Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability
<b>Background/Objectives</b>: Gypenosides (Gps) are the main active compounds of <i>Gynostemma</i> and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify th...
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2025-07-01
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| author | Rong Wang Xue-Feng Liu Kuan Yang Li-Li Yu Shao-Jing Liu Na-Na Wang Yun-Mei Chen Ya-Qi Hu Bei Qin |
| author_facet | Rong Wang Xue-Feng Liu Kuan Yang Li-Li Yu Shao-Jing Liu Na-Na Wang Yun-Mei Chen Ya-Qi Hu Bei Qin |
| author_sort | Rong Wang |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Gypenosides (Gps) are the main active compounds of <i>Gynostemma</i> and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify the molecular mechanisms of Gps in ameliorating glucose dysregulation. <b>Methods</b>: Qualitative and quantitative analyses on the chemical components of Gps were performed, respectively. Type 2 diabetes mellitus mouse models were established, and the mice were subsequently treated with Gps at doses of 200, 100, or 50 mg/kg for 4 weeks. Biochemical markers were measured. Histopathological assessments of hepatic and colonic tissues were conducted. The compositions of the intestinal microbiota, short-chain fatty acids (SCFAs), and bile acids (BAs) in fecal samples were analyzed. Western blotting was applied to examine the activation of relevant signaling pathways. <b>Results</b>: Gps have potent regulatory effects on metabolic homeostasis by improving glucose and lipid profiles and alleviating hepatic tissue damage. Treatment with Gps significantly reduced serum levels of lipopolysaccharides and key pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, Gps enhanced the integrity of the gut barrier by upregulating the level of tight junction proteins (ZO-1 and occludin). Microbiota profiling revealed that Gps markedly increased microbial diversity and richness, decreased the ratio of <i>Firmicutes</i>/<i>Bacteroidetes</i>, and elevated <i>Bacteroidia</i> abundance from the phylum to the genus level. Targeted metabolomics further demonstrated that Gps modulated gut microbial metabolites by promoting SCFA production and reshaping BA profiles. Specifically, Gps elevated the primary-to-secondary BA ratio while reducing the 12α-hydroxylated to non-12α-hydroxylated BA ratio. Mechanistically, Western blotting demonstrated that Gps triggered the hepatic PI3K/AKT pathway and the intestinal BA/FXR/FGF15 axis, suggesting the coordinated regulation of metabolic and gut–liver axis signaling pathways. <b>Conclusions</b>: Gps significantly ameliorate hyperglycemia and hyperlipidemia through a multifaceted mechanism involving gut microbiota modulation, the restoration of intestinal barrier function, and the regulation of microbial metabolites such as SCFAs and BAs. These findings offer novel insights into their mechanism of action via the gut–liver axis. |
| format | Article |
| id | doaj-art-2abf9caf03784c33ae3ef1f1042e5111 |
| institution | DOAJ |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj-art-2abf9caf03784c33ae3ef1f1042e51112025-08-20T03:08:05ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-07-0147751510.3390/cimb47070515Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal PermeabilityRong Wang0Xue-Feng Liu1Kuan Yang2Li-Li Yu3Shao-Jing Liu4Na-Na Wang5Yun-Mei Chen6Ya-Qi Hu7Bei Qin8Xi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Institute of Food and Drug Control, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi’an Medical University, Xi’an 710021, China<b>Background/Objectives</b>: Gypenosides (Gps) are the main active compounds of <i>Gynostemma</i> and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify the molecular mechanisms of Gps in ameliorating glucose dysregulation. <b>Methods</b>: Qualitative and quantitative analyses on the chemical components of Gps were performed, respectively. Type 2 diabetes mellitus mouse models were established, and the mice were subsequently treated with Gps at doses of 200, 100, or 50 mg/kg for 4 weeks. Biochemical markers were measured. Histopathological assessments of hepatic and colonic tissues were conducted. The compositions of the intestinal microbiota, short-chain fatty acids (SCFAs), and bile acids (BAs) in fecal samples were analyzed. Western blotting was applied to examine the activation of relevant signaling pathways. <b>Results</b>: Gps have potent regulatory effects on metabolic homeostasis by improving glucose and lipid profiles and alleviating hepatic tissue damage. Treatment with Gps significantly reduced serum levels of lipopolysaccharides and key pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, Gps enhanced the integrity of the gut barrier by upregulating the level of tight junction proteins (ZO-1 and occludin). Microbiota profiling revealed that Gps markedly increased microbial diversity and richness, decreased the ratio of <i>Firmicutes</i>/<i>Bacteroidetes</i>, and elevated <i>Bacteroidia</i> abundance from the phylum to the genus level. Targeted metabolomics further demonstrated that Gps modulated gut microbial metabolites by promoting SCFA production and reshaping BA profiles. Specifically, Gps elevated the primary-to-secondary BA ratio while reducing the 12α-hydroxylated to non-12α-hydroxylated BA ratio. Mechanistically, Western blotting demonstrated that Gps triggered the hepatic PI3K/AKT pathway and the intestinal BA/FXR/FGF15 axis, suggesting the coordinated regulation of metabolic and gut–liver axis signaling pathways. <b>Conclusions</b>: Gps significantly ameliorate hyperglycemia and hyperlipidemia through a multifaceted mechanism involving gut microbiota modulation, the restoration of intestinal barrier function, and the regulation of microbial metabolites such as SCFAs and BAs. These findings offer novel insights into their mechanism of action via the gut–liver axis.https://www.mdpi.com/1467-3045/47/7/515gypenosidestype 2 diabetes mellitusgut microbiotashort-chain fatty acidsbile acids |
| spellingShingle | Rong Wang Xue-Feng Liu Kuan Yang Li-Li Yu Shao-Jing Liu Na-Na Wang Yun-Mei Chen Ya-Qi Hu Bei Qin Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability Current Issues in Molecular Biology gypenosides type 2 diabetes mellitus gut microbiota short-chain fatty acids bile acids |
| title | Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability |
| title_full | Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability |
| title_fullStr | Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability |
| title_full_unstemmed | Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability |
| title_short | Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability |
| title_sort | gypenosides alleviate hyperglycemia by regulating gut microbiota metabolites and intestinal permeability |
| topic | gypenosides type 2 diabetes mellitus gut microbiota short-chain fatty acids bile acids |
| url | https://www.mdpi.com/1467-3045/47/7/515 |
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