Shanmugasundaram Nirenjen, Jayasankar Narayanan
Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology (SRMIST), Kattankulathur, Chengalpattu, 603203, Tamil Nadu, India.
Curr Drug Discov Technol. 2025;22(2):e15701638332872. doi: 10.2174/0115701638332872240922184903.
Diabetic wound healing poses a significant challenge due to the intricate disruptions in cellular and molecular processes induced by hyperglycaemia, leading to delayed or impaired tissue repair. Computational techniques offer a promising avenue for unravelling the complexities of diabetic wound healing by elucidating the molecular mechanisms involved.
This study utilized molecular docking and dynamics simulations to explore the potential therapeutic effectiveness of olivetol, a phenolic compound, in the context of diabetic wound healing. Furthermore, computational methodologies, encompassing pkCSM, Swiss ADME, OSIRIS® property explorer, PASS online web resource, and MOLINSPIRATION® software, were employed to forecast the pharmacokinetic properties, biological actions, and in vitro analyses, such as MTT and scratch assays, to evaluate the therapeutic effectiveness of olivetol in wound healing.
Our findings have revealed olivetol to be a promising candidate for targeting multiple pathways implicated in diabetic wound healing. Its ability to modulate inflammation, oxidative stress, extracellular matrix remodeling, angiogenesis, and cell signaling suggests a multifaceted approach to promoting effective wound repair. Moreover, olivetol has been found to demonstrate strong binding affinity with key MRSA target proteins, indicating its potential as an antimicrobial agent against MRSA infections in diabetic wounds. The MTT assay demonstrated cell viability with an IC value of 40.80 μM, highlighting its cytotoxicity potential. Additionally, the scratch assay confirmed promising wound healing activity, showcasing its effectiveness in promoting cell migration and closure.
Olivetol emerges as a promising candidate for targeted interventions in non-healing diabetic wounds, particularly due to its ability to address prolonged inflammation, a common obstacle in diabetic wound healing.
由于高血糖引起的细胞和分子过程的复杂紊乱，糖尿病伤口愈合面临重大挑战，导致组织修复延迟或受损。计算技术为通过阐明相关分子机制来揭示糖尿病伤口愈合的复杂性提供了一条有前景的途径。
本研究利用分子对接和动力学模拟来探索酚类化合物橄榄醇在糖尿病伤口愈合背景下的潜在治疗效果。此外，采用了包括pkCSM、Swiss ADME、OSIRIS®性质探索器、PASS在线网络资源和MOLINSPIRATION®软件在内的计算方法来预测药代动力学性质、生物学作用，并进行体外分析，如MTT和划痕试验，以评估橄榄醇在伤口愈合中的治疗效果。
我们的研究结果表明，橄榄醇是靶向参与糖尿病伤口愈合的多种途径的有前景的候选物。它调节炎症、氧化应激、细胞外基质重塑、血管生成和细胞信号传导的能力表明其采用多方面方法促进有效伤口修复。此外，已发现橄榄醇与关键的耐甲氧西林金黄色葡萄球菌（MRSA）靶蛋白具有很强的结合亲和力，表明其作为抗糖尿病伤口中MRSA感染的抗菌剂的潜力。MTT试验显示细胞活力，IC值为40.80 μM，突出了其潜在的细胞毒性。此外，划痕试验证实了其有前景的伤口愈合活性，展示了其在促进细胞迁移和伤口闭合方面的有效性。
橄榄醇成为非愈合性糖尿病伤口靶向干预的有前景的候选物，特别是因为它能够解决长期炎症问题，而长期炎症是糖尿病伤口愈合中的常见障碍。
