Publications related to genipin used for liver diseases control
Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis
Inchin-ko-to (TJ-135) is an herbal medicine used in Japan for treatment of icteric patients with cirrhosis. Its efficacy as an anti-fibrogenic drug was evaluated in relation to stellate cell activation.
You may have read about mice being used to study complex human diseases. This is because some diseases are shared by humans and mice. When scientists do their research on mice it gives them insights on the risk factors of the disease among the humans. The site here lets you know about some clinical trials that were done on mice.
Liver fibrosis was induced in rats by repeated injections of carbon tetrachloride (CCl4) or pig-serum. Oral administration of TJ-135 improved the mortality of rats given CCl4 with reduced extents of liver necrosis and fibrosis. Similar improvement of liver fibrosis was found in rats given pig-serum showing no liver necrosis.
DNA synthesis of stellate cells activated in vitro after isolation from normal rat liver was decreased by culture with TJ-135 in a dose-related manner, accompanied by decreased smooth muscle Î± actin expression and contractility. Such attenuation was not found in the cells cultured with geniposide, an iridoid compound of TJ-135, but genipin, an aglycone of geniposide formed in the gut by action of bacterial flora, markedly decreased stellate cell activation without affecting synthesis of proteins other than collagen.
Source: Journal of Hepatology Volume 41, Issue 4, October 2004, Pages 584-591
Genipin derivative having liver protection activity
US Patent Issued on July 17, 2001
It has been reported that the known iridoid genipin is a natural substance, and acts as a therapeutic agent for hepatitis B through the mechanism to inhibit the HBV replication (Korean Patent Laid-open No. 94-1886).
Genipin also has some in vivo activities such as liver-protection, inhibition of biosynthesis of RNA and protein, detoxification as well as antiviral activity. Particularly, it has been disclosed that genipin is also effective as an anti-tumor agent (Japanese Patent Laid-open No. 80/164625).
Genipin, a metabolite derived from the herbal medicine Inchin-ko-to, and suppression of Fas-induced lethal liver apoptosis in mice.
It has been shown previously that a Kampo (Chinese/Japanese herbal) medicine, Inchin-ko-to (ICKT), inhibits hepatocyte apoptosis induced by transforming growth factor beta1 in vitro. The present study investigated whether ICKT or its ingredients inhibit Fas-mediated liver apoptosis in vivo. METHODS: Acute liver injury was induced by an intravenous injection of anti-Fas antibody, Jo2. The effects of ICKT and its ingredients on lethality, histology, apoptotic index, serum transaminase levels, caspase activation, mitochondrial membrane potential (Deltapsi(m)), and mitochondrial permeability transition (MPT) were analyzed. Apoptosis in mouse hepatocytes in vitro was also evaluated. RESULTS: Pretreatment with ICKT rescued 75% of Jo2-treated mice and markedly suppressed liver apoptosis/injury. Genipin, an intestinal bacterial metabolite of geniposide that is a major ingredient of ICKT, was found to be an active principle of ICKT. Genipin also suppressed in vitro Fas-mediated apoptosis in primary-cultured murine hepatocytes. Activation of caspase 3 and 8 in the liver homogenate and rapid reduction of triangle uppsi(m) of hepatocytes isolated from Jo2-treated mice were inhibited by genipin preadministration. The resistance to Ca(2+)-induced MPT was enhanced in liver mitochondria of genipin-treated mice. CONCLUSIONS: These results suggest that the antiapoptotic activity of genipin via the interference with MPT is a possible mechanism for therapeutic effects of ICKT.
Source: Kampo Pharmacology Department, Tsumura Central Research Laboratories, Tsumura & Co., Ibaraki, Japan. PMID: 10648466
Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver
Inchin-ko-to (ICKT), an herbal medicine, and its ingredients exert potent choleretic effects by a bile acid-independent mechanism. The current study was designed to determine whether ICKT or its ingredients potentiate multidrug resistance-associated protein 2 (Mrp2; Abcc2)-mediated choleresis in vivo. Biliary secretion of Mrp2 substrates and the protein mass, subcellular localization, and messenger RNA (mRNA) level of Mrp2 were assessed in rat liver after infusion of genipin, an intestinal bacterial metabolite of geniposide, a major ingredient of ICKT. The function of Mrp2 was also assessed by the adenosine triphosphate (ATP)-dependent uptake of Mrp2-specific substrates using canalicular membrane vesicles (CMVs) from the liver. Infusion of genipin increased bile flow by 230%. It also increased biliary secretion of bilirubin conjugates and reduced glutathione (GSH) by 513% and 336%, respectively, but did not increase bile acid secretion. The ATP-dependent uptake of estradiol 17–D-glucuronide (E217G; by 265%), leukotriene C4 (LTC4; by 161%), taurolithocholate-3-sulfate (TLC-3S; by 266%), and methotrexate (MTX; by 234%) was significantly stimulated in the CMVs from the liver. These effects were not observed in Mrp2-deficient rats. Under these conditions, genipin treatment increased the protein mass of Mrp2 in the CMVs but not the mRNA level. In immunoelectron microscopic studies, a marked increase in Mrp2 density in the canalicular membrane (CM) and microvilli was observed in the genipin-treated liver tissue sections when compared with the vehicle-treated liver tissue sections. In conclusion, genipin may enhance the bile acid-independent secretory capacity of hepatocytes, mainly by stimulation of exocytosis and insertion of Mrp2 in the bile canaliculi. ICKT may be a potent therapeutic agent for a number of cholestatic liver diseases.
Source: HEPATOLOGY 2004;39:167-178.
Genipin prevents fulminant hepatic failure resulting in reduction of lethality through the suppression of TNF-Î± production
Genipin is a metabolite derived from the herbal medicine Inchinko-to. Little is known about the mechanism of genipin action on acute liver injury through inflammatory cytokines. We examined the effects of genipin on production of TNF-Î± in vivo and in vitro. Mice were given GalN/LPS with or without genipin treatment. All mice not given genipin died within 12 h. But in mice given genipin, 8 of 15 mice survived for 24 h after GalN/LPS administration. Histologically, hepatic necrosis and inflammatory cells infiltration were significantly slight in mice given genipin. Serum AST and ALT activity were significantly lower in mice given genipin. Serum and liver homogenate TNF-Î± levels were significantly lower in mice given genipin. However, in IL-6 and IL-1Î², there were no significant differences in mice given and not given genipin. TNF-Î±, NF-ÎºB activation and TNF-Î± mRNA expression in a cultured mouse macrophage-like cell line J774.1 were significantly suppressed by genipin administration. In conclusion, the present findings suggest that genipin, a metabolite derived form the herbal medicine Inchinko-to improved acute liver dysfunction by suppressive effect of TNF-Î± production.