Effects of the Japanese herbal medicine 'Inchinko-to' (TJ-135) on concanavalin A-induced hepatitis in mice.
Inchinko-to (TJ-135) is a herbal medicine consisting of three kinds of crude drugs, and in Japan it is administered mainly to patients with cholestasis. The present study evaluated the effects of TJ-135 on concanavalin A (con A)-induced hepatitis in mice in vivo and con A-induced cytokine production in vitro. When mice were pretreated with oral TJ-135 for 1 week before intravenous con A injection, the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly decreased 8 h after con A administration (-82%, -96% and -66% respectively). In histological investigations, sub-massive hepatic necrosis accompanying inflammatory cell infiltration was not observed in mice pretreated with TJ-135. Serum levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and IL-2 were significantly lower in mice pretreated with TJ-135 compared with controls, while IL-10 levels were higher in these mice. Intrasplenic IL-12 levels were significantly lower in mice pretreated with TJ-135, while intrasplenic IL-10 levels were higher in these mice. In vitro, IL-10 production by splenocytes was increased by the addition of TJ-135 to the culture medium, whereas the production of IL-12 and IFN-gamma was inhibited. These results suggest that con A-induced hepatitis was ameliorated by pretreatment with TJ-135. With regard to the mechanism of these effects of TJ-135, we speculate that TJ-135 inhibits the production of inflammatory cytokine and enhances the production of anti-inflammatory cytokines. Therefore administration of TJ-135 may be useful in patients with severe acute hepatitis accompanying cholestasis or in those with autoimmune hepatitis.
Yamashiki
M
M
Department of Laboratory Medicine, Mie University School of Medicine, Tsu, Mie, Japan. yamashik@clin.medic.mie-u.ac.jp
Mase
A
A
Arai
I
I
Huang
X X
XX
Nobori
T
T
Nishimura
A
A
Sakaguchi
S
S
Inoue
K
K
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology; D003208:Concanavalin A / Q000633:toxicity*; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood / Q000502:physiology; D018664:Interleukin-12 / Q000097:blood / Q000502:physiology; D007376:Interleukin-2 / Q000097:blood / Q000502:physiology; D007564:Japan; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D008297:Male; D008518:Medicine, East Asian Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D037121:Plant Lectins; D010946:Plants, Medicinal / Q000502:physiology*
D007376:Interleukin-2; D037121:Plant Lectins; D003208:Concanavalin A; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase