Molecular docking and in vitro evaluation of glucosamine sulfate targeting MMP-3, MMP-9, and IL-4 for potential osteoarthritis treatment.

Q2 Pharmacology, Toxicology and Pharmaceutics

Drug metabolism and personalized therapy Pub Date : 2024-12-19 DOI:10.1515/dmpt-2024-0067

Venkataramanan Srinivasan, Selvaraj Kunjiappan, Ponnusamy Palanisamy

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引用次数: 0

Abstract

Objectives: This study intended to investigate the potential of glucosamine sulfate (GS) as an inhibitor of genes involved in osteoarthritis (OA) development. Despite GS is often used for OA treatment due to its cartilage preservation and minimum side effects, the molecular mechanism behind its interactions remains unknown.

Methods: Molecular docking was conducted to analyze the interactions between glucosamine sulfate and genes associated with OA such as matrix metalloproteinase-3 (MMP-3), MMP-9, and interleukin-4 (IL-4). Additionally, a cell viability assay using RAW 264.7 cells was performed to evaluate the toxicity of glucosamine sulfate at various concentrations.

Results: Molecular docking results revealed that glucosamine sulfate has a good binding affinity and stable interactions with MMP-3, MMP-9, and IL-4, indicating that it may have inhibitory effects on targeted genes. Nevertheless, the cell viability assay analysis demonstrated that glucosamine sulfate had considerable toxic effects in RAW 264.7 cells at highest concentrations.

Conclusions: Glucosamine sulfate exhibited stable molecular interactions with genes associated to OA development. However, GS toxicity at high concentrations necessitates future research studies to optimize dosing and assess its therapeutic safety in OA treatment.

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靶向MMP-3、MMP-9和IL-4治疗骨关节炎的硫酸氨基葡萄糖分子对接及体外评价

目的：本研究旨在探讨硫酸氨基葡萄糖（GS）作为骨关节炎（OA）发展相关基因抑制剂的潜力。尽管GS因其软骨保存和最小的副作用而常用于OA治疗，但其相互作用背后的分子机制尚不清楚。方法：通过分子对接分析硫酸氨基葡萄糖与OA相关基因基质金属蛋白酶-3 （MMP-3）、MMP-9、白细胞介素-4 （IL-4）的相互作用。此外，使用RAW 264.7 细胞进行细胞活力测定，以评估不同浓度硫酸氨基葡萄糖的毒性。结果：分子对接结果显示，硫酸氨基葡萄糖与MMP-3、MMP-9、IL-4具有良好的结合亲和力和稳定的相互作用，提示其可能对靶基因有抑制作用。然而，细胞活力分析表明，在最高浓度下，硫酸氨基葡萄糖对RAW 264.7 细胞具有相当大的毒性作用。结论：硫酸氨基葡萄糖与骨性关节炎相关基因表现出稳定的分子相互作用。然而，GS在高浓度下的毒性需要进一步的研究来优化剂量和评估其在OA治疗中的治疗安全性。

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

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.