ABSTRACT
ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.
ABSTRACT
ObjectiveTo explore the pharmacodynamic effect of the water extract of Citri Grandis exocarpium （WEC） on mice with alcohol-induced acute liver injury and provide data support for the development of this medicinal for anti-alcoholism and liver protection. MethodThe main components of WEC were determined by high performance liquid chromatography （HPLC）. Sixty Balb/c mice were randomized into 6 groups： control group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， model group （equal volume of 0.5% carboxymethyl cellulose sodium solution）， low-， medium-， and high-dose WEC groups （0.5， 1.0， 2.0 g·kg-1）， and Haiwang Jinzun tablet positive control group （2.0 g·kg-1）. The administration lasted 14 days. One day before the end of the administration， mice were fasted for 12 h with free access to water. The mice， except the control group， were given 56° Chinese liquor （13 mL·kg-1）. After 2 h， blood was taken from eyeballs and the liver was dissected and weighed. Automatic biochemical analyzer was employed to detect the expression of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and alcohol dehydrogenase （ADH）. The pathological changes of liver tissues were observed based on hematoxylin-eosin （HE） staining， and apoptosis of hepatocytes based on TUNEL/DAB staining. The expression of proteins related to apoptosis was detected by Western blot. ResultAccording to the HPLC fingerprint， the main components of WEC were rhoifolin and naringin. Compared with the control group， the model group showed increase in liver/body weight ratio （P<0.01） and the expression of ALT and AST （P<0.05， P<0.01）， decrease in the expression of ADH （P<0.05）， blurred structure of hepatic lobules， pathological changes of liver tissue， loose cytoplasm with edema， severe steatosis， rise of the TUNEL-positive rate （P<0.01）， reduction in expression of Bcl-2 （P<0.01）， and increase in Bax and Caspase-3 （P<0.01）. Compared with the model group， medium-dose WEC lowered liver/body weight ratio （P<0.05）. All doses of WEC depressed the activity of ALT and AST （P<0.05， P<0.01）， up-regulated the expression of ADH （P<0.05）， significantly improved the pathological features of alcohol-induced cytoplasmic porosity， edema， and steatosis， down-regulated the TUNEL-positive rate （P<0.05， P<0.01）， enhanced the expression of Bcl-2 （P<0.05）， and decreased Bax and Caspase-3 （P<0.01）. ConclusionWEC regulates the expression of ALT， AST， and ADH and improves hepatic steatosis and hepatocyte apoptosis to fight against acute liver injury.
ABSTRACT
Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.
Subject(s)
Animals , Humans , Male , Rats , Amino Acids , Metabolism , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Metabolism , Drugs, Chinese Herbal , Gas Chromatography-Mass Spectrometry , Liver , Metabolism , Metabolomics , Phyllanthus , Chemistry , Rats, Sprague-Dawley , Taurocholic Acid , MetabolismABSTRACT
O chá-verde (Camellia sinensis (L.) Kuntze) é utilizado por suas propriedades: antioxidante, quimioprotetora e antiinflamatória em varias situações patológicas, principalmente frente a compostos químicos cancerígenos. Para tanto se avaliou o efeito hepatoprotetor do extrato de chá verde (ECV) sobre a lipoperoxidação e necrose provocada pelo agente cancerígeno Dietilnitrosamina (DEN) no fígado de ratos machos Wistar. Os ratos foram expostos a dose única de 200 mg/kg de DEN via intra peritoneal e tratados por via oral de 120 mg/kg de ECV em diferentes momentos experimentais. Após 24 h em relação a exposição ao DEN, os animais foram sacrificados sendo avaliado: os níveis de AST/ALT no plasma, a lipoperoxidação por quantificação de TBARS e FOX no fígado e a ocorrência de necrose e hemorragia hepática através do estudo histopatológico. A ação quimioprotetora e a diminuição da lipoperoxidação foram verificadas pela diminuição das transaminases, TBARS, FOX e redução da necrose hepática. A avaliação confirmou a importância de se utiliza o chá verde como agente quimioprotetor, principalmente na forma preventiva.
Green tea (Camellia sinensis (L.) Kuntze) is used for its properties: antioxidant, chemoprotector and anti-inflammatory in several pathological situations, mainly those facing carcinogen chemical substances. This work has evaluated the hepatic protection effect of the green tea extract (GTE) on lipoperoxidation and necrosis, induced by the carcinogenic DEN in rats´ liver. Adult male Wistar rats were used and exposed to one only intra peritoneal dose of 200 mg/kg of DEN, and orally 120 mg/kg of ECV in different experimental moments. After 24 h of a DEN treatment, the animals were sacrificed and the following aspects were evaluated: the AST/ALT levels in plasma, lipoperoxidation of TBARS and FOX in the liver. Necrosis and Hepatic hemorrhage were observed through a histological examination. The chemoprotector action and the decrease in lipoperoxidation were detected after a decrease of AST/ALT, TBARS, FOX and hepatic necrosis. The evaluation of these results confirmed the importance of the use of the green tea as a chemoprotector agent, particularly as a preventive method.
ABSTRACT
Objective: To study the protective function of Gardenia yellow (GY) against CCl 4 induced hepatotoxicity in mice.Methods: Healthy Kunming male mice, weighting (20?2) g, 10 per group were randomized into 5 groups:control group, CCl 4 injured group, low dose group(CCl 4 injured+0.1 ml GY solution), medium dose group(CCl 4 injured+ 0.2 ml GY solution) and high dose group(CCl 4 injured+0.4ml GY solution). GY solution was given i.g. 5 d prior to CCl 4 injury. Serum glutamate pyruvate transaminase(SGPT) and glutamic oxaloacetic transaminase(SGOT) and lactic dehydrogenase(LDH) activities were determined 18 h after CCl 4 injury. Hepatic malondialdehyde(MDA), glutathione(GSH) and liver index were also detected. Results: In GY treated groups, the increases of serum SGOT, SGPT, LDH activities and liver GSH were inhibited obviously. The elevations of MDA and liver index were prevented significantly. The lesions in liver lobule were ameliorated obviously. Conclusion: Gardenia yellow can protect against CCl 4 induced hepatotoxicity.