{"title":"Eudesmane-guaiane sesquiterpenoid dimers from Aucklandia costus trigger paraptosis-like cell death via ROS accumulation and MAPK hyperactivation","authors":"","doi":"10.1016/S1875-5364(24)60592-3","DOIUrl":null,"url":null,"abstract":"<div><div>Three novel sesquiterpenoid heterodimers, designated as auckcostusolides A–C (<strong>1</strong>–<strong>3</strong>), were isolated from <em>Aucklandia costus</em> leaves. The structures of compounds <strong>1</strong>–<strong>3</strong> were elucidated through comprehensive spectroscopic analysis, with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism (ECD) calculations. Notably, compounds <strong>1</strong> and <strong>2</strong>, despite sharing identical planar structures derived from two identical sesquiterpenoids, exhibited opposite configurations at C-11 and C-8′. This configurational difference can be attributed to distinct Diels−Alder cycloaddition processes between the sesquiterpenoid monomers. Additionally, the cytotoxic effects of compounds <strong>1</strong>–<strong>3</strong> were evaluated against colorectal cancer HCT116 cells, fibrosarcoma HT1080 cells, and hepatocellular carcinoma HepG2 cells. Compounds <strong>1</strong>–<strong>3</strong> induced cell death was characterized by endoplasmic reticulum (ER) swelling and cytoplasmic vacuolization, typical morphological changes associated with paraptosis. Mechanistic studies revealed that compounds <strong>1</strong> and <strong>3</strong> triggered paraptosis-like cell death through the accumulation of reactive oxygen species (ROS), activation of ER stress, and stimulation of the MAPK signaling pathway.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Natural Medicines","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1875536424605923","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Three novel sesquiterpenoid heterodimers, designated as auckcostusolides A–C (1–3), were isolated from Aucklandia costus leaves. The structures of compounds 1–3 were elucidated through comprehensive spectroscopic analysis, with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism (ECD) calculations. Notably, compounds 1 and 2, despite sharing identical planar structures derived from two identical sesquiterpenoids, exhibited opposite configurations at C-11 and C-8′. This configurational difference can be attributed to distinct Diels−Alder cycloaddition processes between the sesquiterpenoid monomers. Additionally, the cytotoxic effects of compounds 1–3 were evaluated against colorectal cancer HCT116 cells, fibrosarcoma HT1080 cells, and hepatocellular carcinoma HepG2 cells. Compounds 1–3 induced cell death was characterized by endoplasmic reticulum (ER) swelling and cytoplasmic vacuolization, typical morphological changes associated with paraptosis. Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of reactive oxygen species (ROS), activation of ER stress, and stimulation of the MAPK signaling pathway.
期刊介绍:
The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM).
Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.