Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Reciprocal regulation of SIRT1 and AMPK by Ginsenoside compound K impedes the conversion from plasma cells to mitigate for podocyte injury in MRL/lpr mice in a B cell-specific manner

  • Ziyu Song (First School of Clinical Medicine, Zhejiang Chinese Medical University) ;
  • Meng Jin (First School of Clinical Medicine, Zhejiang Chinese Medical University) ;
  • Shenglong Wang (First School of Clinical Medicine, Zhejiang Chinese Medical University) ;
  • Yanzuo Wu (First School of Clinical Medicine, Zhejiang Chinese Medical University) ;
  • Qi Huang (Department of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medical University) ;
  • Wangda Xu (First School of Clinical Medicine, Zhejiang Chinese Medical University) ;
  • Yongsheng Fan (College of Basic Medical Science, Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University) ;
  • Fengyuan Tian (First School of Clinical Medicine, Zhejiang Chinese Medical University)
  • Received : 2023.06.28
  • Accepted : 2023.11.28
  • Published : 2024.03.01
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Abstract

Background: Deposition of immune complexes drives podocyte injury acting in the initial phase of lupus nephritis (LN), a process mediated by B cell involvement. Accordingly, targeting B cell subsets represents a potential therapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possesses nephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulations remain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed by measurements of anti-dsDNA antibodies, inflammatory chemokines, and metabolite profiles on renal samples. Podocyte function and ultrastructure were detected. Publicly available single-cell RNA sequencing data and flow cytometry analysis were employed to investigate B cell subpopulations. Metabolomics analysis was adopted. SIRT1 and AMPK expression were analyzed by immunoblotting and immunofluorescence assays. Results: CK reduced proteinuria and protected podocyte ultrastructure in MRL/lpr mice by suppressing circulating anti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK with Rhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated the resolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstating podocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restoration of renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocyte function. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity of renal B cell subsets during LN.

Keywords

Acknowledgement

The authors thank Betty Diamond for sharing the duplicate extraction in the single-cell genomics data. This work was supported by the Project of Zhejiang Provincial Administration of Traditional Chinese Medicine (2020ZZ009, 2021ZX005), the Advantage Discipline Construction Project from Zhejiang Provincial Hospital of Traditional Chinese Medicine (2D02311), the Tangjun Famous Traditional Chinese Medicine Doctor Inherit Workstation Project of Zhejiang Province of China (GZS2021021), and the Huangqi Famous Traditional Chinese Medicine Doctor Inherit Workstation Project of Zhejiang Province of China (GZS2020021).

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