Integrated metabolomics and proteomics revealed mangiferin alleviating oxidative stress and mitochondrial dysfunction of HT22 cells via regulating the abnormal metabolic pathways

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease, and prevalent health concern in modern society. Currently, there is a lack of effective therapeutic drugs. Mangiferin (MGF), an extract of mango, has the potential to improve neurodegenerative diseases, but the mechanism of MGF in the treatment of AD has not been deeply investigated. In this study, L-glutamic acid was used to induce oxidative damage in HT22 cells, and we studied the protective effect of MGF on injured neuronal cells. After MGF treatment, the HT22 cell morphology tended to be normal, apoptosis decreased, and ROS levels decreased. Proteomics enrichment analysis showed that autophagy animal and citrate cycle (TCA cycle) were the most significantly changed pathways for MGF anti-AD enrichment, and cysteine and methionine metabolism also played an important role. A total of 27 metabolite biomarkers associated with AD risk were identified by metabolomics analysis, 12 of which were significantly regulated by MGF. Through the combined analysis of proteomics and metabolomics, it was found that MGF could significantly regulate cysteine and methionine metabolism and the citrate cycle (TCA cycle) metabolic pathway and reduce the oxidative damage induced by glutamate, and thereby oxidative stress can be alleviated, and MGF can also regulate ATP content, mitochondrial function, and alleviate cognitive dysfunction of AD.