Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway
Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PP...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223001075 |
| _version_ | 1797894732851970048 |
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| author | Yiping Li Yang Liu Zhiwei Chen Kaiyue Tang Lili Yang Yuwei Jiang Jue Wang Ping Huang Jianyi Wang Peiyong Zheng Haiyan Song |
| author_facet | Yiping Li Yang Liu Zhiwei Chen Kaiyue Tang Lili Yang Yuwei Jiang Jue Wang Ping Huang Jianyi Wang Peiyong Zheng Haiyan Song |
| author_sort | Yiping Li |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD. |
| first_indexed | 2024-04-10T07:14:00Z |
| format | Article |
| id | doaj.art-585ee8d13c914e6a851996d4f5f54b15 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T07:14:00Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-585ee8d13c914e6a851996d4f5f54b152023-02-26T04:26:25ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-04-01160114319Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathwayYiping Li0Yang Liu1Zhiwei Chen2Kaiyue Tang3Lili Yang4Yuwei Jiang5Jue Wang6Ping Huang7Jianyi Wang8Peiyong Zheng9Haiyan Song10Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Collaborative Innovation Center for Biomedicine, Shanghai University of Medicine & Health Sciences, Shanghai 201318, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Teaching Experiment Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaInstitute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, ChinaDepartment of Liver Disease, Shanghai Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Corresponding authors.Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Corresponding authors.Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Corresponding authors.Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.http://www.sciencedirect.com/science/article/pii/S0753332223001075Non-alcoholic fatty liver diseaseProtopanaxadiolLipid metabolismAMPKSIRT1 |
| spellingShingle | Yiping Li Yang Liu Zhiwei Chen Kaiyue Tang Lili Yang Yuwei Jiang Jue Wang Ping Huang Jianyi Wang Peiyong Zheng Haiyan Song Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway Biomedicine & Pharmacotherapy Non-alcoholic fatty liver disease Protopanaxadiol Lipid metabolism AMPK SIRT1 |
| title | Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway |
| title_full | Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway |
| title_fullStr | Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway |
| title_full_unstemmed | Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway |
| title_short | Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway |
| title_sort | protopanaxadiol ameliorates nafld by regulating hepatocyte lipid metabolism through ampk sirt1 signaling pathway |
| topic | Non-alcoholic fatty liver disease Protopanaxadiol Lipid metabolism AMPK SIRT1 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223001075 |
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