Zederone, a Sesquiterpene From Curcuma elata Roxb, Is Hepatotoxic in Mice (original) (raw)
Related papers
Pharmaceutical Biology, 2015
Context: Curcuma comosa Roxb. (Zingiberaceae) has traditionally been used as an anti-inflammatory agent in liver, and recent study has shown its hepatoprotective effect against CCl 4-induced liver injury in vivo. Objective: This study further assesses the protective effect of C. comosa extracts and its isolated compounds against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in isolated primary rat hepatocytes. Materials and methods: Isolated primary hepatocytes were pretreated with either ethanol (5-50 mg/ml) or hexane extract (1-50 mg/ml), or two diarylheptanoids (4-35 mM): compound D-91 [1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol] and compound D-92 [(3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol], from C. comosa for 2 h prior to exposure to 1.5 mM t-BHP for 15 and 30 min. Their hepatoprotective activities were then determined. Results: t-BHP markedly caused the formation of MDA and ALT leakage from the hepatocytes. Pretreatment with the C. comosa ethanol extract showed greater protective effect than the hexane extract, and the effect was concentration related. Treating the hepatocytes with compound D-92 provided greater protective effect than compound D-91. IC 50 values of compounds D-91, D-92, and silymarin for the protection of ALT leakage at 30 min were 32.7 ± 1.1, 9.8 ± 0.7, and 160 ± 8 mM, respectively. Further investigation showed that compound D-92 was more effective in maintaining the intracellular glutathione content in the t-BHP treated group, whereas the reduction in antioxidant enzymes, glutathione peroxidase and glutathione-S-transferase activities, were not improved. Discussion and conclusion: Results suggest that diarylheptanoids are the active principles that provide protection against t-BHP-induced injury. Their ability to maintain intracellular glutathione content is the main mechanisms underlying the protective action.
Journal of Ethnopharmacology, 2010
Aim of the study: To investigate the protective effect and possible mechanism of Curcuma comosa hexane extract on CCl 4 -induced liver injury in adult male mice. Materials and methods: Hepatotoxicity was induced by an intraperitoneal injection of CCl 4 and was evaluated after 24 h from the elevations of plasma alanine transaminase (ALT) and aspartate transaminase (AST) activities, and histological analysis of liver injuries. Hexane extract of Curcuma comosa was given at different time points from 1 to 72 h, prior to CCl 4 administration and the protection from liver injury was assessed. Results: CCl 4 -induced damage to liver cells was resulted in elevations of plasma ALT and AST activities. Pretreatment with Curcuma comosa hexane extract 24 h at a dose of 100, 250, and 500 mg/kg BW resulted in a dose-dependent prevention of the increases in plasma ALT and AST activities as well as time dependent. The protective effect of the extract at a dose of 500 mg/kg BW was seen at 12-24 h. Pretreatment of the extract completely prevented elevation of plasma ALT and AST activities, and centrilobular necrosis. The protective effect of Curcuma comosa was associated with restoration of hepatic glutathione content, and CYP2E1 catalytic activity, and its mRNA and protein levels as well as increase in activity of glutathione-S-transferase (GST). Conclusion: Curcuma comosa has a potent protective property against CCl 4 -induced hepatic injuries via the activation of detoxifying mechanisms (GST) as well as reduction of the bioactive toxic metabolites. Therefore, Curcuma comosa may be beneficial for prevention of hepatotoxicity.
Bioorg Medicinal Chem Letter, 1998
Hepatoprotective sesquiterpenes were isolated from the aqueous acetone extract of Zedoariae Rhizoma, the rhizome of Curcuma zedoaria ROSCOE (Zingiberaceae). Principal sesquiterpenes, furanodiene, germacrone, curdione, neocurdione, curcumenol, isocurcumenol, aerugidiol, zedoarondiol, and curcumenone and curcumin were found to show potent protective effect on D-galactosamine (D-GaIN) / lipopolysaccharide (LPS)-induced acute liver injury in mice. Plausible action mechanisms for their hepatoprotective activity were clarified on the basis of the inhibitory effect on D-GaiN-induced cytotoxicity in primary cultured rat hepatocytes, LPS-induced NO production in cultured mouse peritoneal macrophages, and D-GaIN / tumor necrosis factor-c~
Bioorganic & Medicinal Chemistry Letters, 1998
Hepatoprotective sesquiterpenes were isolated from the aqueous acetone extract of Zedoariae Rhizoma, the rhizome of Curcuma zedoaria ROSCOE (Zingiberaceae). Principal sesquiterpenes, furanodiene, germacrone, curdione, neocurdione, curcumenol, isocurcumenol, aerugidiol, zedoarondiol, and curcumenone and curcumin were found to show potent protective effect on D-galactosamine (D-GaIN) / lipopolysaccharide (LPS)-induced acute liver injury in mice. Plausible action mechanisms for their hepatoprotective activity were clarified on the basis of the inhibitory effect on D-GaiN-induced cytotoxicity in primary cultured rat hepatocytes, LPS-induced NO production in cultured mouse peritoneal macrophages, and D-GaIN / tumor necrosis factor-c~
Hepatic hyperplasia and damages induces by zearalenone Fusarium mycotoxins in BALB/c mice
Arquivos de Gastroenterologia, 2012
CONTEXT: Zearalenone is a mycoestrogen and considered a mycotoxin. OBJECTIVE: To establish whether zearalenone produced hepatotoxicity via oral administration. METHODS: Zearalenone was orally administered at a dose of 50 mg, 100 mg and 200 mg ZEN/body weight/daily, respectively, for 14 days to three groups of BALB/c mice. Diagnostic modalities used to evaluate hepatic damage and impaired hepatic function pre- and post zearalenone administration included hepatic marker enzyme activity, pentobarbital sleeping time, cytochrome P-450 activities and histopathologic evaluation of liver. RESULTS: Significant histopathologic changes viz. sinusoidal congestion, cytoplasmic vacuolization, hepatocellular necrosis and neutrophil infiltration were observed after evaluating of liver section from each group after accumulated zearalenone exposure. Further, zearalenone exposure increased activities of alanine transaminase, aspartate transaminase and lipid peroxides whereas activities of tissue gluta...
