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丁酸产生膳食补充剂通过调节 Nrf2 介导的肝氧化应激和肠道微生物群预防急性酒精性肝损伤。

A Butyrate-Yielding Dietary Supplement Prevents Acute Alcoholic Liver Injury by Modulating Nrf2-Mediated Hepatic Oxidative Stress and Gut Microbiota.

机构信息

Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

Department of Microbiology, Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia.

出版信息

Int J Mol Sci. 2024 Aug 30;25(17):9420. doi: 10.3390/ijms25179420.

Abstract

Alcoholic liver disease (ALD) is a globally prevalent form of liver disease for which there is no effective treatment. Recent studies have found that a significant decrease in butyrate was closely associated with ALD development. Given the low compliance and delivery efficiency associated with oral-route butyrate administration, a highly effective butyrate-yielding dietary supplement, butyrylated high-amylose maize starch (HAMSB), is a good alternative approach. Here, we synthesized HAMSB, evaluated the effect of HAMSB on acute ALD in mice, compared its effect with that of oral administration of butyrate, and further studied the potential mechanism of action. The results showed HAMSB alleviated acute ALD in mice, as evidenced by the inhibition of hepatic-function impairment and the improvement in liver steatosis and lipid metabolism; in these respects, HAMSB supplementation was superior to oral sodium butyrate administration. These improvements can be attributed to the reduction of oxidative stress though the regulation of Nrf2-mediated antioxidant signaling in the liver and the improvement in the composition and function of microbiota in the intestine. In conclusion, HAMSB is a safe and effective dietary supplement for preventing acute ALD that could be useful as a disease-modifying functional food or candidate medicine.

摘要

酒精性肝病 (ALD) 是一种全球普遍存在的肝脏疾病,目前尚无有效的治疗方法。最近的研究发现,丁酸盐的显著减少与 ALD 的发展密切相关。鉴于口服丁酸盐给药的低顺应性和递送效率,高效产丁酸膳食补充剂丁酰化高直链玉米淀粉 (HAMSB) 是一种很好的替代方法。在这里,我们合成了 HAMSB,评估了 HAMSB 对小鼠急性 ALD 的影响,将其与口服丁酸盐的效果进行了比较,并进一步研究了其潜在的作用机制。结果表明, HAMSB 缓解了小鼠的急性 ALD,表现为肝功能损伤的抑制和肝脂肪变性及脂质代谢的改善;在这些方面, HAMSB 补充优于口服丁酸钠给药。这些改善可归因于通过调节肝脏中 Nrf2 介导的抗氧化信号来减少氧化应激,以及改善肠道中微生物群落的组成和功能。总之, HAMSB 是一种安全有效的预防急性 ALD 的膳食补充剂,可作为一种疾病修饰功能性食品或候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f733/11395132/5e3b9fa83d05/ijms-25-09420-g001.jpg

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