Ginsenoside CK potentiates SIRT1 to alleviate lupus nephritis through compensating for XBP1-mediated endoplasmic reticulum stress in plasma cells.
10.1016/j.jpha.2025.101245
- Author:
Ziyu SONG
1
;
Ying LI
2
;
Sumei XU
1
;
Shuowen QIAN
2
;
Wangda XU
3
;
Li XU
4
;
Fengyuan TIAN
1
Author Information
1. General Practice, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, China.
2. First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310000, China.
3. Department of Endocrinology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310000, China.
4. College of Basic Medical Science, Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310000, China.
- Publication Type:Journal Article
- Keywords:
Endoplasmic reticulum stress;
Ginsenoside compound K;
Lupus nephritis;
Plasma cell;
Sirtuins
- From:
Journal of Pharmaceutical Analysis
2025;15(10):101245-101245
- CountryChina
- Language:English
-
Abstract:
Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis (LN), and targeting plasma cell aggregation offers a promising therapeutic strategy. Ginsenoside compound K (i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol) (CK), a derivative of ginsenoside, has indicated significant potential in alleviating renal damage in lupus-prone mice, potentially by modulating B cell dynamics in response to endoplasmic reticulum (ER) stress. In this study, CK (20 or 40 mg/kg) was orally administered to female MRL/lpr mice for 10 weeks. The effects of CK on B cell subpopulations, renal function, and histopathological changes were evaluated. Single-cell ribonucleic acid sequencing was employed to analyze gene expression profile and pseudotime trajectories during B cell-mediated renal injury. Additionally, in vitro B cell assays were conducted to explore the role of the sirtuin-1 (SIRT1)-X-box binding protein 1 (XBP1) axis in ER stress. Our findings demonstrated that CK effectively reduced anti-double stranded DNA (dsDNA) antibody levels, alleviated systemic inflammation, improved renal function, and facilitated the clearance of deposited immune complexes. CK likely suppressed the unfolded protein response (UPR), delaying the differentiation of renal-activated B cells into plasma cells. It promoted B cell-specific SIRT1 activation and inhibited the splicing of XBP1 into its active form, XBP1s. CK also restored ER morphology by interacting with calmodulin (CALM) to maintain ER calcium storage, reinforcing SIRT1 functional integrity and promoting XBP1 deacetylation, thereby limiting plasma cell differentiation. In conclusion, CK mitigates plasma cell accumulation in the renal microenvironment by preventing SIRT1-mediated XBP1 splicing, offering a potential therapeutic approach for LN.
