{"title":"石蒜碱通过抑制STING/NF-κB通路,减轻脂多糖诱导的Caco-2细胞炎症和肠上皮屏障功能障碍。","authors":"Weiwei Gao, Peng Guan, Wanpeng Gao, Xiaodan Li","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Lycorine (LYC) is an isoquinoline alkaloid known for its various biological effects like anti-viral and anti-inflammatory. The purpose of this research was to offer a reference for the clinical application of LYC in inflammatory bowel disease. The toxicity of LYC on Caco-2 cells was assessed utilizing CCK-8 assay and Lactate dehydrogenase (LDH) kit. Tunel staining and flow cytometry determined apoptosis and Elisa kits measured levels of inflammatory factors. Trans-endothelial electrical resistance (TEER) assay and FITC-dextran assay for Caco-2 cell permeability. Western blot assessed the levels of inflammation-related and stimulator of interferon genes (STING)/nuclear factor kappaB (NF-κB) pathway proteins. Caco-2 cell viability and LDH release were not impacted by LYC concentrations below 20μM and LYC (5, 10 and 20μM) attenuated inflammation and apoptosis in Caco-2 cells induced by lipopolysaccharide (LPS). LPS decreased TEER values and increased FITC-dextran levels and LYC ameliorated epithelial barrier dysfunction caused by LPS. LPS activated the STING/NF-κB pathway, which was hindered by LYC. The protective impact of LYC on Caco-2 cells was reduced by over expression STING. In conclusion, LYC reduced cell death and inflammation in Caco-2 cells and preserved the integrity of the epithelial barrier by hindering the STING/NF-κB pathway.</p>","PeriodicalId":19971,"journal":{"name":"Pakistan journal of pharmaceutical sciences","volume":"37 6","pages":"1443-1454"},"PeriodicalIF":0.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lycorine attenuates lipopolysaccharide-induced inflammation and intestinal epithelial barrier dysfunction in Caco-2 cells through inhibiting the STING/NF-κB pathway.\",\"authors\":\"Weiwei Gao, Peng Guan, Wanpeng Gao, Xiaodan Li\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Lycorine (LYC) is an isoquinoline alkaloid known for its various biological effects like anti-viral and anti-inflammatory. The purpose of this research was to offer a reference for the clinical application of LYC in inflammatory bowel disease. The toxicity of LYC on Caco-2 cells was assessed utilizing CCK-8 assay and Lactate dehydrogenase (LDH) kit. Tunel staining and flow cytometry determined apoptosis and Elisa kits measured levels of inflammatory factors. Trans-endothelial electrical resistance (TEER) assay and FITC-dextran assay for Caco-2 cell permeability. Western blot assessed the levels of inflammation-related and stimulator of interferon genes (STING)/nuclear factor kappaB (NF-κB) pathway proteins. Caco-2 cell viability and LDH release were not impacted by LYC concentrations below 20μM and LYC (5, 10 and 20μM) attenuated inflammation and apoptosis in Caco-2 cells induced by lipopolysaccharide (LPS). LPS decreased TEER values and increased FITC-dextran levels and LYC ameliorated epithelial barrier dysfunction caused by LPS. LPS activated the STING/NF-κB pathway, which was hindered by LYC. The protective impact of LYC on Caco-2 cells was reduced by over expression STING. In conclusion, LYC reduced cell death and inflammation in Caco-2 cells and preserved the integrity of the epithelial barrier by hindering the STING/NF-κB pathway.</p>\",\"PeriodicalId\":19971,\"journal\":{\"name\":\"Pakistan journal of pharmaceutical sciences\",\"volume\":\"37 6\",\"pages\":\"1443-1454\"},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pakistan journal of pharmaceutical sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pakistan journal of pharmaceutical sciences","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
石蒜碱(LYC)是一种异喹啉生物碱,因其多种生物作用而闻名,如抗病毒和抗炎。本研究旨在为LYC在炎症性肠病中的临床应用提供参考。采用CCK-8法和乳酸脱氢酶(LDH)试剂盒检测LYC对Caco-2细胞的毒性。隧道染色和流式细胞术检测细胞凋亡,Elisa试剂盒检测炎症因子水平。跨内皮电阻(TEER)法和fitc -葡聚糖法检测Caco-2细胞通透性。Western blot检测炎症相关和刺激干扰素基因(STING)/核因子κ b (NF-κB)通路蛋白水平。LYC浓度低于20μM时,Caco-2细胞活力和LDH释放不受影响,LYC(5、10和20μM)可减轻脂多糖(LPS)诱导的Caco-2细胞的炎症和凋亡。LPS降低TEER值,增加fitc -葡聚糖水平,LYC改善LPS引起的上皮屏障功能障碍。LPS激活了STING/NF-κB通路,而LYC抑制了这一通路。过表达STING可降低LYC对Caco-2细胞的保护作用。综上所述,LYC通过抑制STING/NF-κB通路,减少Caco-2细胞的细胞死亡和炎症,保持上皮屏障的完整性。
Lycorine attenuates lipopolysaccharide-induced inflammation and intestinal epithelial barrier dysfunction in Caco-2 cells through inhibiting the STING/NF-κB pathway.
Lycorine (LYC) is an isoquinoline alkaloid known for its various biological effects like anti-viral and anti-inflammatory. The purpose of this research was to offer a reference for the clinical application of LYC in inflammatory bowel disease. The toxicity of LYC on Caco-2 cells was assessed utilizing CCK-8 assay and Lactate dehydrogenase (LDH) kit. Tunel staining and flow cytometry determined apoptosis and Elisa kits measured levels of inflammatory factors. Trans-endothelial electrical resistance (TEER) assay and FITC-dextran assay for Caco-2 cell permeability. Western blot assessed the levels of inflammation-related and stimulator of interferon genes (STING)/nuclear factor kappaB (NF-κB) pathway proteins. Caco-2 cell viability and LDH release were not impacted by LYC concentrations below 20μM and LYC (5, 10 and 20μM) attenuated inflammation and apoptosis in Caco-2 cells induced by lipopolysaccharide (LPS). LPS decreased TEER values and increased FITC-dextran levels and LYC ameliorated epithelial barrier dysfunction caused by LPS. LPS activated the STING/NF-κB pathway, which was hindered by LYC. The protective impact of LYC on Caco-2 cells was reduced by over expression STING. In conclusion, LYC reduced cell death and inflammation in Caco-2 cells and preserved the integrity of the epithelial barrier by hindering the STING/NF-κB pathway.
期刊介绍:
Pakistan Journal of Pharmaceutical Sciences (PJPS) is a peer reviewed multi-disciplinary pharmaceutical sciences journal. The PJPS had its origin in 1988 from the Faculty of Pharmacy, University of Karachi as a biannual journal, frequency converted as quarterly in 2005, and now PJPS is being published as bi-monthly from January 2013.
PJPS covers Biological, Pharmaceutical and Medicinal Research (Drug Delivery, Pharmacy Management, Molecular Biology, Biochemical, Pharmacology, Pharmacokinetics, Phytochemical, Bio-analytical, Therapeutics, Biotechnology and research on nano particles.