curcumin and kutkin

The use of herbal drugs for the treatment of liver diseases has a long tradition in many eastern countries. The easy accessibility without the need for laborious pharmaceutical synthesis has drawn increased attention towards herbal medicines. Few herbal preparations exist as standardized extracts with major known ingredients or even as pure compounds. Some of the herbals, which show promising activity, are ellagic acid for antifibrotic treatment, phyllanthin for treating chronic hepatitis B, glycyrrhizin to treat chronic viral hepatitis and picroliv for liver regeneration. These compounds, which have proven antioxidant, antiviral or anticarcinogenic properties, can serve as primary compounds for further development as hepatoprotective drugs. This review provides the chemistry, pharmacology and future aspects of picroliv, ellagic acid and curcumin with focus on hepatoprotective properties. These phytochemicals may prove to be very useful in the treatment of hepatotoxicity induced by viral agents, toxic drugs and plant poisons. The high safety profile may be an added advantage. However, poor bioavailability and temperature and light sensitivity can reduce the efficacy of drugs like curcumin. In future, the derivatives or new combinations of these drugs may prove to be useful.

Topics: Animals; Cinnamates; Clinical Trials as Topic; Curcumin; Drug Discovery; Glycosides; Humans; Hydrolyzable Tannins; Liver; Liver Diseases; Plant Preparations; Protective Agents; Treatment Outcome; Vanillic Acid

Oxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases.

Topics: Acetaminophen; Alanine Transaminase; Alkaline Phosphatase; Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cinnamates; Curcumin; Ellagic Acid; Female; Glycosides; Lipid Peroxidation; Liver; Male; Mice; Oxidative Stress; Phytotherapy; Silymarin; Sleep; Vanillic Acid

Cadmium (Cd), a well known environmental carcinogen, is a potent immunotoxicant. In rodents, it is primarily characterized by marked thymic atrophy and splenomegaly. Cadmium induces apoptosis in murine lymphocytes and alters the immune functions. Thus, for the amelioration of its effect, three structurally different bioactive herbal extracts such as piperine-alkaloid, picroliv-glycosides and curcumin-polyphenols were evaluated and their efficacy compared. For ascertaining their immunomodulatory role, various biochemical indices of cell damage such as cytotoxicity, oxidative stress (ROS, GSH), apoptosis (mitochondrial membrane potential, caspase-3 activity, phosphatidylserine externalization, apoptotic DNA) along with lymphocyte phenotyping, blastogenesis and cytokine secretion were assessed in thymic and splenic cell suspensions. Of the three herbals examined, piperine displayed maximum efficacy. All the three doses of piperine (1, 10 and 50 microg/ml) increased cell viability in a dose dependent manner, whereas curcumin and picroliv were also effective, but to a lesser degree. Only the two higher doses exhibited cell viability efficacy. The median doses ie 10 microg/ml, were therefore selected, for comparison of their antioxidant, anti-apoptotic and immune function modulation. Restoration of ROS and GSH was most prominent with piperine. The anti-apoptotic potential was directly proportional to their antioxidant nature. In addition, Cd altered blastogenesis, T and B cell phenotypes and cytokine release were also mitigated best with piperine. The ameliorative potential was in order of piperine > curcumin > picroliv and former could be considered the drug of choice under immunocompromised conditions.

Topics: Alkaloids; Animals; Apoptosis; B-Lymphocytes; Benzodioxoles; Cadmium Chloride; Caspase 3; Cell Survival; Cinnamates; Curcumin; DNA Damage; Glutathione; Glycosides; Interferon-gamma; Interleukin-2; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Oxidative Stress; Piperidines; Polyunsaturated Alkamides; Reactive Oxygen Species; Vanillic Acid

The infection with Friend murine leukemia virus (FMuLv) is being used as a retrovirus infection model for searching the potential anti-viral medicinal preparations or establishing new treatment strategies. In the present study we have evaluated the inhibitory effect of three non-toxic antiviral natural compounds namely berberine, curcumin or picroliv against FMuLv induced erythroleukemia in BALB/c mice. To understand the effect of these compounds in the initiation and progression of leukemia we did a series of analysis, which include hematological and biochemical parameters, histopathological evaluations of the liver and the spleen and expression analysis of selected genes such as Bcl-2, p53, p45NFE2, Raf-1, Erk-1, IFNgamma receptor and erythropoietin in spleen. The treatment with berberine, curcumin or picroliv were found to (a) elevate the life span of leukemia harboring animals by more than 60 days; (b) decreased the anemic condition which was highly prevalent in FMuLv alone treated group; (c) histopathological evaluations showed that the compounds tested here inhibited the massive leukemic cell infiltrations to sinusoidal spaces in spleen; (d) decrease the expression of Bcl-2, Raf-1, Erk-1 IFNgamma receptor and erythropoietin; (e) induce the expression of p53. Overall, our results suggest that berberine, curcumin and picroliv were able to suppress the progression of leukemia induced by FMuLv and further support their chemopreventive potential against virally induced cancers.

Topics: Animals; Antineoplastic Agents; Berberine; Biological Products; Cinnamates; Curcumin; Disease Progression; Friend murine leukemia virus; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glycosides; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Mice; Mice, Inbred BALB C; Uric Acid; Vanillic Acid