Paridis Rhizoma Saponins ameliorate CCl4-induced liver fibrosis via modulation of the Nrf2-HO-1/NQO-1 and TGF-β1/Smads signaling pathways

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-05-06 DOI:10.1016/j.bbrep.2025.102040

Yan Hong , Shuang Geng , Huihao Ao , Mengya Fu , Xiaojun Yang , Gang Cao , Yanquan Han

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引用次数: 0

Abstract

Objective/background

Paridis Rhizoma is a common traditional Chinese medicine (TCM), possessing therapeutic effects including heat-clearing, detoxification, and liver calming effects. It is frequently applied in TCM prescriptions for the treatment of liver disease. Studies have shown that total saponins derived from Paridis Rhizoma (PRS) have potent anti-liver fibrosis effect, but its mechanism in treating liver fibrosis has not been clarified. This study aimed to explore the therapeutic effect of PRS on liver fibrosis and elucidate their potential underlying pharmacological mechanisms.

Methods

The targets and pathways of Paridis Rhizoma Saponins on experimental liver fibrosis were analyzed using network pharmacology and molecular docking. PRS was administered to rats with CCL₄-induced liver fibrosis rats. Liver function, fibrosis, and inflammatory indicators were assessed using ELISA to measure serum AST and ALT, as well as liver tissue levels of HA, LN, Col IV, and PC-III fibrosis markers. Additionally, inflammatory markers IL-6, IL-β, and TNF-a were quantified. Liver morphological, H&E, and Masson's staining were used to observe the degree of liver fibrosis. The mRNA and protein expressions of Nrf2-HO-1/NQO-1 and TGF-β1/Smads signaling pathways in liver tissues were detected using immunohistochemistry (IHC) staining, Western blot (WB), and RT-qPCR.

Results

Comprehensive network pharmacology and animal experiments show that PRS may act on STAT3, SRC, VEGFA, AKT1 and other targets through its polyphyllin I, polyphyllin II, polyphyllin VI, polyphyllin VII and other components.Analysis from ELISA showed that PRS could improve liver function, mitigate the progression of liver fibrosis, and regulate inflammatory responses in rats. Morphological, H&E, and Masson's staining demonstrated that PRS significantly improved liver tissue immune response and necrosis. Additionally, IHC staining, WB results, and RT-qPCR results showed that PRS positively regulates the Nrf2-HO-1/NQO-1 and TGF-β1/Smads signaling pathways to counteract the development of pathological liver fibrosis in rats.

Conclusion

These findings indicate that PRS can mitigate the impact of CCl₄-induced liver fibrosis in experimental animals by upregulating the Nrf2-HO-1/NQO-1 and downregulating the TGF-β1/Smads signaling pathways.

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重楼皂苷通过调节Nrf2-HO-1/NQO-1和TGF-β1/Smads信号通路改善ccl4诱导的肝纤维化

目的/背景重楼根是一种常见的中药，具有清热、解毒、平肝等治疗作用。它经常被用于治疗肝病的中医处方中。研究表明，重楼总皂苷（PRS）具有较强的抗肝纤维化作用，但其治疗肝纤维化的机制尚不清楚。本研究旨在探讨PRS对肝纤维化的治疗作用，并阐明其潜在的药理机制。方法采用网络药理学和分子对接的方法，分析重楼皂苷对实验性肝纤维化的作用靶点和作用途径。ccl4诱导肝纤维化大鼠给予PRS。采用ELISA测定血清AST和ALT，以及肝组织中HA、LN、Col IV和PC-III纤维化标志物的水平，评估肝功能、纤维化和炎症指标。此外，量化炎症标志物IL-6、IL-β和TNF-a。肝形态、H&；E、Masson染色观察肝纤维化程度。采用免疫组化（IHC）染色、Western blot （WB）和RT-qPCR检测肝组织中Nrf2-HO-1/NQO-1和TGF-β1/Smads信号通路的mRNA和蛋白表达。结果综合网络药理学和动物实验表明，PRS可能通过其多叶林I、多叶林II、多叶林VI、多叶林VII等成分作用于STAT3、SRC、VEGFA、AKT1等靶点。ELISA分析显示，PRS能改善大鼠肝功能，减缓肝纤维化进程，调节炎症反应。形态学、H&；E和Masson染色显示，PRS显著改善了肝组织免疫反应和坏死。此外，IHC染色、WB结果和RT-qPCR结果显示，PRS正调控Nrf2-HO-1/NQO-1和TGF-β1/Smads信号通路，抑制大鼠病理性肝纤维化的发生。结论PRS可通过上调Nrf2-HO-1/NQO-1、下调TGF-β1/Smads信号通路，减轻ccl4诱导的实验动物肝纤维化的影响。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.