Mangiferin alleviates endoplasmic reticulum stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis

Abstract

<jats:title>Abstract</jats:title> <jats:p>This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3′-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.</jats:p>

Perspectives on the potential of Mangiferin as a nutraceutical: a review

“…The drug's sequential dosing compromises heart activity, eventually leading to cardiac failure and death. Ultrastructural alterations in DOX-treated cardiac tissues, such as the development of vacuoles, sarcomere disruption and myocyte necrosis, corroborate this theory (Prabhu et al, 2006;Li et al, 2020aLi et al, , 2020b.…”

“…Mangiferin also serves as a memory enhancer and aids in the learning process. Mangiferin's ability to reduce neuroinflammation and brain oxidative damage caused by stress is equally impressive (Li et al, 2020a(Li et al, , 2020b.…”

EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis

“…In this study, we found that EETs reduced intracellular ROS content and ERS levels in senescent AECs. A large number of studies have shown that the key intracellular anti-oxidant factor Nrf2 and its downstream target gene HO-1 have a significant inhibitory effect on ERS [ 27 , 28 ]. In combination with this study, EETs could promote the protein expression of Nrf2 and HO-1 in AECs.…”

“…Upon oxidative stress, Nrf2 is released from Keap1 and transferred to the nucleus to activate downstream gene expression, including heme oxygenase-1 (HO-1), thus playing an anti-oxidant effect [ 26 ]. Studies have shown that increased expression of Nrf2 inhibits ERS [ 27 , 28 ]. Abnormal Nrf2 signaling has been found in a variety of age-related diseases, including pulmonary fibrosis [ 29 ].…”

Mangiferin for the Management of Liver Diseases: A Review

“…The CCl 4 challenge was downregulated with antioxidant enzymes, including glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD), along with elevated inflammation cytokines, including TNF-α, IL-1β and IL-6 in mice [ 79 ]. Interestingly, several studies have demonstrated the effects of mangiferin on oxidative stress and inflammation [ 80 ]. It has been reported that mangiferin alleviated acute liver injury by promoting the antioxidant HO-1 and reducing the production of TNF-α [ 81 , 82 ].…”