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Protective effects of madecassoside, a triterpenoid from Centella asiatica, against oxidative stress in INS-1E cells
Swee Ching Tan1, Ramkumar Rajendran2,3, Subrat Kumar Bhattamisra3,4
1School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia.
Abstract:
Progressive decline in β cell function and reduction in the β cell mass is important in type 2 diabetes. Here, we tested the hypothesis that madecassoside's previously demonstrated in vivo protective effects on the β cell in experimental diabetes were exerted directly. We investigated the effects of madecassoside in protecting a β cell line (INS-1E) against a variety of agents. INS-1E cells were treated with madecassoside in the presence of high glucose (HG), a cytokine mixture, hydrogen peroxide (H2O2), or streptozotocin (STZ). HG, the cytokine mixture, H2O2 and STZ each produced a significant decrease in cell viability; this was significantly reversed by madecassoside. Pre-treatment with madecassoside reduced the number of apoptotic cells induced by HG, the cytokine mixture, H2O2, and STZ, and concentration-dependently reduced ROS production. Madecassoside also significantly enhanced glucose-induced insulin secretion. The results suggest that madecassoside's in vivo effects are exerted directly on the β cell.
Insights
Madecassoside directly protects pancreatic beta cells from damage in type 2 diabetes models. This compound enhances insulin secretion and reduces cell death, suggesting a direct therapeutic effect.
Area of Science:
- Endocrinology
- Cell Biology
- Pharmacology
Background:
- Progressive decline in pancreatic beta cell function and mass is a hallmark of type 2 diabetes.
- Previous studies indicated madecassoside possesses protective effects on beta cells in experimental diabetes models.
- The direct mechanisms underlying madecassoside's protective actions on beta cells remained unclear.
Purpose of the Study:
- To investigate whether madecassoside exerts its protective effects on pancreatic beta cells directly.
- To evaluate the impact of madecassoside on beta cell viability and apoptosis when exposed to various diabetogenic agents.
- To assess madecassoside's influence on reactive oxygen species (ROS) production and glucose-stimulated insulin secretion (GSIS).
Main Methods:
- Utilized the INS-1E rat insulinoma beta cell line.
- Treated cells with madecassoside in combination with high glucose (HG), a cytokine mixture, hydrogen peroxide (H2O2), or streptozotocin (STZ).
- Assessed cell viability, apoptosis, ROS production, and GSIS.
Main Results:
- Madecassoside significantly reversed the decrease in cell viability induced by HG, cytokines, H2O2, and STZ.
- Pre-treatment with madecassoside reduced apoptosis in beta cells exposed to these damaging agents.
- Madecassoside demonstrated a dose-dependent reduction in ROS production and enhanced glucose-induced insulin secretion.
Conclusions:
- Madecassoside directly protects pancreatic beta cells against various forms of chemical and metabolic stress.
- The compound mitigates beta cell apoptosis and oxidative stress.
- Madecassoside's direct actions on beta cells, including enhanced insulin secretion, support its potential therapeutic role in type 2 diabetes.
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