2-杰拉尔基-1-甲氧基赤藓霉素II通过AMPK激活和AKT抑制减轻肝细胞中的脂质积聚和炎症。

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL Archives of Pharmacal Research Pub Date : 2023-10-02 DOI:10.1007/s12272-023-01464-z
Yiyuan Xi, Soeun Kim, Thi Thanh Thuy Nguyen, Phil Jun Lee, Jujia Zheng, Zhuofeng Lin, Namki Cho
{"title":"2-杰拉尔基-1-甲氧基赤藓霉素II通过AMPK激活和AKT抑制减轻肝细胞中的脂质积聚和炎症。","authors":"Yiyuan Xi,&nbsp;Soeun Kim,&nbsp;Thi Thanh Thuy Nguyen,&nbsp;Phil Jun Lee,&nbsp;Jujia Zheng,&nbsp;Zhuofeng Lin,&nbsp;Namki Cho","doi":"10.1007/s12272-023-01464-z","DOIUrl":null,"url":null,"abstract":"<div><p>A growing proportion of the global adult and pediatric populations are currently affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from <i>Lespedeza bicolor</i>, could alleviate lipid accumulation and inflammatory responses in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid accumulation and attenuated inflammatory responses without cytotoxicity. Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), and activates PPARα by activating AMP-activated kinase (AMPK), leading to the alleviation of lipid accumulation. In addition, GMET suppresses the NF-κB pathway by activating AMPK and inhibiting the activated protein kinase B (AKT)/IκB-kinase (IKK) pathway, leading to the inhibition of the inflammatory response in hepatocytes. All these protective effects of GMET on lipid accumulation and inflammation in vivo and in vitro were largely abolished by co-treatment with dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid accumulation and inflammation to preserve normal hepatocyte function in steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to improve steatohepatitis.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 9-10","pages":"808 - 824"},"PeriodicalIF":6.9000,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition\",\"authors\":\"Yiyuan Xi,&nbsp;Soeun Kim,&nbsp;Thi Thanh Thuy Nguyen,&nbsp;Phil Jun Lee,&nbsp;Jujia Zheng,&nbsp;Zhuofeng Lin,&nbsp;Namki Cho\",\"doi\":\"10.1007/s12272-023-01464-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>A growing proportion of the global adult and pediatric populations are currently affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from <i>Lespedeza bicolor</i>, could alleviate lipid accumulation and inflammatory responses in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid accumulation and attenuated inflammatory responses without cytotoxicity. Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), and activates PPARα by activating AMP-activated kinase (AMPK), leading to the alleviation of lipid accumulation. In addition, GMET suppresses the NF-κB pathway by activating AMPK and inhibiting the activated protein kinase B (AKT)/IκB-kinase (IKK) pathway, leading to the inhibition of the inflammatory response in hepatocytes. All these protective effects of GMET on lipid accumulation and inflammation in vivo and in vitro were largely abolished by co-treatment with dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid accumulation and inflammation to preserve normal hepatocyte function in steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to improve steatohepatitis.</p></div>\",\"PeriodicalId\":8287,\"journal\":{\"name\":\"Archives of Pharmacal Research\",\"volume\":\"46 9-10\",\"pages\":\"808 - 824\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2023-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Pharmacal Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12272-023-01464-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Pharmacal Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12272-023-01464-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

摘要

目前,全球越来越多的成人和儿童人群受到非酒精性脂肪性肝炎(NASH)的影响,导致在没有有效药物治疗的情况下肝纤维化和肝细胞癌的发病率上升。在这里,我们研究了从双色胡枝子中分离的2-香叶基-1-甲氧基赤藓霉素II(GMET)是否可以缓解NASH模型中的脂质积聚和炎症反应。GMET在体外和体内表现出强大的抗脂质积聚作用,并在没有细胞毒性的情况下减弱炎症反应。从机制上讲,GMET抑制乙酰辅酶A羧化酶(ACC)、甾醇调节元件结合蛋白-1c(SREBP1)和哺乳动物雷帕霉素靶点(mTOR),并通过激活AMP活化激酶(AMPK)激活PPARα,从而减缓脂质积聚。此外,GMET通过激活AMPK和抑制活化蛋白激酶B(AKT)/IκB激酶(IKK)途径来抑制NF-κB途径,从而抑制肝细胞的炎症反应。通过与AMPK抑制剂dorsomorphin共同治疗,GMET对体内外脂质积聚和炎症的所有这些保护作用基本上被消除。总之,在脂肪性肝炎中,GMET减轻了脂质积聚和炎症,以保持正常的肝细胞功能。因此,GMET是一种新的潜在的多靶向化合物,可以改善脂肪性肝炎。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition

A growing proportion of the global adult and pediatric populations are currently affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from Lespedeza bicolor, could alleviate lipid accumulation and inflammatory responses in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid accumulation and attenuated inflammatory responses without cytotoxicity. Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), and activates PPARα by activating AMP-activated kinase (AMPK), leading to the alleviation of lipid accumulation. In addition, GMET suppresses the NF-κB pathway by activating AMPK and inhibiting the activated protein kinase B (AKT)/IκB-kinase (IKK) pathway, leading to the inhibition of the inflammatory response in hepatocytes. All these protective effects of GMET on lipid accumulation and inflammation in vivo and in vitro were largely abolished by co-treatment with dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid accumulation and inflammation to preserve normal hepatocyte function in steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to improve steatohepatitis.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
期刊最新文献
Saponins as potential novel NLRP3 inflammasome inhibitors for inflammatory disorders. Modulating versatile pathways using a cleavable PEG shell and EGFR-targeted nanoparticles to deliver CRISPR-Cas9 and docetaxel for triple-negative breast cancer inhibition. Ginsenoside Rg3 activates the immune function of CD8+ T cells via circFOXP1-miR-4477a-PD-L1 axis to induce ferroptosis in gallbladder cancer. Potential effects of a human milk oligosaccharide 6'-sialyllactose on angiotensin II-induced aortic aneurysm via p90RSK/TGF-β/SMAD2 signaling pathway. Akt-activated GSK3β inhibitory peptide effectively blocks tau hyperphosphorylation.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1