Morin hydrate rebalances the miR-34a/Sirt1/HMGB1 pathway and abrogates radiation-induced nephritis via targeting Nrf2-miR-125b axis

Abstract

Morin hydrate (MH), a natural substance that lessens cell death, has been shown to have renal protective effects; however, the prospective molecular mechanism behind this response still unclear. The current study aimed to throw more light on the principal mechanism of morin hydrate (MH) in alleviating the acute kidney injury by ionizing radiation (IR) in vivo. Animals were divided into 4groups (Groups: control, (5Gy) irradiated (IRR), (40 mg/kg) MH, and MH + IRR). The results indicated that MH could significantly inhibit kidney damage and restore its structure and function (reduced urea by 55.86 % and creatinine by 55.24 %). In mechanism, MH prevented IR-induced kidney fibrosis and blocked the miR34a and HMGB1/TIMP-2 signaling cascades to effectively inhibit the renal inflammatory response; and prevented IR-induced oxidative stress (OS) by activating the Sirt1/Nrf2/miR-125b signaling axis and stimulating the synthesis of several antioxidant enzymes. MH reduced lipid peroxidation (36.96 %) by reducing the reactive oxygen species (61.9 %) production and rising antioxidant enzymes levels thus hindering inflammatory response and alleviating IR-induced kidney fibrosis. In conclusion, we proposed that MH can prevent radiation-induced nephritis and fibrosis by rebalancing the miR-34a/Sirt1/HMGB1 pathway and targeting Nrf2-miR-125b axis.