Madecassoside Shield Against Cell Damage From Oxidative Stress

Jim Crocker
11th February, 2024

Madecassoside Shield Against Cell Damage From Oxidative Stress

Indian pennywort (Centella asiatica), source of madecassoside.

Photo adapted from: Tony Rebelo / CC BY SA (Source)
Type 2 diabetes is a growing global health concern, largely due to the progressive loss of function and number of beta cells within the pancreas. Beta cells are responsible for producing insulin, the hormone that regulates blood sugar levels. When these cells are damaged or die, the body struggles to maintain healthy glucose levels, leading to the development of the disease. Researchers at the International Medical University (IMU) have been investigating potential protective agents for these vital cells, and their recent work[1] focuses on a compound called madecassoside. The study aimed to determine if madecassoside, which had previously shown promise in animal models of diabetes, could directly protect beta cells. Previous research has highlighted the complexity of oxidative stress in beta cell damage[2]. Oxidative stress occurs when there’s an imbalance between the production of reactive oxygen species (ROS) – unstable molecules that can damage cells – and the body’s ability to neutralize them. Different methods of inducing oxidative stress can yield varying results, suggesting that the type of stress matters when evaluating potential treatments. This new study sought to test madecassoside against multiple forms of stress that beta cells experience in a diabetic environment. The IMU researchers tested madecassoside on a line of beta cells grown in the lab (INS-1E cells). They exposed these cells to four different damaging agents: high glucose (HG), a mixture of cytokines (signaling molecules that promote inflammation), hydrogen peroxide (H2O2), and streptozotocin (STZ). Each of these agents independently caused a significant decrease in cell viability – essentially, the cells began to die. However, when madecassoside was present, it significantly reversed this effect, protecting the cells from damage. Further investigation revealed that madecassoside reduced the number of cells undergoing apoptosis, or programmed cell death, induced by all four damaging agents. Apoptosis is a natural process, but in diabetes, it occurs at an accelerated rate in beta cells. Importantly, madecassoside also reduced the production of ROS in a concentration-dependent manner, meaning the more madecassoside present, the lower the ROS levels. This aligns with earlier findings demonstrating madecassoside’s ability to combat oxidative stress in other cell types[3], where it was shown to protect endothelial cells from H2O2-induced injury by reducing ROS and preventing cell death. The study also examined insulin secretion. Beta cells’ primary function is to release insulin in response to glucose. The researchers found that madecassoside actually enhanced glucose-induced insulin secretion, suggesting it not only protects cells from damage but also improves their function. These findings suggest that the protective effects of madecassoside observed in previous animal studies are likely due to a direct action on the beta cells themselves. The study builds on the understanding that high glucose levels can be toxic to beta cells, a phenomenon known as glucotoxicity[4]. This toxicity involves multiple mechanisms, including oxidative stress, and madecassoside appears to counteract at least one of these mechanisms – oxidative stress – thereby preserving beta cell function. The ability of madecassoside to protect against multiple stressors – high glucose, inflammation, and direct toxins like H2O2 and STZ – is particularly noteworthy, as beta cells in type 2 diabetes are exposed to a complex combination of these challenges.

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References

Main Study

1) Protective effects of madecassoside, a triterpenoid from Centella asiatica, against oxidative stress in INS-1E cells.

Published 10th February, 2024

https://doi.org/10.1080/14786419.2024.2315499

Related Studies

2) Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells.

https://doi.org/10.1155/2015/859048

3) Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress.

https://doi.org/10.1002/jbt.21434

4) The molecular mechanisms of pancreatic β-cell glucotoxicity: recent findings and future research directions.

https://doi.org/10.1016/j.mce.2012.08.003


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