5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model

IF 4.8 3区化学 Q1 CHEMISTRY, MEDICINAL Natural Products and Bioprospecting Pub Date : 2024-07-02 DOI:10.1007/s13659-024-00462-y

Rui Ma, Xu-Yao Feng, Jiang-Jiang Tang, Wei Ha, Yan-Ping Shi

{"title":"5α-Epoxyalantolactone from Inula macrophylla attenuates cognitive deficits in scopolamine-induced Alzheimer’s disease mice model","authors":"Rui Ma, Xu-Yao Feng, Jiang-Jiang Tang, Wei Ha, Yan-Ping Shi","doi":"10.1007/s13659-024-00462-y","DOIUrl":null,"url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a complex neurodegenerative condition. 5<i>α</i>-epoxyalantolactone (5<i>α</i>-EAL), a eudesmane-type sesquiterpene isolated from the herb of <i>Inula macrophylla</i>, has various pharmacological effects. This work supposed to investigate the improved impact of 5<i>α</i>-EAL on cognitive impairment. 5<i>α</i>-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC<sub>50</sub> of 6.2 μM. 5<i>α</i>-EAL significantly reduced the production of prostaglandin E2 (PGE<sub>2</sub>) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5<i>α</i>-EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5<i>α</i>-EAL on cognitive impairment in vivo. After the mice were pretreated with 5<i>α</i>-EAL (10 and 30 mg/kg per day, <i>i.p.</i>) for 21 days, the behavioral experiments indicated that the administration of the 5<i>α</i>-EAL could alleviate the cognitive and memory impairments. 5<i>α</i>-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5<i>α</i>-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"14 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219692/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Natural Products and Bioprospecting","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13659-024-00462-y","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC₅₀ of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE₂) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile.

Graphical Abstract

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

从大叶桉树中提取的 5α-Epoxyalantolactone 可减轻东莨菪碱诱导的阿尔茨海默病小鼠模型的认知缺陷。

阿尔茨海默病（AD）是一种复杂的神经退行性疾病。5α-epoxyalantolactone (5α-EAL)是从大叶鸢尾科草本植物中分离出来的一种桉叶烷型倍半萜，具有多种药理作用。本研究旨在探讨 5α-EAL 对认知障碍的改善作用。5α-EAL 可抑制 BV-2 细胞在脂多糖（LPS）刺激下产生一氧化氮（NO），EC50 为 6.2 μM。5α-EAL 能明显减少前列腺素 E2（PGE2）和肿瘤坏死因子-α（TNF-α）的生成，同时还能抑制环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）蛋白的生成。5α-EAL穿透血脑屏障（BBB）的能力通过平行人工膜渗透试验得到了证实。采用东莨菪碱（SCOP）诱导的AD小鼠模型来评估5α-EAL对体内认知障碍的改善作用。小鼠经5α-EAL（每天10毫克和30毫克/千克，静脉注射）预处理21天后，行为实验表明5α-EAL能缓解认知和记忆障碍。5α-EAL能明显降低SCOP诱导的AD小鼠脑内的乙酰胆碱酯酶活性。总之，这些发现强调了天然产物5α-EAL作为一种潜在的生物活性化合物，因其药理特征而对减轻AD认知障碍的有益作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.