Effects of the Japanese herbal medicine ‘Inchinko-to’ (TJ-135) on concanavalin A-induced hepatitis in mice

Abstract

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.

The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats

“…We decided the applied dose of ICKT referring from Yamashiki et al and Imanishi et al [5,12] reports. We prescribed pure extract ICKT (TJ-135).…”

“…The daily amount of ICKT is 7.5 g/day in adults. Seven and one-half grams of this product contain 1.5 g of dried extract obtained from mixed raw herbs in the following ratio: 4.0 g of Inchinko (Artemisia Capillaries Spike), 3.0 g of San-shishi (JP Gardenia Fruit), and 1.0 g of Daio (JP Rhubarb Rhizome) [5][6][7][8].…”

“…Recently, ICKT also has been reported to ameliorate concanavalin A-induced hepatitis by inhibiting the production of inflammatory cytokines [5], through the inhibition of liver cell apoptosis induced by Fas-mediated lethal liver injury [17] and TGF-beta1 [4]. TGF-beta1 is regarded as an undesirable factor in various liver disorders, because this cytokine induces fibrosis in liver tissue and the growth suppression of hepatocytes, which may worsen liver function.…”

“…The herbal medicine Inchinko-to (ICKT) has been commonly used in Japan as an anti-inflammatory, antipyretic, choleretic, and diuretic agent for liver disorders and jaundice [1][2][3]. Recently, ICKT has been reported to have a potent inhibitory effect on hepatocyte apoptosis, induced by transforming growth factor-beta 1 (TGF-beta1), and it inhibits the production of inflammatory cytokines in concanavalin A-induced hepatitis [4,5]. Furthermore, ICKT has been reported to directly suppress liver fibrosis in vivo [6,7].…”

Efficacy of Inchinkoto for Liver Cirrhosis in an Infant with Down Syndrome Complicated by Transient Myeloproliferative Disorder

“…Iinuma, et al reported that Inchinkoto might have a protective and antifibrotic effect for the liver of children with biliary atresia [6] [7]. Though the precise mechanisms of its action on the liver diseases remain unknown, it can be speculated as following: 1) inhibition of hepatocyte apoptosis induced by transforming growth factor-β1 [10]; 2) inhibition of the production of inflammatory cytokines and inducible nitric oxide synthase [11] [12]; and 3) direct suppression of liver fibrosis [13]. Despite the promising effects on diverse liver diseases without serious adverse effects, to the best of our knowledge, Inchinkoto has not previously been given to patients with LC characterized by diffuse nodular regeneration surrounded by fibrous bands [14].…”