Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments
IntroductionAcute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and choleste...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1485915/full |
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| author | Xuanlin Zhao Fan Li Ao Wen Xiuxian Yu Xinrui Xu Chengyu Wan Yu Cao Guang Xin Wen Huang |
| author_facet | Xuanlin Zhao Fan Li Ao Wen Xiuxian Yu Xinrui Xu Chengyu Wan Yu Cao Guang Xin Wen Huang |
| author_sort | Xuanlin Zhao |
| collection | DOAJ |
| description | IntroductionAcute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated.MethodsThe present study employed network pharmacology combined with experimental verification to explore the protective effect of stigmasterol on AP and its molecular mechanism in a sodium taurocholate (STC)-induced AP mouse model.ResultsProtein-protein interaction (PPI) analysis pinpointed out MAPK3, also named as ERK1, as a promising stigmasterol target in AP therapy. Molecular docking analysis further revealed a strong binding capacity of stigmasterol to ERK1 (−6.57 kL/mol). Furthermore, both in vivo and in vitro studies demonstrated that stigmasterol treatment notably attenuated STC-induced pancreatic injury, as evidented by decreased serum levels of lipase and amylase, improved systemic inflammation, and reduced acinar cell necrosis. At the molecular level, stigmasterol treatment exhibited a significant inhibition on STC-induced activation of ERK signaling pathway in pancreatic acinar cells, leading to the transition of acinar cell death from necrosis to apoptosis, thereby preventing acinar cell necrosis-induced systemic inflammation.ConclusionThis study demonstrated that stigmasterol exhibits a significant protective effect aganist AP, at least in part through enhancing acinar cell apoptosis via modulating the ERK signaling pathways. |
| format | Article |
| id | doaj-art-9d9120427acf40a9b7aa53edc7bac75e |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-9d9120427acf40a9b7aa53edc7bac75e2025-08-20T02:40:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-12-011510.3389/fphar.2024.14859151485915Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experimentsXuanlin Zhao0Fan Li1Ao Wen2Xiuxian Yu3Xinrui Xu4Chengyu Wan5Yu Cao6Guang Xin7Wen Huang8West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Emergency Medicine, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaWest China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaIntroductionAcute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated.MethodsThe present study employed network pharmacology combined with experimental verification to explore the protective effect of stigmasterol on AP and its molecular mechanism in a sodium taurocholate (STC)-induced AP mouse model.ResultsProtein-protein interaction (PPI) analysis pinpointed out MAPK3, also named as ERK1, as a promising stigmasterol target in AP therapy. Molecular docking analysis further revealed a strong binding capacity of stigmasterol to ERK1 (−6.57 kL/mol). Furthermore, both in vivo and in vitro studies demonstrated that stigmasterol treatment notably attenuated STC-induced pancreatic injury, as evidented by decreased serum levels of lipase and amylase, improved systemic inflammation, and reduced acinar cell necrosis. At the molecular level, stigmasterol treatment exhibited a significant inhibition on STC-induced activation of ERK signaling pathway in pancreatic acinar cells, leading to the transition of acinar cell death from necrosis to apoptosis, thereby preventing acinar cell necrosis-induced systemic inflammation.ConclusionThis study demonstrated that stigmasterol exhibits a significant protective effect aganist AP, at least in part through enhancing acinar cell apoptosis via modulating the ERK signaling pathways.https://www.frontiersin.org/articles/10.3389/fphar.2024.1485915/fullstigmasterolacute pancreatitisapoptosisnetwork pharmacologymolecular docking |
| spellingShingle | Xuanlin Zhao Fan Li Ao Wen Xiuxian Yu Xinrui Xu Chengyu Wan Yu Cao Guang Xin Wen Huang Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments Frontiers in Pharmacology stigmasterol acute pancreatitis apoptosis network pharmacology molecular docking |
| title | Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments |
| title_full | Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments |
| title_fullStr | Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments |
| title_full_unstemmed | Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments |
| title_short | Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/in vivo experiments |
| title_sort | elucidating the mechanism of stigmasterol in acute pancreatitis treatment insights from network pharmacology and in vitro in vivo experiments |
| topic | stigmasterol acute pancreatitis apoptosis network pharmacology molecular docking |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1485915/full |
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