Ginsenoside Rd alleviates atherosclerosis by inhibiting adipocyte ferroptosis in perivascular adipose tissues
- 1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, PR China; Corresponding author. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, No.1, Longhu Middle Ring Road, Jinshui District, Zhengzhou, 450000, Henan, PR China.
- 2Department of Comprehensiveness, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, PR China
- 3Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, PR China
Abstract
Background: Ginsenoside Rd (Rd) is an active ingredient in Panax ginseng Meyer and can be absorbed into the adipose tissue. Here, we aimed to investigate the impact of Rd on atherosclerosis (AS) and explore the mechanism. Methods: We constructed an AS model by feeding ApoE -/- mice with a standard Western high-fat diet, treated with Rd, and combined RORC and TIGAR adipocyte-specific adeno-associated virus infection. An inflammatory adipocyte model (3T3-L1) was induced by LPS, and a lipid accumulation model in adipocytes was induced by palmitic acid. We investigated the role of the Rd-mediated RORC/TIGAR axis in adipocyte inflammation, oxidative stress, and ferroptosis through lentiviral vectors and the ferroptosis activator erastin. The interactions between RORC and TIGAR were examined. Next, the degree of lipid peroxidation and ferroptosis within perivascular adipose tissues (PVAT) in mice and 3T3-L1 cells was assessed. Results: Rd improved PVAT dysfunction and alleviated endothelial inflammation in AS mice. Rd targeted and inhibited RORC expression in adipocytes within the PVAT of mice. The transcription factor RORC occupied the TIGAR promoter to repress TIGAR transcription. Reactivation of RORC reversed the therapeutic benefit of Rd on AS, and reactivation of TIGAR also alleviated AS exacerbated by RORC. Rd reached therapeutic benefits by inhibiting RORC expression in adipocytes within PVAT, weakening its inhibitory effect on TIGAR, and further inhibiting adipocyte ferroptosis. Conclusion: Rd targets RORC to activate TIGAR expression and block adipocyte ferroptosis in PVAT, thereby inhibiting AS.
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BibTeX
@article{fu2026ginsenoside,
title = {{Ginsenoside Rd alleviates atherosclerosis by inhibiting adipocyte ferroptosis in perivascular adipose tissues}},
author = {Xin Fu and Chuang Liu and Fudong Hu and Jielin Qin and Tingting Wang and Xiaoke Li},
journal = {Journal of Ginseng Research},
year = {2026},
month = aug,
doi = {10.1016/j.jgr.2026.101150},
url = {https://doi.org/10.1016/j.jgr.2026.101150},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ginsenoside Rd alleviates atherosclerosis by inhibiting adipocyte ferroptosis in perivascular adipose tissues
AU - Xin Fu
AU - Chuang Liu
AU - Fudong Hu
AU - Jielin Qin
AU - Tingting Wang
AU - Xiaoke Li
PY - 2026
DA - 2026/08/31
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101150
UR - https://doi.org/10.1016/j.jgr.2026.101150
AB - Background: Ginsenoside Rd (Rd) is an active ingredient in Panax ginseng Meyer and can be absorbed into the adipose tissue. Here, we aimed to investigate the impact of Rd on atherosclerosis (AS) and explore the mechanism. Methods: We constructed an AS model by feeding ApoE -/- mice with a standard Western high-fat diet, treated with Rd, and combined RORC and TIGAR adipocyte-specific adeno-associated virus infection. An inflammatory adipocyte model (3T3-L1) was induced by LPS, and a lipid accumulation model in adipocytes was induced by palmitic acid. We investigated the role of the Rd-mediated RORC/TIGAR axis in adipocyte inflammation, oxidative stress, and ferroptosis through lentiviral vectors and the ferroptosis activator erastin. The interactions between RORC and TIGAR were examined. Next, the degree of lipid peroxidation and ferroptosis within perivascular adipose tissues (PVAT) in mice and 3T3-L1 cells was assessed. Results: Rd improved PVAT dysfunction and alleviated endothelial inflammation in AS mice. Rd targeted and inhibited RORC expression in adipocytes within the PVAT of mice. The transcription factor RORC occupied the TIGAR promoter to repress TIGAR transcription. Reactivation of RORC reversed the therapeutic benefit of Rd on AS, and reactivation of TIGAR also alleviated AS exacerbated by RORC. Rd reached therapeutic benefits by inhibiting RORC expression in adipocytes within PVAT, weakening its inhibitory effect on TIGAR, and further inhibiting adipocyte ferroptosis. Conclusion: Rd targets RORC to activate TIGAR expression and block adipocyte ferroptosis in PVAT, thereby inhibiting AS.
SN - 1226-8453
SN - 2093-4947
ER -