Bioactive Compound Chemistry and Antiasthmatic Activity of Betulinic Acid and Taraxerol in Experimental Models.

IF 2.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Current topics in medicinal chemistry Pub Date : 2025-04-30 DOI:10.2174/0115680266358488250421012523

Shiv Narayan, Gaurav Krishna, Raghav Mishra

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引用次数: 0

Abstract

Background: The natural molecules betulinic acid (BA) and taraxerol (T) have many biological and therapeutic uses, one of which is the relief from asthma symptoms. This study wasThis study aimed to assess BA and T effectiveness in treating bronchial asthma and perform a molecular docking study to find the binding energy of BA and T with β-adrenoceptor.

Methods: Using ethanol as the solvent, the Bacopa monnieri leaves were extracted using a soxhlet equipment. As a reference medicine, budesenoid was utilised. With PyRx 0.8, the molecular docking experiment was conducted using AutoDock vina. The protocol followed by the acute toxicity study was the OECD guideline 425. The effectiveness of the test medication in alleviating asthma was determined using an anaphylactic microshock model in guinea pigs.

Results: Molecular docking analysis showed high binding affinities of BA (-7.95 kcal/mol) and T (-8.23 kcal/mol) to LOX-5, which could suppress the synthesis of leukotriene, one of the central mediators of asthma pathogenesis. In vivo study, the BA and T treatment prolonged pre-convulsion time in guinea pigs up to 506.66 seconds as compared with the control (406.6 seconds, p < 0.05). This suggests protection against bronchial hyperresponsiveness. ELISA assays demonstrated that BA and T decreased the levels of TNF-α and increased IL-10, indicating a potential modulation of inflammation (p < 0.05). Markers of oxidative stress were lowered in treated animals, as demonstrated by the lowered MDA and enhanced activities of antioxidant enzymes such as SOD, CAT, and GSH, suggesting a protective effect against oxidative lung damage (p < 0.05). Histological analysis confirmed a decrease in inflammatory cell infiltration and airway remodeling in the treated groups compared to the OVA-induced controls.

Conclusion: The results of the animal studies showed that BA and T reduced anaphylaxis, suggesting that it could be a viable alternative to current asthma treatments in the future. The results of the molecular docking investigation, however, showed that BA and T may indeed bind to the target receptor, opening the door to new treatment possibilities.

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实验模型中白桦酸和Taraxerol的生物活性化合物化学及平喘活性。

背景：天然分子白桦酸（BA）和taraxerol (T)具有许多生物学和治疗用途，其中之一是缓解哮喘症状。本研究旨在评估BA和T治疗支气管哮喘的有效性，并进行分子对接研究，寻找BA和T与β-肾上腺素受体的结合能。方法：采用索氏提取装置，以乙醇为溶剂提取假马齿苋叶。以布地仙素为对照药。使用PyRx 0.8软件，使用AutoDock vina进行分子对接实验。急性毒性研究遵循的方案是经合组织准则425。用豚鼠过敏性微休克模型测定试验药物缓解哮喘的有效性。结果：分子对接分析显示BA （-7.95 kcal/mol）和T （-8.23 kcal/mol）对LOX-5具有较高的结合亲和力，可抑制哮喘发病的中心介质之一白三烯的合成。体内实验结果显示，与对照组相比，BA和T处理可使豚鼠惊厥前时间延长506.66 s （406.6 s, p < 0.05）。这表明对支气管高反应性有保护作用。ELISA检测显示，BA和T可降低TNF-α水平，升高IL-10水平，提示其可能调节炎症（p < 0.05）。氧化应激标志物降低，MDA降低，SOD、CAT、GSH等抗氧化酶活性增强，提示对氧化性肺损伤有保护作用（p < 0.05）。组织学分析证实，与ova诱导的对照组相比，治疗组炎症细胞浸润和气道重塑减少。结论：动物实验结果表明，BA和T可减少过敏反应，提示其可能是未来哮喘治疗的可行替代方案。然而，分子对接研究的结果表明，BA和T确实可能与靶受体结合，为新的治疗可能性打开了大门。

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

Current topics in medicinal chemistry 医学-医药化学

CiteScore

6.40

自引率

2.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.