The Protective Effect of Esculentoside A on MPL/lpr Mice by Upregulating the Expression of CD19+IL-35+Breg Cells and Interleukin-35

Introduction: Esculentoside A (EsA) is one of the main components of the traditional Chinese medicine Phytolacca esculenta. The possible mechanism of action of EsA in the treatment of lupus nephritis (LN) was explored by observing the effects of EsA on CD19+ IL-35+regulatory B (IL-35+Breg) cells. Methods: Twenty-four MRL/lpr mice were randomly divided into control, EsA, and EsA+IL-12p35 antibody groups. Mice were administered the respective treatments intraperitoneally once a day for 4 weeks. The urine protein/creatinine ratio (UPCR) and blood creatinine (Cr) and IL-35, IL-10, and IL-17 expression levels were measured. Body and spleen weight were measured to calculate the splenic index (SI). Flow cytometry was performed to determine the proportion of CD19+ IL-35+ Breg cells in the spleen. Hematoxylin-eosin and PASM-Masson staining of renal tissues were performed, and the “Austin” acute index (AI) system for LN was determined. Results: The most severe conditions were seen in mice in the control group, with the highest UPCR, Cr, and IL-17 levels and SI and AI scores; the most severe renal histopathology, and the lowest proportion of CD19+ IL-35+ Breg cells and IL-35 and IL-10 levels. This was followed by the EsA+IL-12p35 antibody group. The EsA group had the lowest UPCR, Cr, and IL-17 levels and SI and AI scores; the mildest renal lesions; and the highest proportion CD19+ IL-35+ Breg cells and IL-35 and IL-10 levels. Conclusion: EsA delayed the progression of LN by promoting the proliferation of CD19+ IL-35+ Breg cells, upregulating the expression of IL-35, and decreasing the secretion of IL-17.