Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells
Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate th...
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MDPI AG
2025-05-01
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| author | Hui-Hsuan Lin Pei-Rong Yu Chiao-Yun Tseng Ming-Shih Lee Jing-Hsien Chen |
| author_facet | Hui-Hsuan Lin Pei-Rong Yu Chiao-Yun Tseng Ming-Shih Lee Jing-Hsien Chen |
| author_sort | Hui-Hsuan Lin |
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| description | Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment–insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS. |
| format | Article |
| id | doaj-art-2a667a43ecc34e099594fd36309313ea |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-2a667a43ecc34e099594fd36309313ea2025-08-20T02:33:39ZengMDPI AGAntioxidants2076-39212025-05-0114559510.3390/antiox14050595Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 CellsHui-Hsuan Lin0Pei-Rong Yu1Chiao-Yun Tseng2Ming-Shih Lee3Jing-Hsien Chen4Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung City 40201, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung City 40201, TaiwanDepartment of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, TaiwanClinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, TaiwanMetabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment–insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS.https://www.mdpi.com/2076-3921/14/5/595metabolic syndromelotus seedpod extractlipid dysmetabolisminsulin resistance |
| spellingShingle | Hui-Hsuan Lin Pei-Rong Yu Chiao-Yun Tseng Ming-Shih Lee Jing-Hsien Chen Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells Antioxidants metabolic syndrome lotus seedpod extract lipid dysmetabolism insulin resistance |
| title | Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells |
| title_full | Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells |
| title_fullStr | Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells |
| title_full_unstemmed | Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells |
| title_short | Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells |
| title_sort | protective effects of lotus seedpod extract on hepatic lipid and glucose metabolism via ampk associated mechanisms in a mouse model of metabolic syndrome and oleic acid induced hepg2 cells |
| topic | metabolic syndrome lotus seedpod extract lipid dysmetabolism insulin resistance |
| url | https://www.mdpi.com/2076-3921/14/5/595 |
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