Department of Orthopedic Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Bioengineered. 2022 Jun;13(6):14438-14449. doi: 10.1080/21655979.2022.2086379.
saponins (PNS) have been reported to have good anti-inflammatory effects. However, the anti-inflammatory effect mechanism in rheumatoid arthritis (RA) remains unknown. The focus of this research was to investigate the molecular mechanism of PNS in the treatment of RA. The primary active components of PNS were tested utilizing the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform based on oral bioavailability and drug-likeness. The target databases for knee osteoarthritis were created using GeneCards and Online Mendelian Inheritance in Man (OMIM). The visual interactive network structure 'active component - action target - illness' was created using Cytoscape software. A protein interaction network was built, and associated protein interactions were analyzed using the STRING database. The key targets were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analyses. The effects of PNS on cell growth were studied in human umbilical vein endothelial cells (HUVECs) treated with various doses of PNS, and the optimum concentration of PNS was identified. PNS was studied for its implication on angiogenesis and migration. The active components of PNS had 114 common targets, including cell metabolism and apoptosis, according to the network analysis. The therapeutic effects of the PNS components were suggested to be mediated through apoptotic and cytokine signaling pathways. In vitro, PNS therapy boosted HUVEC proliferation. Wound healing, Boyden chamber and tube formation tests suggested that PNS may increase HUVEC activity and capillary-like tube branching. This study clarified that for the treatment of RA, PNS has multisystem, multicomponent, and multitargeted properties.
皂苷（PNS）已被报道具有良好的抗炎作用。然而，其在类风湿关节炎（RA）中的抗炎作用机制尚不清楚。本研究的重点是探讨 PNS 治疗 RA 的分子机制。利用中药系统药理学数据库（TCMSP）和基于口服生物利用度和类药性的分析平台，测试了 PNS 的主要活性成分。利用 GeneCards 和在线孟德尔遗传（OMIM）创建了膝骨关节炎的目标数据库。使用 Cytoscape 软件创建了“活性成分-作用靶点-疾病”可视化互作网络结构。利用 STRING 数据库构建了蛋白质相互作用网络，并分析了相关蛋白的相互作用。利用京都基因与基因组百科全书（KEGG）通路和基因本体论（GO）生物过程富集分析对关键靶点进行分析。研究了 PNS 对人脐静脉内皮细胞（HUVEC）的生长影响，用不同剂量的 PNS 处理 HUVEC，确定了 PNS 的最佳浓度。研究了 PNS 对血管生成和迁移的影响。根据网络分析，PNS 的活性成分有 114 个共同靶点，包括细胞代谢和细胞凋亡。PNS 成分的治疗效果可能通过细胞凋亡和细胞因子信号通路介导。体外实验表明，PNS 治疗可促进 HUVEC 增殖。划痕愈合、Boyden 室和管形成试验表明，PNS 可能增加 HUVEC 活性和毛细血管样管分支。本研究阐明了 PNS 具有多系统、多成分和多靶点的特性，可用于治疗 RA。