2013
Background: Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats. Methods: The hepatoprotective effect of CLRE was measured in a rat model of thioacetamide-induced liver cirrhosis over 8 weeks. Hepatic cytochrome P450 2E1 and serum levels of TGF-β1 and TNF-α were evaluated. Oxidative stress was measured by malondialdehyde, urinary 8-hydroxyguanosine and nitrotyrosine levels. The protective activity of CLRE free-radical scavenging mechanisms were evaluated through antioxidant enzymes. Protein expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in animal blood sera was studied and confirmed by immunohistochemistry of Bax, Bcl2 proteins and proliferating cell nuclear antigen.
Effects of Curcuma Comosa Extracts on Hepatic Cytochrome P450 Activities in Rats
2010
Curcuma comosa Roxb. (Zingiberaceae) is an indigenous plant of Thailand. The rhizome of this plant has been widely used in Thai traditional medicine for treatment of abnormal uterine symptoms. The purpose of this study was to investigate effects of C. comosa hexane extract and ethanolic extract on hepatic cytochrome P450 (CYP) in rats. Fifty male Wistar rats were randomly divided into 5 groups (10 rats/group). Rats were given orally with C. comosa hexane extract or ethanolic extract (250 and 500 mg/kg/day) or corn oil in a control group for 30 consecutive days. At the end of the treatment, rats were sacrificed and liver microsomes were prepared. Hepatic microsomal total CYP content and CYP activity were determined. The results showed that both C. comosa hexane and ethanolic extracts at 250 mg/kg/day caused a significant increase of total CYP contents and the activity of CYP1A1. Lower dose of both extracts (250 mg/kg/day) caused a more increase of CYP1A1 activity than the higher dose (500 mg/kg/day). Also, both C. comosa hexane and ethanolic extracts caused a dose-dependent increase of CYP2B1/2B2 activities and the increase was higher in the hexane extract group than the ethanolic extract group. Hexane and ethanolic extracts of C. comosa did not affect CYP1A2, CYP2E1 and CYP3A activities. These results indicated the possibilities of C. comosa hexane and ethanolic extracts regarding herb-drug interactions and the increase risk of toxicity, mutagenesis and/or carcinogenesis from drugs or compounds that are metabolized or bioactivated via CYP1A1 and CYP2B1/2B2
International Journal of Research in Pharmaceutical Sciences, 2020
The modern medicine gets up a massive hike in the treatment of various ailments but scarcely any drugs having to stimulate liver activity, offering tutelage to the liver from any harm or promote the palingenesis of hepatic cells. However, a variety of herbal drugs applied in the conventional system of medicine for liver efficiency. Therefore, rhizome of Curcuma amada (Family: Zingiberaceae) are selected to allocate the hepatoprotective activity in scientifically approbate experimental models. This study is an effort to explore the 50% ethanolic extract of rhizome of Curcuma amada (CAE) in a different experimental model for hepatoprotective activities and in vitro antioxidant. 50% ethanolic extract of Curcuma amada (CAE) (100 and 200mg/kg) hepatoprotective efficiency was examined against paracetamol (1000 mg/kg) induced hepatotoxicity, elevated hepatic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), total bilirubin direct bili...
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, 2010
This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl 4)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100 mg/kg of CLE or 100 mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl 4 administration. In addition, the CLE control group was pretreated with 100 mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl 4 (20 mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the CCl 4-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the CCl 4-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the CCl 4-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against CCl 4-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.
2021
DOI: 10.33086/ijmlst.v3i1.1927 Abstract High doses of paracetamol create necrosis in the liver and produce free radicals. When liver function decreased in a long time, it will lead to severe liver damage and it will be irreversible. Rhizome of Curcuma zedoaria has the potential effect as an antioxidant. It is assumed that its properties inhibit the formation of free radicals which formed from toxic doses of paracetamol. The aim of this study was to examine the histological structure of the liver and to determine malondialdehyde (MDA) levels in the administration of C. zedoaria toxic dose and paracetamol on the rats (Rattus norvegicus). The study was used twenty-four rats divided into four groups (positive control: carboxy methyl cellular (CMC) 0.5%; negative control: paracetamol 1.35g/kg body weight; treatment group 1 (T1): C. zedoaria 105mg/200g and paracetamol 1.35g/kg Body weight 2 hours later, and treatment group 2 (T2): paracetamol 1.35g/ kg body weight and C. zedoaria 105 mg/2...