Sinomenine Hydrochloride Protects IgA Nephropathy Through Regulating Cell Growth and Apoptosis of T and B Lymphocytes

Abstract

Purpose

Sinomenine hydrochloride (SH) is used to treat chronic inflammatory diseases such as rheumatoid arthritis and may also be efficacious against Immunoglobulin A nephropathy (IgAN). However, no trial has investigated the molecular mechanism of SH on IgAN. Therefore, this study aims to investigate the effect and mechanism of SH on IgAN.

Methods

The pathological changes and IgA and C3 depositions in the kidney of an IgAN rat model were detected by periodic acid–Schiff (PAS) and direct immunofluorescence staining. After extracting T and B cells using immunomagnetic beads, we assessed their purity, cell cycle phase, and apoptosis stage through flow cytometry. Furthermore, we quantified cell cycle-related and apoptosis-associated proteins by Western blotting.

Results

SH reduced IgA and C3 depositions in stage 4 IgAN, thereby decreasing inflammatory cellular infiltration and mesangial injury in an IgAN model induced using heteroproteins. Furthermore, SH arrested the cell cycle of lymphocytes T and B from the spleen of IgAN rats. Regarding the mechanism, our results demonstrated that SH regulated the Cyclin D1 and Cyclin E1 protein levels for arresting the cell cycle and it also regulated Bax and Bcl-2 protein levels, thus increasing Cleaved caspase-3 protein levels in Jurkat T and Ramos B cells.

Conclusion

SH exerts a dual regulation on the cell cycle and apoptosis of T and B cells by controlling cell cycle-related and apoptosis-associated proteins; it also reduces inflammatory cellular infiltration and mesangial proliferation. These are the major mechanisms of SH in IgAN.

Keywords:

• sinomenine hydrochloride
• cell cycle
• apoptosis
• IgAN
• Jurkat T and Ramos B cells

Acknowledgments

This work was supported by the Hunan Province Science and Technology Innovation Key Projects (Project No: 2015SK1001, 2020SK1020), the National Natural Science Foundation of China (Project No.: 81803811, 82274178), the Wuxi Young Talent Program of Huaihua City and the Hunan University of Medicine High-Level Talent Introduction Startup Funds.

Disclosure

The authors declare no conflicts of interest in this work.