清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Chaihu Guizhi Ganjiang Decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPARα mediated lipotoxicity

脂毒性 脂肪性肝炎 脂肪变性 医学 药理学 促炎细胞因子 纤维化 炎症 肝损伤 肝硬化 内科学 非酒精性脂肪肝 内分泌学 胰岛素抵抗 胰岛素 脂肪肝 疾病
作者
Hao Wu,Tianyu Lou,Mingxia Pan,Zuying Wei,Xiaoqin Yang,Lirong Liu,Menghan Feng,Lixia Shi,Biqiong Qu,Shiyu Cong,Kui Chen,Haolan Yang,Jie Liu,Yueting Li,Zhixin Jia,Hongbin Xiao
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:326: 117841-117841 被引量:3
标识
DOI:10.1016/j.jep.2024.117841
摘要

Nonalcoholic steatohepatitis (NASH) is a prominent cause of liver-related death that poses a threat to global health and is characterized by severe hepatic steatosis, lobular inflammation, and ballooning degeneration. To date, no Food and Drug Administration-approved medicine is commercially available. The Chaihu Guizhi Ganjiang Decoction (CGGD) shows potential curative effects on regulation of blood lipids and blood glucose, mitigation of organism inflammation, and amelioration of hepatic function. However, the overall regulatory mechanisms underlying its effects on NASH remain unclear. This study aimed to investigate the efficiency of CGGD on methionine- and choline-deficient (MCD)-induced NASH and unravel its underlying mechanisms. A NASH model of SD rats was established using an MCD diet for 8 weeks, and the efficacy of CGGD was evaluated based on hepatic lipid accumulation, inflammatory response, and fibrosis. The effects of CGGD on the intestinal barrier, metabolic profile, and differentially expressed genes (DEGs) profile were analyzed by integrating gut microbiota, metabolomics, and transcriptome sequencing to elucidate its mechanisms of action. In MCD-induced NASH rats, pathological staining demonstrated that CGGD alleviated lipid accumulation, inflammatory cell infiltration, and fibrosis in the hepatic tissue. After CGGD administration, liver index, liver weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) contents, liver triglycerides (TG), and free fatty acids (FFAs) were decreased, meanwhile, it down-regulated the level of proinflammatory mediators (TNF-α, IL-6, IL-1β, MCP-1), and up-regulated the level of anti-inflammatory factors (IL-4, IL-10), and the expression of liver fibrosis markers TGFβ, Acta2, Col1a1 and Col1a2 were weakened. Mechanistically, CGGD treatment altered the diversity of intestinal flora, as evidenced by the depletion of Allobaculum, Blautia, norank_f_Erysipelotrichaceae, and enrichment of the probiotic genera Roseburia, Lactobacillus, Lachnoclostridium, etc. The colonic histopathological results indicated that the gut barrier damage recovered in the CGGD treatment group, and the expression levels of colonic short-chain fatty acids (SCFAs)-specific receptors FFAR2, FFAR3, and tight junction (TJs) proteins ZO-1, Occludin, Claudin-1 were increased compared with those in the model group. Further metabolomic and transcriptomic analyses suggested that CGGD mitigated the lipotoxicity caused by glycerophospholipid and eicosanoid metabolism disorders by decreasing the levels of PLA2G4A, LPCAT1, COX2, and LOX5. In addition, CGGD could activate the inhibitory lipotoxic transcription factor PPARα, regulate the proteins of FABP1, APOC2, APOA2, and LPL to promote fatty acid catabolism, and suppress the TLR4/MyD88/NFκB pathway to attenuate NASH. Our study demonstrated that CGGD improved steatosis, inflammation, and fibrosis on NASH through enhancing intestinal barrier integrity and alleviating PPARα mediated lipotoxicity, which makes it an attractive candidate for potential new strategies for NASH prevention and treatment.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
21秒前
牛安荷完成签到,获得积分10
21秒前
Royal发布了新的文献求助10
27秒前
彩色的芷容完成签到 ,获得积分20
30秒前
GG完成签到 ,获得积分10
46秒前
46秒前
J陆lululu完成签到 ,获得积分10
1分钟前
Yolenders完成签到 ,获得积分10
1分钟前
naczx完成签到,获得积分10
1分钟前
1分钟前
1分钟前
仿真小学生完成签到,获得积分10
1分钟前
racill完成签到 ,获得积分10
1分钟前
土拨鼠完成签到 ,获得积分10
2分钟前
玩命的无春完成签到 ,获得积分10
2分钟前
brick2024完成签到,获得积分10
2分钟前
苏州九龙小7完成签到 ,获得积分10
2分钟前
3分钟前
Migue发布了新的文献求助10
3分钟前
ala完成签到,获得积分10
3分钟前
1461644768完成签到,获得积分10
3分钟前
菠萝包完成签到 ,获得积分10
3分钟前
bzdjsmw完成签到 ,获得积分10
4分钟前
菠萝炒蛋加饭完成签到 ,获得积分10
4分钟前
酷波er应助帮帮我好吗采纳,获得10
4分钟前
oaoalaa完成签到 ,获得积分10
5分钟前
Garrett完成签到 ,获得积分10
5分钟前
guoxingliu完成签到,获得积分10
5分钟前
大熊完成签到 ,获得积分10
5分钟前
bing完成签到 ,获得积分10
5分钟前
woxinyouyou完成签到,获得积分0
6分钟前
orixero应助帮帮我好吗采纳,获得10
6分钟前
SWIM666完成签到,获得积分10
6分钟前
果酱完成签到,获得积分10
6分钟前
6分钟前
huanghe完成签到,获得积分10
7分钟前
Owen应助帮帮我好吗采纳,获得10
7分钟前
数乱了梨花完成签到 ,获得积分10
7分钟前
南风完成签到 ,获得积分10
7分钟前
nano完成签到 ,获得积分10
7分钟前
高分求助中
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Defense against predation 800
Very-high-order BVD Schemes Using β-variable THINC Method 568
Chen Hansheng: China’s Last Romantic Revolutionary 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3137034
求助须知:如何正确求助?哪些是违规求助? 2788014
关于积分的说明 7784284
捐赠科研通 2444088
什么是DOI,文献DOI怎么找? 1299724
科研通“疑难数据库(出版商)”最低求助积分说明 625522
版权声明 600999