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 cellspecifi c manner

• Published in: Journal of ginseng research 2024, 48(2), , pp.190-201
• Main Authors: Ziyu Song, Meng Jin, Shenglong Wang, Yanzuo Wu, Qi Huang, Wangda Xu, Yongsheng Fan, Fengyuan Tian
• Format: Article
• Language: English
• Subjects: 기타의약학
• ISSN: 1226-8453; 2093-4947
• DOI: 10.1016/j.jgr.2023.11.006

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 potentialtherapeutic approach for LN. Ginsenoside compound K (CK), a bioavailable component of ginseng, possessesnephritis benefits in lupus-prone mice; however, the underlying mechanisms involving B cell subpopulationsremain elusive. Methods: Female MRL/lpr mice were administered CK (40 mg/kg) intragastrically for 10 weeks, followed bymeasurements 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 flowcytometry 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 circulatinganti-dsDNA antibodies and mitigating systemic inflammation. It activated B cell-specific SIRT1 and AMPK withRhamnose accumulation, hindering the conversion of renal B cells into plasma cells. This cascade facilitated theresolution of local renal inflammation. CK facilitated the clearance of deposited immune complexes, thus reinstatingpodocyte morphology and mobility by normalizing the expression of nephrin and SYNPO. Conclusions: Our study reveals the synergistic interplay between SIRT1 and AMPK, orchestrating the restorationof renal B cell subsets. This process effectively mitigates immune complex deposition and preserves podocytefunction. Accordingly, CK emerges as a promising therapeutic agent, potentially alleviating the hyperactivity ofrenal B cell subsets during LN. KCI Citation Count: 0