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山莨菪碱通过与 MZF1 相互作用并针对乙型肝炎病毒基因的核心启动子发挥抗病毒作用。

Solamargine acts as an antiviral by interacting to MZF1 and targeting the core promoter of the hepatitis B virus gene.

机构信息

Department of Gastroenterology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003, China.

Master of Chinese medicine (studies and applications of internal Chinese medicines), Hong Kong Baptist University, Kowloon Tong, Hong Kong.

出版信息

Aging (Albany NY). 2024 Aug 10;16(15):11668-11682. doi: 10.18632/aging.206047.

Abstract

BACKGROUND

Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism.

METHOD

The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay.

RESULTS

By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.

摘要

背景

乙型肝炎病毒(HBV)感染仍然是全球健康的严重威胁,可导致多种肝脏疾病,包括急性和慢性肝炎、肝硬化、肝衰竭、肝细胞癌(HCC)等。目前国内外治疗乙型肝炎的药物主要有两类:干扰素(IFN)和核苷/核苷酸类似物(NAs)。近年来,天然化合物因其结构复杂、成分多样、高效低毒等特点,被认为是开发新型抗 HBV 药物的重要来源。许多研究表明,茄碱具有显著的抗癌活性,但抗病毒作用很少被研究。本研究旨在验证茄碱的抗 HBV 作用,并探讨其具体机制。

方法

采用反转录实时荧光定量 PCR(RT-qPCR)检测 HBV 前基因组 RNA(pgRNA)的相对表达。采用Northern blot 和 western blot 检测 HBV pgRNA 和靶蛋白的相对表达。采用 PCR 构建 HBV pg 启动子、ENII/BCP 及一系列基因缺失突变荧光报告载体。通过 Renilla 荧光素酶测定检测各突变体的荧光相对表达。

结果

茄碱通过与 MZF1(Myeloid zinc finger protein 1,MZF1)结合,抑制 HBV 核心启动子活性,降低前基因组 RNA 水平,从而抑制 HBV,发挥抗病毒作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5be9/11346786/6516b3e43b42/aging-16-206047-g001.jpg

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