Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway

Area of Science:

• Cardiovascular Research
• Pharmacology
• Cell Biology

Background:

• Doxorubicin (DOX) chemotherapy increases endothelial permeability, leading to direct cardiomyocyte damage.
• Reactive oxygen species (ROS) are key mediators of DOX-induced cardiotoxicity.
• Mangiferin (MGN), a natural antioxidant, may offer protective effects against drug-induced cellular damage.

Purpose of the Study:

• To investigate the protective effects of Mangiferin (MGN) against Doxorubicin (DOX)-induced cytotoxicity in human umbilical vein endothelial cells (HUVECs).
• To elucidate the underlying molecular mechanisms, focusing on the Nrf2 signaling pathway.

Main Methods:

• HUVECs were treated with DOX and varying concentrations of MGN.
• Assays included caspase-3 activity, TUNEL staining for DNA fragmentation, and Western blot analysis for protein expression.
• Nrf2 expression and the PI3K/AKT pathway activation were specifically examined.

Main Results:

• DOX significantly increased ROS generation, apoptosis markers (caspase-3, TUNEL-positive cells), and PARP cleavage, while decreasing Bcl-2 expression.
• MGN treatment (20 μM) effectively antagonized these DOX-induced effects.
• MGN upregulated Nrf2 expression and its downstream targets, mediated by the PI3K/AKT pathway.

Conclusions:

• Mangiferin (MGN) protects HUVECs from Doxorubicin (DOX)-induced apoptosis and cytotoxicity.
• The protective mechanism involves the activation of the PI3K/AKT/Nrf2/HO-1 signaling pathway.
• MGN holds potential for mitigating severe Doxorubicin toxicity in vascular endothelial cells.