Structural Modification of Alepterolic Acid to Discover New Anti-Inflammatory Agents

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

Archiv der Pharmazie Pub Date : 2026-09-22 DOI:10.1002/ardp.70338

Yating Jia, Yanchun Sun, Xiaoran Min, Peixin Wang, Nigora Rustamova, Chaoyuan Liu, Yaru Cheng, Jianguo Cao, Jingzhe Pu, Guozheng Huang

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Abstract

Alepterolic acid is a natural compound occurring in Aleuritopteris argentea (Gmél.) Fée. In this study, 12 derivatives of alepterolic acid were obtained by chemical modification and evaluated regarding their effects on nitric oxide (NO) production in RAW264.7 macrophages stimulated by lipopolysaccharide (LPS). Notably, compound 13 exhibited low toxicity while significantly inhibiting LPS-induced NO production. To elucidate its immunomodulatory mechanism, we quantified transcription levels of key cellular inflammatory factors (TNF-α and IL-6) using RT-qPCR and measured protein levels of key cellular inflammatory factor (iNOS) by Western blotting. Additionally, mitochondrial membrane potential and concentrations of reactive oxygen species (ROS) in RAW264.7 cells were analyzed by flow cytometry, and the phosphorylation status of key proteins in the MAPK inflammatory pathway was assessed by Western blotting. The results demonstrate that compound 13 exerts its anti-inflammatory effects by inhibiting MAPK pathway phosphorylation, downregulating LPS-induced transcription of proinflammatory cytokines (TNF-α, IL-6), reducing ROS generation, and delaying the decline of mitochondrial membrane potential. This study provides a basis for the application of alepterolic derivatives in inflammatory diseases.

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烯醛酸结构修饰发现新型抗炎药。

阿勒霉酸是一种天然化合物，存在于阿勒霉属植物中。费。本研究通过化学修饰获得了12种乙酰萘酚酸衍生物，并评价了它们对脂多糖（LPS）刺激RAW264.7巨噬细胞产生一氧化氮（NO）的影响。值得注意的是，化合物13表现出低毒性，同时显著抑制lps诱导的NO产生。为了阐明其免疫调节机制，我们采用RT-qPCR定量了关键细胞炎症因子（TNF-α和IL-6）的转录水平，并采用Western blotting检测了关键细胞炎症因子（iNOS）的蛋白水平。此外，流式细胞术分析RAW264.7细胞线粒体膜电位和活性氧（ROS）浓度，Western blotting检测MAPK炎症通路关键蛋白的磷酸化状态。结果表明，化合物13通过抑制MAPK通路磷酸化、下调lps诱导的促炎细胞因子（TNF-α、IL-6）转录、减少ROS生成、延缓线粒体膜电位下降发挥抗炎作用。本研究为阿霉素衍生物在炎性疾病中的应用提供了依据。

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

Archiv der Pharmazie 医学-化学综合

CiteScore

7.90

自引率

5.90%

发文量

176

审稿时长

3.0 months

期刊介绍： Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.