Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated the mechanisms of how green jackfruit flour (JF) ame...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-96944-1 |
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| author | Diwakar Suresh Bharathwaaj Gunaseelan Akshatha N. Srinivas Amith Bharadwaj James Joseph Megha Thomas Varughese Suchitha Satish Deepak Suvarna Prasanna K. Santhekadur Saravana Babu Chidambaram Ajay Duseja Divya P. Kumar |
| author_facet | Diwakar Suresh Bharathwaaj Gunaseelan Akshatha N. Srinivas Amith Bharadwaj James Joseph Megha Thomas Varughese Suchitha Satish Deepak Suvarna Prasanna K. Santhekadur Saravana Babu Chidambaram Ajay Duseja Divya P. Kumar |
| author_sort | Diwakar Suresh |
| collection | DOAJ |
| description | Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated the mechanisms of how green jackfruit flour (JF) ameliorates metabolic-dysfunction-associated steatohepatitis (MASH) and halts the progression to hepatocellular carcinoma (HCC). The study used murine models of MASH and MASH-HCC that closely mimic human MASLD. C57Bl/6 male mice were fed with chow or western diet with normal or sugar water for 12 weeks, then randomized to receive either 5 kcal% green jackfruit flour (JF) or an equal volume of placebo flour (PB). JF significantly reduced body weight, liver injury, and insulin resistance, and alleviated obesity, steatosis, inflammation, fibrosis, and tumor development in WDSW or WDSW/CCl4 mice compared to placebo. Furthermore, JF activated AMPK (AMP-activated protein kinase) and inhibited MAPK (mitogen-activated protein kinase) signaling pathways in MASH and MASH-HCC models, respectively. Sodium propionate treatment, the primary short-chain fatty acid entering the liver from JF’s soluble fiber microbial fermentation, further supported these mechanistic insights. Hence, our findings present strong evidence of JF’s therapeutic potential in attenuating MASH and MASH-HCC, warranting further investigation of JF’s efficacy as a dietary intervention in clinical trials. |
| format | Article |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-2fc1c95a397a4e3bb2e84847d02e44c02025-08-20T02:28:04ZengNature PortfolioScientific Reports2045-23222025-04-0115111910.1038/s41598-025-96944-1Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systemsDiwakar Suresh0Bharathwaaj Gunaseelan1Akshatha N. Srinivas2Amith Bharadwaj3James Joseph4Megha5Thomas Varughese6Suchitha Satish7Deepak Suvarna8Prasanna K. Santhekadur9Saravana Babu Chidambaram10Ajay Duseja11Divya P. Kumar12Department of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and ResearchDepartment of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and ResearchDepartment of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and ResearchDepartment of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and ResearchGod’s Own Food Solutions Pvt LtdCentre For Ayurveda Biology and Holistic Nutrition, University of Transdisciplinary Health Sciences and TechnologyDepartment of Surgical Oncology, St. Joseph’s Hospital TrustDepartment of Pathology, JSS Medical College and Hospital, JSS Academy of Higher Education and ResearchDepartment of Gastroenterology, JSS Medical College and Hospital, JSS Academy of Higher Education and ResearchDepartment of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and ResearchDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Hepatology, Postgraduate Institute of Medical Education & ResearchDepartment of Biochemistry, CEMR Laboratory, JSS Medical College, JSS Academy of Higher Education and ResearchAbstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated the mechanisms of how green jackfruit flour (JF) ameliorates metabolic-dysfunction-associated steatohepatitis (MASH) and halts the progression to hepatocellular carcinoma (HCC). The study used murine models of MASH and MASH-HCC that closely mimic human MASLD. C57Bl/6 male mice were fed with chow or western diet with normal or sugar water for 12 weeks, then randomized to receive either 5 kcal% green jackfruit flour (JF) or an equal volume of placebo flour (PB). JF significantly reduced body weight, liver injury, and insulin resistance, and alleviated obesity, steatosis, inflammation, fibrosis, and tumor development in WDSW or WDSW/CCl4 mice compared to placebo. Furthermore, JF activated AMPK (AMP-activated protein kinase) and inhibited MAPK (mitogen-activated protein kinase) signaling pathways in MASH and MASH-HCC models, respectively. Sodium propionate treatment, the primary short-chain fatty acid entering the liver from JF’s soluble fiber microbial fermentation, further supported these mechanistic insights. Hence, our findings present strong evidence of JF’s therapeutic potential in attenuating MASH and MASH-HCC, warranting further investigation of JF’s efficacy as a dietary intervention in clinical trials.https://doi.org/10.1038/s41598-025-96944-1NAFLDNASHMASLDLiver injuryInflammationMetabolic syndrome |
| spellingShingle | Diwakar Suresh Bharathwaaj Gunaseelan Akshatha N. Srinivas Amith Bharadwaj James Joseph Megha Thomas Varughese Suchitha Satish Deepak Suvarna Prasanna K. Santhekadur Saravana Babu Chidambaram Ajay Duseja Divya P. Kumar Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems Scientific Reports NAFLD NASH MASLD Liver injury Inflammation Metabolic syndrome |
| title | Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems |
| title_full | Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems |
| title_fullStr | Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems |
| title_full_unstemmed | Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems |
| title_short | Green jackfruit flour ameliorates MASH and development of HCC via the AMPK and MAPK signaling pathways in experimental model systems |
| title_sort | green jackfruit flour ameliorates mash and development of hcc via the ampk and mapk signaling pathways in experimental model systems |
| topic | NAFLD NASH MASLD Liver injury Inflammation Metabolic syndrome |
| url | https://doi.org/10.1038/s41598-025-96944-1 |
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