Immunosuppressive effects of rutaecarpine in female BALB/c mice

Rutaecarpine is a major quinazolinocarboline alkaloid isolated from Evodia rutaecarpa. It was reported to possess a wide spectrum of pharmacological activities, such as vasodilation, antithrombosis, and anti-inflammation. In the present study, adverse effects of rutaecarpine on immune functions were determined in female BALB/c mice. Rutaecarpine had no effects on hepatotoxicity parameters in mice, as measured by serum activities of aminotransferases. Meanwhile, rutaecarpine significantly decreased the number of antibody-forming cells and caused weight decrease in spleen in a dose-dependent manner, when mice were administered with rutaecarpine at 10 mg/kg, 20 mg/kg, 40 mg/kg or 80 mg/kg once intravenously. In addition, rutaecarpine administered mice exhibited reduced splenic cellularity, decreased numbers of total T cells, CD4⁺ cells, CD8⁺ cells, and B cells in spleen. IL-2, interferon-γ and IL-10 mRNA expressions were suppressed significantly by rutaecarpine treatment. The number of CD4⁺IL-2⁺ cells was reduced significantly following administration of mice with rutaecarpine. Furthermore, rutaecarpine caused the cell cycle arrest in G₀ + G₁ phase in a dose-dependent manner. Rutaecarpine caused significant inductions of hepatic cytochrome P450 (CYP) 1A, 2B, and 2E1 activities dose-dependently. In the splenic lymphocyte proliferation assay, rutaecarpine inhibited proliferation by LPS and Con A ex vivo, whereas it had no effects on in vitro proliferation. These results suggested that a single bolus intravenous injection of rutaecarpine from 20 mg/kg might cause immunosuppressive effects, and that rutaecarpine-induced immunosuppression might be mediated, at least in part, through the inhibition of cytokine production and cell cycle arrest in G₀ + G₁ phase, and caused possibly by mechanisms associated with metabolic activation.