基于网络药理学和实验验证的藏药十味乳香散治疗急性痛风性关节炎分子机制探究

Molecular Mechanism of Tibetan Medicine Shiwei Ruxiang San Powder in the Treatment of Acute Gouty Arthritis Based on Network Pharmacology and Experimental Verification

目的:探讨藏药十味乳香散(SWRXS)治疗急性痛风性关节炎(Acute Gouty Arthritis,AGA)的作用机制。方法:利用TCMSP、CNKI及PubMed查阅文献收集药物的化学成分,借助化源网、PubChem、SwissADME、SwissTargetPrediction及Cytoscape筛选SWRXS的靶点及核心活性成分;依托Drugbank、OMIM、GeneCards疾病数据库收集AGA的相关靶点。将SWRXS及AGA交集靶点进行拓扑分析,筛选核心靶点;使用Metascape进行GO和KEGG富集分析,微生信可视化。建立AGA大鼠模型,观察SWRXS对AGA大鼠关节肿胀度、步态、血清炎症因子IL-1β、TNF-α、滑膜组织病理形态的影响,进一步验证其作用机制。结果:通过网络药理学分析发现,SWRXS的核心成分主要包括槲皮素、山柰酚、木犀草素、鞣花酸、异鼠李素等,核心靶点包括TNF、IL6、PTGS2、SRC、IL1B等,核心通路包括NF-κB、TLRs、JAK-STAT、PI3K-Akt等。动物实验结果显示,SWRXS可以减轻AGA模型大鼠的关节肿胀程度,降低大鼠血中炎症因子TNF-α、IL-1β的含量,使滑膜细胞增生及炎症细胞浸润均明显减轻。结论:十味乳香散通过多种化合物作用于多个通路、多个靶点发挥其对AGA的治疗作用,其中活性成分槲皮素、山奈酚、木犀草素等可能通过作用于TNF、IL1B等靶点,进而通过NF-κB、TLRs、JAK-STAT、PI3K-Akt等信号通路产生抑制炎症反应、减弱氧化应激反应、增加嘌呤化合物代谢和抑制破骨细胞过度增殖等方面的分子效应。

Objective To explore the mechanism of Tibetan medicine Shiwei Ruxiang San(SWRXS)poeder treating Acute Gouty Arthritis(AGA).Methods TCMSP,CNKI and PubMed were used to collect the chemical components of drugs,and the target and core active components of SWRXS were screened by Huayuan,PubChem,SwissADME,SwissTargetPrediction and Cytoscape.Collect the related targets of AGA based on Drugbank,OMIM and GeneCards disease databases.Topological analysis of SWRXS and AGA intersection targets is carried out to screen the core targets,Metascape was used for enrichment analysis of GO and KEGG,and micro-generation information was visualized.To establish AGA rat model,observe the effects of SWRXS on joint swelling,gait,serum inflammatory factors IL-1β,TNF-αand synovial tissue pathological morphology of AGA rats,and further verify its mechanism.Results Through the analysis of network pharmacology,it was found that the core components of SWRXS mainly included quercetin,kaempferol,luteolin,ellagic acid,isorhamnetin,etc.,the core targets included TNF,IL6,PTGS2,SRC,IL1B,etc.,and the core pathways included NF-κB,TLRs,JAK-STAT,PI3K-Akt,etc.The results of animal experiments show that SWRXS can reduce the degree of joint swelling in AGA model rats,reduce the contents of inflammatory factors TNF-αand IL-1βin blood of rats,and significantly reduce synovial cell proliferation and inflammatory cell infiltration.Conclusion SWRXS exerts its therapeutic effect on AGA through multiple compounds acting on multiple pathways and multiple targets,among which quercetin,kaempferol,luteolin and other active components may act on TNF,IL1B and other targets,and then produce molecular effects such as inhibiting inflammatory response,weakening oxidative stress response,increasing purine compound metabolism and inhibiting osteoclasts excessive proliferation through signal pathways such as NF-κB,TLRs,JAK-STAT and PI3K-Akt.