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羽扇豆醇的抗炎作用及其作为新药开发候选物的研究

Anti-Inflammatory Effects of Lupeol as a Candidate for New Drug Development.

机构信息

College of Pharmacy, CMRI Research Institute of Pharmaceutical Sciences, Kyungpook, National University, Daegu 41566, Republic of Korea.

Department of Ophthalmology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.

出版信息

Am J Chin Med. 2024;52(6):1759-1771. doi: 10.1142/S0192415X2450068X. Epub 2024 Sep 26.

Abstract

This study explores the anti-inflammatory properties of lupeol, a notable phytosterol found in various medicinal plants, highlighting its potential as a candidate for new drug development. We examined the effects of lupeol on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), as well as its impact on inflammatory markers in the lung tissues of LPS-challenged mice. Lupeol treatment enhanced HO-1 production, inhibited nuclear factor (NF)-κB activity, and reduced levels of COX-2/prostaglandin E2 (PGE2) and iNOS/nitric oxide (NO). In addition, lupeol decreased the phosphorylation of signal transducer and activator of transcription 1 (STAT-1) and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), enhancing its binding to the anti-oxidant response element (ARE) and subsequently reducing interleukin (IL)-1β expression. , lupeol significantly lowered iNOS expression and tumor necrosis factor (TNF)-α levels in bronchoalveolar lavage fluid from LPS-treated mice. These findings suggest that lupeol exerts its anti-inflammatory effects by modulating key signaling pathways, positioning it as a promising candidate for the development of novel therapeutics targeting pathological inflammation.

摘要

本研究探讨了羽扇豆醇的抗炎特性,羽扇豆醇是一种存在于多种药用植物中的重要植物甾醇,具有成为新药开发候选物的潜力。我们研究了羽扇豆醇对脂多糖(LPS)刺激的人脐静脉内皮细胞(HUVEC)中血红素加氧酶(HO)-1、环氧化酶(COX)-2和诱导型一氧化氮合酶(iNOS)的影响,以及其对 LPS 挑战的小鼠肺组织中炎症标志物的影响。羽扇豆醇处理增强了 HO-1 的产生,抑制了核因子(NF)-κB 的活性,并降低了 COX-2/前列腺素 E2(PGE2)和 iNOS/一氧化氮(NO)的水平。此外,羽扇醇降低了信号转导和转录激活因子 1(STAT-1)的磷酸化,并促进了核红细胞相关因子 2(Nrf2)的核易位,增强了其与抗氧化反应元件(ARE)的结合,从而降低了白细胞介素(IL)-1β的表达。羽扇醇还显著降低了 LPS 处理小鼠支气管肺泡灌洗液中的 iNOS 表达和肿瘤坏死因子(TNF)-α水平。这些发现表明,羽扇豆醇通过调节关键信号通路发挥其抗炎作用,使其成为针对病理性炎症的新型治疗药物开发的有前途的候选物。

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