Ginseng-containing Shentao Ruangan (STR) formula alleviates hepatic fibrosis via hepatocellular Nrf2-ROS-TGF-β axis regulating hepatocyte-HSC crosstalk: Integrating single-cell RNA sequencing and multi-tiered validation

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-07-01 Epub Date: 2026-05-07 DOI:10.1016/j.jgr.2026.101053

Shangyi Huang, Ruisheng Zhou, Jing Li, Yi Zheng, Lunwei Yang, Tianqi Gao, Yi Yuan, Dailin Wu, Yafei Shi, Dayong Zheng, Daihan Zhou, Ying Tang

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引用次数: 0

Abstract

Background

The ginseng-containing Shentao Ruangan (STR) formula is clinically used for chronic liver conditions, including hepatic fibrosis. Guided by traditional Chinese medicine (TCM) principles, it targets the “deficiency leading to accumulation (Xu Sun Sheng Ji)" pathology in hepatic fibrosis via the “strengthening healthy qi and dispelling pathogenic factors (Fu Zheng Qu Xie)" mechanism.

Aims

To elucidate how STR attenuates hepatic fibrosis, focusing on its regulation of the fibrotic liver microenvironment.

Methods

Single-cell RNA sequencing profiled the fibrotic liver microenvironment; GEO analysis confirmed reactive oxygen species (ROS) as a central fibrotic driver. In vitro/in vivo experiments assessed STR's effects on ROS and fibrosis. Mechanisms were explored via RNA sequencing, network pharmacology, molecular docking, Nrf2 inhibitors and Nrf2-knockout (Nrf2^−/−) mice.

Results

Single-cell sequencing identified hepatocyte-hepatic stellate cell (HSC) crosstalk as a core fibrotic feature, with hepatocellular metabolic dysfunction and elevated ROS promoting fibrosis (GEO-validated). STR alleviated fibrosis and suppressed excessive hepatic ROS in vitro and in vivo. Integrated analyses identified ROS modulation as STR's key anti-fibrotic mechanism, with Nrf2 as the critical target. STR activated hepatocellular Nrf2, alleviating oxidative stress, reducing TGF-β expression and secretion, and thus inhibiting HSC activation and extracellular matrix deposition. Molecular docking, Nrf2 inhibitors and Nrf2^−/− mouse studies confirmed Nrf2's essential role.

Conclusion

This study links hepatocyte-HSC crosstalk/ROS-TGF-β-driven activation in hepatic fibrosis to TCM's “Xu Sun Sheng Ji”, while STR's Nrf2-mediated antioxidant and anti-fibrotic actions embody “Fu Zheng Qu Xie”, integrating TCM with modern medicine. STR, a ginseng-containing formula, is a promising targeted fibrosis therapy, advancing TCM-modern medicine integration.

Abstract Image

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参桃软肝方通过肝细胞Nrf2-ROS-TGF-β轴调控肝细胞- hsc串扰减轻肝纤维化：整合单细胞RNA测序和多层验证

背景：参道软肝方在临床上用于治疗慢性肝病，包括肝纤维化。它以中医原理为指导，通过“扶正祛邪”的机制，针对肝纤维化的“虚生积”病理。目的：探讨STR对肝纤维化微环境的调节作用，探讨其对肝纤维化的影响。方法：单细胞RNA测序分析纤维化肝微环境；GEO分析证实活性氧（ROS）是纤维化的主要驱动因素。体外/体内实验评估了STR对ROS和纤维化的影响。通过RNA测序、网络药理学、分子对接、Nrf2抑制剂和Nrf2敲除（Nrf2-/-）小鼠探索机制。结果：单细胞测序鉴定肝细胞-肝星状细胞（HSC）串扰是纤维化的核心特征，肝细胞代谢功能障碍和ROS升高促进纤维化（geo验证）。STR在体外和体内均能减轻纤维化，抑制过量的肝脏ROS。综合分析发现ROS调节是STR的关键抗纤维化机制，而Nrf2是关键靶点。STR激活肝细胞Nrf2，减轻氧化应激，降低TGF-β的表达和分泌，从而抑制HSC活化和细胞外基质沉积。分子对接、Nrf2抑制剂和Nrf2-/-小鼠研究证实了Nrf2的重要作用。结论：本研究将肝纤维化中肝细胞- hsc串扰/ROS-TGF-β驱动的活化与中医的“徐孙生机”联系起来，而STR的nrf2介导的抗氧化、抗纤维化作用体现了“扶正祛泻”，是中医与现代医学的结合。参方STR是一种很有前景的纤维化靶向治疗药物，促进了中西医结合。

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来源期刊

Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE

CiteScore

11.40

自引率

9.50%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.