Protective effects of fermented Rosa roxburghii Tratt juice against ethanol‑induced hepatocyte injury by regulating the NRF2‑AMPK signaling pathway in AML‑12 cells

刺梨发酵汁通过调控 AML-12 细胞中的 NRF2-AMPK 信号通路对乙醇诱导的肝细胞损伤的保护作用

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作者:Lalai Zikela #, Zhuoli Yu #, Jindan Han #, Huilin Zhu, Dingli Wang, Xuezhu Wang, Songtao Li, Qiang Han

Abstract

Alcohol‑related liver disease (ALD) is a major health concern worldwide. In recent years, there has been growing interest in natural products and functional foods for preventing and treating ALD due to their potential antioxidant and hepatoprotective properties. Rosa roxburghii Tratt, known for its rich content of bioactive compounds, has demonstrated promising health benefits, including anti‑inflammatory and antioxidant effects. Fermentation has been utilized as a strategy to enhance the bioavailability and efficacy of natural products. In the present study, using a mixture of Rosa roxburghii Tratt juice, lotus leaf extract and grape seed proanthocyanidins fermented by Lactobacillus plantarum HH‑LP56, a novel fermented Rosa roxburghii Tratt (FRRT) juice was discovered that can prevent and regulate ethanol‑induced liver cell damage. Following fermentation, the pH was significantly decreased, and the content of VC and superoxide dismutase (SOD) were significantly increased, along with a noticeable enhancement in hydroxyl and 2,2‑diphenyl‑1‑picrylhydrazyl free radical scavenging abilities. Alpha Mouse liver 12 cells were exposed to ethanol for 24 h to establish an in vitro liver cell injury model. The present study evaluated the effects of FRRT on cell damage, lipid accumulation and oxidative stress markers. The results revealed that FRRT pretreatment (cells were pre‑treated with 2.5 and 5 mg/ml FRRT for 2 h) significantly reduced lipid accumulation and oxidative stress in liver cells. Mechanistically, FRRT regulated lipid metabolism by influencing key genes and proteins, such as AMP‑activated protein kinase, sterol regulatory element binding transcription factor 1 and Stearyl‑CoA desaturase‑1. Furthermore, FRRT enhanced antioxidant activity by increasing SOD activity, glutathione and catalase levels, while reducing reactive oxygen species and malondialdehyde levels. It also reversed the expression changes of ethanol‑induced oxidative stress‑related genes and proteins. In conclusion, a novel functional food ingredient may have been discovered with extensive potential applications. These findings indicated that FRRT has antioxidant properties and potential therapeutic benefits in addressing ethanol‑induced liver cell damage through its effects on liver lipid metabolism and oxidative stress.

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