Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis

doi:10.1016/j.jpha.2023.11.009

科研成果详情

题名	Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis
作者	Lin, Lifan1; Li, Xinmiao 1; Li, Yifei 1; Lang, Zhichao1; Li, Yeping2; Zheng, Jianjian3
发表日期	2024-05-01
发表期刊	Journal of Pharmaceutical Analysis; 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Ferroptosis Ginsenoside Rb1 Hepatic stellate cells Liver fibrosis
其他关键词	ACTIVATION
摘要	Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), a process associated with ferroptosis. Ginsenoside Rb1 (GRb1), a major active component extracted from Panax ginseng, inhibits HSC activation. However, the potential role of GRb1 in mediating HSC ferroptosis remains unclear. This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro, using CCl4-induced liver fibrosis mouse model and primary HSCs, LX-2 cells. The findings revealed that GRb1 effectively inactivated HSCs in vitro, reducing alpha-smooth muscle actin (α-SMA) and Type I collagen (Col1A1) levels. Moreover, GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo. From a mechanistic standpoint, the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1. Specifically, GRb1 promoted HSC ferroptosis both in vivo and in vitro, characterized by increased glutathione depletion, malondialdehyde production, iron overload, and accumulation of reactive oxygen species (ROS). Intriguingly, GRb1 increased Beclin 1 (BECN1) levels and decreased the System Xc-key subunit SLC7A11. Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1. Moreover, BECN1 could directly interact with SLC7A11, initiating HSC ferroptosis. In conclusion, the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro. Overall, this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation, at least partly through its modulation of BECN1 and SLC7A11.
资助项目	Wenzhou Municipal Science and technology Bureau[Y20220023];Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province[2022E10022];Wenzhou Medical University[KYYW201904];
出版者	Xi'an Jiaotong University
ISSN	2095-1779
EISSN	2214-0883
卷号	14 期号:5 页码:744-757
DOI	10.1016/j.jpha.2023.11.009
页数	14
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001243412600001
收录类别	SCOPUS ; PUBMED ; SCIE ; 万方 ; CSCD
URL	查看原文
PubMed ID	38784156
SCOPUSEID	2-s2.0-85188538905
通讯作者地址	[Zheng, Jianjian]Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China ; [Li, Yeping]Department of Urology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
Scopus学科分类	Analytical Chemistry;Pharmacy;Pharmaceutical Science;Drug Discovery;Spectroscopy;Electrochemistry
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/213341
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院
通讯作者	Li, Yeping; Zheng, Jianjian
作者单位	1.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 2.Department of Urology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 3.Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Lin, Lifan,Li, Xinmiao,Li, Yifei,et al. Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis[J]. Journal of Pharmaceutical Analysis;,2024,14(5):744-757.
APA	Lin, Lifan, Li, Xinmiao, Li, Yifei, Lang, Zhichao, Li, Yeping, & Zheng, Jianjian. (2024). Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis. Journal of Pharmaceutical Analysis;, 14(5), 744-757.
MLA	Lin, Lifan,et al."Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis".Journal of Pharmaceutical Analysis; 14.5(2024):744-757.