Glabridin inhibits proliferation and migration in hepatocellular carcinoma by regulating multi-targets.

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2024-11-06 DOI:10.1016/j.jep.2024.119022

Fei Wang, Chong Yuan, Yi Lu, Mojiao Wu, Hezhen Wu, Yifei Liu, Yanfang Yang

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引用次数: 0

Abstract

Ethnopharmacological relevance: Glycyrrhiza uralensis Fisch. (GC) is widely utilized in traditional Chinese medicine (TCM) for its properties in Qi tonification, heat clearing, and detoxification. Within TCM theory, Qi is also implicated in tumor development. Numerous TCM formulas containing GC are used for their anti-tumor effects, and contemporary pharmacological research has demonstrated that ethyl acetate extracts (EAe) of GC, along with potential bioactive compounds like glabridin (Gla), possess anti-tumor properties. Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and a major challenge to global healthcare, with high incidence and poor prognosis. Nevertheless, the effects and mechanisms of action of Gla in inhibiting HCC have not been extensively studied.

Aim of study: This study aims to elucidate the effects and mechanisms of action of Gla against HCC by in vitro and in vivo experiments.

Methods: The inhibitory effects of ethyl acetate extract (EAe) of GC and its bioactive compounds on HCC were studied using a drug-cell interaction system equipped with UPLC-MS/MS and high-throughput screening methods in vitro. RNA sequencing (RNA-seq) and bioinformatics technologies were employed to detect the differentially expressed genes (DEGs) and pathways in HepG2 cells. The findings were further validated using quantitative real-time PCR (qPCR) and Western blot (WB) assays. Additionally, an in vivo tumor-bearing mouse model established with H22 cells was utilized to examine alterations in tumor tissues via hematoxylin-eosin (HE) staining. Immunohistochemistry was used to assess the protein expression levels of hub targets within each group.

Results: Both in vitro and in vivo experiments demonstrated the effects of EAe against HCC, identifying Gla was one of its main bioactive compounds. Integration of RNA-seq data with clinical databases revealed that Gla inhibited HCC by up-regulating the expression levels of DUSP5, ZFP36, KLF10, and NR4A1, while down-regulating RMI2 expression. These findings were further validated by Gene Expression Omnibus (GEO), qPCR, WB and immunohistochemistry assays.

Conclusions: Gla regulates the expression levels of DUSP5, ZFP36, KLF10, NR4A1, and RMI2 to against HCC, providing valuable insights for the application of Gla in HCC treatment.

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格拉布林通过调节多靶点抑制肝细胞癌的增殖和迁移

民族药理学意义：甘草（Glycyrrhiza uralensis Fisch.(Glycyrrhiza uralensis Fisch）具有补气、清热和解毒的功效，在传统中医学中被广泛使用。在中医理论中，气也与肿瘤的发展有关。许多含有 GC 的中药配方都具有抗肿瘤作用，当代药理学研究表明，GC 的乙酸乙酯提取物（EAe）以及潜在的生物活性化合物如格罗布定（Gla）具有抗肿瘤特性。肝细胞癌（HCC）发病率高、预后差，是全球第六大常见癌症，也是全球医疗保健面临的一大挑战。然而，格拉抑制 HCC 的效果和作用机制尚未得到广泛研究：本研究旨在通过体外和体内实验阐明 Gla 对 HCC 的作用效果和机制：方法：采用配备UPLC-MS/MS的药物-细胞相互作用系统和高通量筛选方法，在体外研究GC的乙酸乙酯提取物（EAe）及其生物活性化合物对HCC的抑制作用。采用 RNA 测序（RNA-seq）和生物信息学技术检测了 HepG2 细胞中的差异表达基因（DEGs）和通路。研究结果通过定量实时 PCR（qPCR）和 Western 印迹（WB）检测得到了进一步验证。此外，还利用 H22 细胞建立的体内肿瘤小鼠模型，通过苏木精-伊红（HE）染色检查肿瘤组织的变化。免疫组织化学法用于评估各组中枢靶标的蛋白表达水平：体外和体内实验都证明了EAe对HCC的作用，并确定Gla是其主要生物活性化合物之一。RNA-seq数据与临床数据库的整合显示，Gla通过上调DUSP5、ZFP36、KLF10和NR4A1的表达水平，同时下调RMI2的表达来抑制HCC。基因表达总库（GEO）、qPCR、WB和免疫组化检测进一步验证了这些发现：结论：Gla 可调节 DUSP5、ZFP36、KLF10、NR4A1 和 RMI2 的表达水平，从而对抗 HCC，为 Gla 在 HCC 治疗中的应用提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.