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Morinda officinalis oligosaccharides attenuate mitochondria-associated ferroptosis via the NOX4/mitoGPX4 pathway in myocardial ischemia‒reperfusion injury

Year: 2025

Type: article

Abstract: Aim: oligosaccharides (MOO) on ischemia-reperfusion (I/R) injury and the possible mechanisms involved. Methods: Myocardial I/R injury were induced by left anterior descending branch ligation. MOO pretreatment was given orally 2 weeks prior to ischemic treatment. Echocardiograms, biochemical parameters, and histological and immunohistochemical analyses were used to determine the benefits of MOO on myocardial I/R injury. Oxidative stress and ferroptosis were examined by biochemical parameters, Western blot, immunohistochemistry, and Tunel staining. Results: MOO improved cardiac function and reduced myocardial oxidative stress and ferroptosis, which was associated with the inhibition of NADPH Oxidase 4 (NOX4) expression. Whereas, the upregulation of NOX4 abolished the benefits of MOO. Furthermore, MOO enhanced mitochondrial superoxide dismutase 2 (SOD2) activity and stimulated the mitochondrial translocation of glutathione peroxidase 4 (mitoGPX4) by inhibiting NOX4. Mitochondria-specific GPX4 overexpression attenuated mitochondrial oxidative stress and suppressed mitochondria-associated ferroptosis in cardiomyocytes that suffered from hypoxia-reoxygenation (H/R) injury, even after NOX4 overexpression. Conclusion: These results indicate the beneficial effects of MOO on myocardial I/R injury by suppressing oxidative stress and mitochondria-associated ferroptosis through NOX4/mitoGPX4 pathway.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2025.1605513