Xu Zhouhengte, Su Pingping, Zhou Xiahui, Zheng Zhihui, Zhu Yibo, Wang Qinglai
Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, China.
The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Front Med (Lausanne). 2024 Oct 18;11:1422306. doi: 10.3389/fmed.2024.1422306. eCollection 2024.
Osteoarthritis (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.
This 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.
Bioinformatic 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.
Network pharmacology analysis identified an MSMP component-target-pathway network comprising 11 central active compounds, 25 gene targets, and 12 biological pathways.
These findings imply that the therapeutic effects of MSMP was potentially mediated by targeting several pivotal genes, such as androgen receptor (), , and , 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.
The 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.
骨关节炎（OA）是最常见的关节炎形式，也是成年人主要的肌肉骨骼疾病。改良四妙散（MSMP）已被广泛用于治疗OA，临床疗效显著。
由于MSMP的作用模式尚不清楚，本研究旨在通过网络药理学、分子对接和分子动力学模拟阐明其在OA中的潜在作用机制。
采用生物信息学分析评估MSMP的主要化学成分，确定潜在的靶基因，并筛选与OA相关的基因。然后应用网络药理学方法确定MSMP在OA治疗中的关键靶基因。进一步的分析包括基因本体论（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证实了相关通路中的这些关键靶点。
网络药理学分析确定了一个由11种核心活性化合物、25个基因靶点和12条生物学通路组成的MSMP成分-靶点-通路网络。
这些发现表明，MSMP的治疗作用可能是通过靶向几个关键基因，如雄激素受体（）、、和，以及调节一些通路，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来介导的。分子对接评估表明，MSMP的这些化合物，如小檗碱、山柰酚、槲皮素和木犀草素，对AR和AKT1具有高结合亲和力。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。
MSMP的治疗作用可能归因于其活性成分如小檗碱、山柰酚、木犀草素和槲皮素对多种通路的调节，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。特别是，它们对AR和AKT1等靶基因的作用有助于MSMP在OA治疗中观察到的治疗效果。
