Amr Negm, Amira A El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer M Shawky, Ezat A Mersal
{"title":"绿原酸通过调节PI3K/AKT/mTOR自噬途径改善ccl4诱导的肝纤维化","authors":"Amr Negm, Amira A El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer M Shawky, Ezat A Mersal","doi":"10.2174/0118715206357043250116063202","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.</p><p><strong>Objective: </strong>Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.</p><p><strong>Methods: </strong>Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.</p><p><strong>Results: </strong>CCl4 elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.</p><p><strong>Conclusion: </strong>Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl4 by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chlorogenic Acid Ameliorates CCl4-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.\",\"authors\":\"Amr Negm, Amira A El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer M Shawky, Ezat A Mersal\",\"doi\":\"10.2174/0118715206357043250116063202\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.</p><p><strong>Objective: </strong>Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.</p><p><strong>Methods: </strong>Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.</p><p><strong>Results: </strong>CCl4 elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.</p><p><strong>Conclusion: </strong>Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl4 by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.</p>\",\"PeriodicalId\":7934,\"journal\":{\"name\":\"Anti-cancer agents in medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-01-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-cancer agents in medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0118715206357043250116063202\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-cancer agents in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0118715206357043250116063202","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Chlorogenic Acid Ameliorates CCl4-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.
Background: Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.
Objective: Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.
Methods: Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.
Results: CCl4 elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.
Conclusion: Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl4 by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.
期刊介绍:
Formerly: Current Medicinal Chemistry - Anti-Cancer Agents.
Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents.
Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication.
Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.