Ginsenoside Rg1 alleviates lupus nephritis by inhibiting complement activation in MRL/lpr mice

Lupus nephritis (LN) is a major cause of kidney damage in patients with systemic lupus erythematosus (SLE). This study evaluates the therapeutic effects of ginsenoside Rg1, a bioactive ginseng compound, with emphasis on its regulation of complement activation in LN. MRL/lpr mice were divided into model and Rg1-treated groups(50 or 100 mg/kg/day) for 5 weeks, while C57BL/6J mice served as normal controls. Renal function, autoantibody levels, and histopathological changes were analyzed. The expression of complement components (CFB, C3, C5, C5b-9) were analyzed by Western blotting and immunohistochemistry. A correlation analysis was performed to evaluate the relationship between renal C5b-9 deposition and proteinuria. Rg1 treatment significantly alleviated clinical symptoms, including weight loss and skin lesions. It also induced a dose-dependent improvement in renal function, as evidenced by reduced proteinuria (0.15 ± 0.03 g/L vs. 1.20 ± 1.09 g/L), serum creatinine (8.1 ± 0.7 μmol/L vs. 13.4 ± 2.2 μmol/L), and urea (7.07 ± 1.13 mmol/L vs. 12.46 ± 4.14 mmol/L). Histopathological evaluation revealed attenuated glomerular inflammation, decreased immune complex deposition, and improved renal architecture. Mechanistically, Rg1 modulated the alternative complement pathway, leading to a significant reduction of the terminal membrane attack complex (C5b-9), which strongly correlated with the amelioration of proteinuria (r = 0.79, p < 0.01), alongside complex changes in upstream components including CFB and C3. Ginsenoside Rg1 effectively mitigates renal injury in LN by suppressing complement activation, particularly via inhibition of the alternative pathway, thereby reducing immune complex-mediated damage. These findings suggest its potential as an adjunct therapeutic candidate for the management of LN.