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多糖通过调节miR-140-5p相关的抗氧化机制减轻对乙酰氨基酚诱导的肝损伤。

polysaccharide attenuates acetaminophen-induced liver injury by regulating the miR-140-5p-related antioxidant mechanism.

作者信息

Cai Liangliang, Xu Lixing, Shen Kai, Wang Qin, Ni Ronghua, Xu Xin, Ma Xiaofei

机构信息

Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, 226001, PR China.

School of Pharmacy, Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets, Nantong University, Nantong, 226001, PR China.

出版信息

J Tradit Complement Med. 2024 Jan 16;14(4):467-476. doi: 10.1016/j.jtcme.2024.01.006. eCollection 2024 Jul.

Abstract

STRP1, a polysaccharide active ingredient isolated from the traditional Chinese medicine , has demonstrated a protective effect against acetaminophen (APAP)-induced liver injury (AILI). The underlying molecular mechanism was investigated in this study. Here, an acute liver damage mouse model was generated by APAP (400 mg/kg) and used to identify the protective effect of STRP1 (200 mg/kg) on mouse livers. In vitro cell experiments were used to further verify the related signaling pathways. Initially, in our study, STRP1 treatment reduced APAP-induced liver injury by decreasing aminotransferase activity and cell apoptosis and increasing cell proliferation. Furthermore, STRP1 treatment significantly increased expression and alleviated oxidative stress caused by reactive oxygen species in AILI. Based on bioinformatics and experimental studies, miR-140-5p was identified and found to be reduced by STRP1, increasing expression. Additionally, played an important role in the protective impact of STRP1-suppressed miR-140-5p expression. Generally, these results showed that STRP1-mediated suppression of miR-140-5p expression mitigates AILI by activating the -mediated Nrf2-Keap1 pathway. This study revealed that STRP1 might be a potential treatment agent for AILI.

摘要

STRP1是一种从传统中药中分离出的多糖活性成分,已证明其对乙酰氨基酚(APAP)诱导的肝损伤(AILI)具有保护作用。本研究对其潜在的分子机制进行了探究。在此,通过APAP(400mg/kg)建立急性肝损伤小鼠模型,用于确定STRP1(200mg/kg)对小鼠肝脏的保护作用。体外细胞实验用于进一步验证相关信号通路。最初,在我们的研究中,STRP1治疗通过降低转氨酶活性和细胞凋亡并增加细胞增殖,减轻了APAP诱导的肝损伤。此外,STRP1治疗显著增加了[此处原文缺失具体内容]的表达,并减轻了AILI中活性氧引起的氧化应激。基于生物信息学和实验研究,鉴定出miR-140-5p,发现其表达被STRP1降低,而[此处原文缺失具体内容]的表达增加。此外,[此处原文缺失具体内容]在STRP1抑制miR-140-5p表达的保护作用中发挥了重要作用。总体而言,这些结果表明,STRP1介导的miR-140-5p表达抑制通过激活[此处原文缺失具体内容]介导的Nrf2-Keap1途径减轻了AILI。本研究表明,STRP1可能是一种治疗AILI的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5f3/11259709/e57cfd13b0d2/ga1.jpg

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