Table_8_Exploring the mechanism of action of Modified Simiao Powder in the treatment of osteoarthritis: an in-silico study.XLSX

IntroductionOsteoarthritis (OA) is the most common form of arthritis and the leading musculoskeletal disorders in adults. Modified Simiao Powder (MSMP) has been widely used in the treatment of OA with remarkable clinical ecaciousness.ObjectiveThis study aimed to elucidate underlying mechanisms of MSMP in OA by employing network pharmacology, molecular docking, and molecular dynamics simulations, due to the unclear mode of action.MethodsBioinformatic analysis was used to evaluate the major chemical constituents of MSMP, determine prospective target genes, and screen genes associated with OA. Network pharmacology methods were then applied to identify the crucial target genes of MSMP in OA treatment. Further analyses included gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. These key targets within the pertinent pathways was further confirmed by molecular docking, binding energy evaluation, and molecular dynamics simulations.ResultsNetwork pharmacology analysis identified an MSMP component–target–pathway network comprising 11 central active compounds, 25 gene targets, and 12 biological pathways.DiscussionThese findings imply that the therapeutic effects of MSMP was potentially mediated by targeting several pivotal genes, such as androgen receptor (AR), NFKB1, AKT1, MAPK1, and CASP3, and regulating some pathways, including lipid metabolism and atherosclerosis, the AGE–RAGE signaling pathway in diabetic complications, the PI3K–Akt signaling pathway, fluid shear stress, atherosclerosis, and Kaposi's sarcoma-associated herpesvirus infection. Molecular docking assessments demonstrated that these compounds of MSMP, such as berberine, kaempferol, quercetin, and luteolin, exhibit high binding anities to AR and AKT1. Molecular dynamics simulations validated the interactions between these compounds and targets.ConclusionThe therapeutic effect of MSMP likely attributed to the modulation of multiple pathways, including lipid metabolism, atherosclerosis, the AGE-RAGE signaling pathway, and the PI3K-Akt signaling pathway, by the active components such as berberine, kaempferol, luteolin, and quercetin. Especially, their actions on target genes like AR and AKT1 contribute to the therapeutic benefits of MSMP observed in the treatment of OA.

引言：骨关节炎（OA）是成年人中最常见的关节炎，也是主要的骨骼肌肉疾病。改良的沈药散（MSMP）在OA的治疗中已被广泛应用，并展现出显著的临床疗效。研究目的：本研究的目的是通过运用网络药理学、分子对接以及分子动力学模拟等方法，阐明MSMP在OA中的潜在作用机制，鉴于其作用机理尚不明确。研究方法：利用生物信息学分析评估MSMP的主要化学成分，确定潜在靶基因，并筛选与OA相关的基因。随后，应用网络药理学方法以识别MSMP在OA治疗中的关键靶基因。进一步的分析包括基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集。通过分子对接、结合能评估和分子动力学模拟进一步验证了相关通路中的关键靶点。研究结果：网络药理学分析确定了一个由11个核心活性化合物、25个基因靶点和12个生物通路组成的MSMP成分-靶点-通路网络。讨论：这些发现表明，MSMP的治疗效果可能通过靶向多个关键基因，例如雄激素受体（AR）、NFKB1、AKT1、MAPK1和CASP3，以及调节某些通路，包括脂质代谢和动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、PI3K-Akt信号通路、流体剪切应力、动脉粥样硬化和卡波西肉瘤相关疱疹病毒感染等途径来实现。分子对接评估显示，MSMP中的这些化合物，如黄连素、山奈酚、槲皮素和木犀草素，对AR和AKT1具有较高的结合亲和力。分子动力学模拟验证了这些化合物与靶点之间的相互作用。结论：MSMP的治疗效果可能归因于其活性成分如黄连素、山奈酚、木犀草素和槲皮素对多个通路（包括脂质代谢、动脉粥样硬化、AGE-RAGE信号通路和PI3K-Akt信号通路）的调节作用。特别是，它们对靶基因如AR和AKT1的作用有助于MSMP在OA治疗中观察到的治疗效果。