Gulao Yukang(骨痨愈康)Pills-containing serum in intervening in bone destruction in rheumatoid arthritis based on network pharmacology and experimental validation.Methods:Traditional Chinese Medicine Systems Pharma-cology Database and Analysis Platform(TCMSP)and the bioinformatics analysis tool of molecular mechanism of Chinese medicine were used to screen the active ingredients of Chinese medicine in Gulao Yukang Pills and their related targets.Genes targeting diseases related to bone destruction in rheumatoid arthritis were screened,and a diagram of"drug-ingredient-target-disease"network was constructed.The model was established in RAW 264.7-induced osteoclasts,and the low-,medium-,and high-dose Gulao Yukang Pills-containing serum was used for inter-vention.The proliferation of RAW 264.7 cells was detected by CCK-8 assay,and the content of TNF-α,MMP-3,and IL-1β was detected by ELISA in the supernatant of the cells.The protein expression of cellular C-FOS,NFATC1,NF-κB p65,p-NF-κB p65,IκBα,and p-IκBα was detected by Western blotting,and immunofluorescence staining was used to detect NF-κB p65 nuclear translocation.Results:Through the net-work pharmacology database and the bioinformatics analysis tool of the molecular mechanism of Chinese medicine,47 potential targets and 184 active ingredients of Gulao Yukang Pills for the treatment of bone destruction in rheumatoid arthritis were obtained,involving main active in-gredients quercetin,Ginkgo biloba ketone,and lysine β-sitosterol.Key targets were cellular inflammatory factors TNF and IL-17.The biologi-cal processes involved the response to cytokines and bone destruction,and the main pathways involved NF-κB,PI3K/AKT,etc.Based on the results of cell experiments,compared with the results in the blank control group,the content of TNF-α,MMP-3,and IL-1β was significantly in-creased in the model control group(P<0.05),and the protein expression levels of C-FOS,NFATC1,NF-κB p65,and p-NF-κB p65 were up-regulated(P<0.05).Moreover,the protein expression of p-IκBα was downregulated(P<0.05),and the expression of NF-κB p65 in the cell nucleus was upregulated(P<0.05).Compared with the results in the model control group,the cell content of TNF-α,MMP-3,and IL-1β in Gulao Yukang Pills-containing serum groups with different doses was significantly decreased(P<0.05),and the protein expression levels of C-FOS,NFATC1,NF-κB p65,and p-NF-κB p65 in the cells of 10%drug-containing serum groups at doses of 0.95 g/kg and 1.90 g/kg were downregulated(P<0.05).In Gulao Yukang Pills-containing serum groups with different doses,the p-IκBα expression was upregulated(P<0.05),while the expression of NF-κB p65(red)in the cell nucleus was downregulated(P<0.05).Conclusions:Gulao Yukang Pills can inhibit the activation and phosphorylation expression of C-FOS,NFATC1,NF-κB p65,and IκBα,reduce the secretion of inflammatory media-tors,inhibit the nuclear translocation of NF-κB p65,and regulate the NF-κB signaling pathway to play a protective role in bone destruction in rheumatoid arthritis.关键词
骨痨愈康丸/类风湿关节炎/骨破坏/网络药理学/核因子κB信号通路Key words
Gulao Yukang(骨痨愈康)Pills/Rheumatoid arthritis/Bone destruction/Network pharmacology/NF-κB signaling pathway引用本文复制引用
田杰祥,王钢,宋敏,漆文霞,姜刚刚,李平顺,贺童,魏勇,安文博..基于网络药理学和实验验证探讨骨痨愈康丸含药血清干预类风湿关节炎骨破坏的作用机制[J].中药药理与临床,2025,41(5):9-14,6.基金项目
国家自然科学基金地区基金资助项目(编号:81960832) （编号:81960832）
甘肃省自然科学基金项目(编号:22JR5RA588). （编号:22JR5RA588）
