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 10mg/kg, 20mg/kg, 40 mg/kg or 80 cmg/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-gamma 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 G(0)+G(1) 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 20mg/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 G(0)+G(1) phase, and caused possibly by mechanisms associated with metabolic activation.
Jeon
Tae Won
TW
College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, South Korea. taecheon@yumail.ac.kr
Jin
Chun Hua
CH
Lee
Sang Kyu
SK
Jun
In Hye
IH
Kim
Ghee Hwan
GH
Lee
Dong Ju
DJ
Jeong
Hye Gwang
HG
Lee
Kyung-Bok
KB
Jahng
Yurngdong
Y
Jeong
Tae Cheon
TC
D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007165:Immunosuppression Therapy; D026121:Indole Alkaloids; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D011799:Quinazolines; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D014665:Vasodilator Agents / Q000633:toxicity*; D052999:Quinazolinones
D000470:Alkaloids; D026121:Indole Alkaloids; D007376:Interleukin-2; D011799:Quinazolines; D014665:Vasodilator Agents; C028632:rutecarpine; D052999:Quinazolinones