Drug Design, Development and Therapy (Apr 2024)
Sinomenine Hydrochloride Protects IgA Nephropathy Through Regulating Cell Growth and Apoptosis of T and B Lymphocytes
Abstract
Jun-Jian Li,1,2,* Li Li,2,* Shuang Li,2,3 Xin-Yi Tang,2 Hui-Feng Sun,1 Jian-Xin Liu2 1School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2School of Pharmaceutical Sciences, School of Basic Medical Sciences, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, People’s Republic of China; 3Harbin Voolga Technology Co., Ltd., Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui-Feng Sun, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People’s Republic of China, Email [email protected] Jian-Xin Liu, School of Pharmaceutical Sciences, School of Basic Medical Sciences, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine, Huaihua, 41800, People’s Republic of China, Fax +745-2381210, Email [email protected]: 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
