Combining Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and Experimental Validation to Uncover the Efficacy and Mechanisms of Si-Miao-Yong-An Decoction in Diabetic Wound Healing.

IF 4.2 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S506739
Shujuan Zhang, Yiming Shao, Ranran Jin, Baodong Ma
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Abstract

Purpose: Si-Miao-Yong-An (SMYA) Decoction, a traditional Chinese herbal mixture, shows promise for managing diabetic complications. Up to this point, no reports have explored the effects of SMYA on diabetic wounds or the underlying mechanisms. This study aimed to investigate the therapeutic potential of SMYA in promoting diabetic wound healing and to elucidate the underlying molecular mechanisms.

Methods: The wound healing effects of SMYA were evaluated in db/db diabetic mice by measuring wound closure rates and histological characteristics, including epidermal thickness and collagen deposition. Network pharmacology was utilized to identify active ingredients and corresponding therapeutic targets of SMYA, followed by validation through molecular docking and molecular dynamics simulations. KEGG and GO enrichment analyses were conducted to elucidate the relevant biological processes and pathways. In vitro studies involving high-glucose-treated HUVECs assessed the effects of SMYA-containing serum on cellular migration and angiogenesis. Finally, the expression of inflammatory factors and RAGE in the wound tissue was detected by qRT-PCR.

Results: SMYA significantly accelerated wound closure in db/db mice, as evidenced by improved epidermal thickness, tissue morphology, and collagen deposition. Network pharmacology identified 140 overlapping genes involved in angiogenesis and inflammation, with the AGE-RAGE signaling pathway playing a central role. Molecular docking and dynamics simulations revealed strong binding stability of quercetin and kaempferol to inflammation-related hub targets, including IL-6, TNF, and IL-1β. In vitro, SMYA-containing serum alleviated high-glucose-induced impairments in HUVEC migration and angiogenesis. Furthermore, qRT-PCR analysis showed that SMYA significantly downregulated Tnf, Il1b, Il6, and Rage expression in wound tissues, supporting its anti-inflammatory effect.

Conclusion: SMYA promotes diabetic wound healing by modulating the inflammatory microenvironment and inhibiting the AGE-RAGE signaling pathway. These findings provide robust evidence for SMYA's therapeutic potential and lay a foundation for its future clinical application in treating diabetic wounds.

目的:四妙勇安(SMYA)煎剂是一种传统的中草药混合物,有望控制糖尿病并发症。到目前为止,还没有任何报道探讨四妙汤对糖尿病伤口的影响或其潜在机制。本研究旨在探讨 SMYA 在促进糖尿病伤口愈合方面的治疗潜力,并阐明其潜在的分子机制:方法:通过测量伤口闭合率和组织学特征(包括表皮厚度和胶原沉积),评估了 SMYA 对 db/db 糖尿病小鼠伤口愈合的影响。利用网络药理学确定了SMYA的活性成分和相应的治疗靶点,然后通过分子对接和分子动力学模拟进行了验证。还进行了 KEGG 和 GO 富集分析,以阐明相关的生物过程和途径。涉及高葡萄糖处理的 HUVECs 的体外研究评估了含 SMYA 血清对细胞迁移和血管生成的影响。最后,通过 qRT-PCR 检测了伤口组织中炎性因子和 RAGE 的表达:结果:SMYA明显加速了db/db小鼠伤口的愈合,表皮厚度、组织形态和胶原沉积都得到了改善。网络药理学发现了 140 个涉及血管生成和炎症的重叠基因,其中 AGE-RAGE 信号通路起着核心作用。分子对接和动力学模拟显示,槲皮素和山奈酚与炎症相关枢纽靶点(包括IL-6、TNF和IL-1β)的结合稳定性很强。在体外,含 SMYA 的血清减轻了高葡萄糖诱导的 HUVEC 迁移和血管生成障碍。此外,qRT-PCR分析表明,SMYA能显著下调伤口组织中Tnf、Il1b、Il6和Rage的表达,支持其抗炎作用:结论:SMYA 通过调节炎症微环境和抑制 AGE-RAGE 信号通路促进糖尿病伤口愈合。这些发现为 SMYA 的治疗潜力提供了有力的证据,并为其未来在治疗糖尿病伤口方面的临床应用奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
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