Effect of picroliv on antioxidant-system in liver of rats,after partial hepatectomy

Levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase in the serum of rats increased maximally at 12 h and bilirubin at 24 h, while total proteins decreased maximally at 48 h after partial hepatectomy. The levels of total lipids, reduced glutathione, glutathione peroxidase and glutathione reductase in liver increased maximally at 12 h and catalase at 24 h, but the activities of peroxidase, glutathione-S-transferase and superoxide dismutase decreased maximally at 12 h. After the period of maximal initial increase/decrease, the changes in these parameters in liver and serum started recovering towards their prehepatectomy levels. When a similar study was performed in rats fed 12 mg/kg body wt picroliv (an iridoid glycoside fraction of Picrorhiza kurroa) once daily for 7 days, the rate of recovery of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase in serum and total lipids, reduced glutathione, peroxidase, catalase and glutathione-S-transferase in liver was faster.     

Prevention of paracetamol-induced hepatic damage in rats by picroliv,the standardized active fraction from Picrorhiza kurroa

Single oral administration of paracetamol (2 g/kg body wt) to rats caused significant changes in the activities of γ-glutamyl transpeptidase, 5′-nucleotidase, succinate dehydrogenase, glucose-6-phosphatase and cytochrome P₄₅₀ and contents of glycogen and cholesterol in liver after 24 and 48 h. Total lipids and lipid peroxides in liver increased both at 24 and 48 h while protein content of liver decreased after 48 h. Levels of transaminases, alkaline phosphatase and bilirubin in serum also increased. The magnitude of these changes was more after 48 h of paracetamol administration. Picroliv, the iridoid glycoside fraction of Picrorhiza kurroa, when given orally to rats (6 and 12 mg/kg body wt for 7 days) caused significant reversal of the paracetamol-induced biochemical changes. The degree of protection at the two doses of picroliv was almost similar.     

Antioxidant and hepatoprotective activity of ethanol extract of Arachniodes exilis (Hance) Ching

Aim of the study

The study was aimed to investigate the ethanol extract of Arachniodes exilis for the antioxidant and hepatoprotective activity.

Materials and methods

Antioxidant activity was evaluated by different assays, including reducing power, lipid peroxidation, 2, 2′-diphenyl-1-picrylhydrazyl (DPPH), 2, 2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), superoxide anion, hydroxyl radicals and hydrogen peroxide. The hepatoprotective activity of ethanol extract was studied on mice liver damage induced by CCL₄ by monitoring biochemical parameters.

Results

The extract showed potent activities on reducing power, lipid peroxide, DPPH, ABTS, superoxide anion, hydroxyl radical and hydrogen peroxide. And oral administration of Arachniodes exilis at different doses resulted in significant improvement on the levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, malondialchehyche and superoxidedismutase.

Conclusion

The results indicate that this plant possesses potential antioxidant and hepatoprotective properties and has therapeutic potential for the treatment of liver diseases.     

Effect of Picroliv on Rifampicin-Induced Biochemical Changes in the Rat Liver and Serum

Rifampicin was administered to rats (50 mg/kg, i.p. daily) for 2, 6, 12 or 24 days and selected biochemical parameters in liver and serum were measured 24 h after the last injection. Concomitant administration of picroliv (12 mg/kg) showed maximum hepatoprotective activity in the 6 day schedule. Administration of picroliv during the recovery phase in 12 and 24 day schedule expedited recovery of most parameters.     

Hepatoprotective and toxicological assessment of an ethnomedicinal plant Euphorbia fusiformis Buch.-Ham.ex D.Don

Aim of the study

The tubers of Euphorbia fusiformis Buch.-Ham.ex D.Don (Euphorbiaceae) are traditionally used in India by the Malayali tribes of Chitteri hills, Eastern Ghats, Tamil Nadu to treat liver disorders. The objective of the present study was to assess the hepatoprotective potential and biosafety of Euphorbia fusiformis tuber upon administration thereby justifying the traditional claims.

Materials and methods

The hepatoprotective potential of the ethanol extract of Euphorbia fusiformis tuber against rifampicin induced hepatic damage was investigated in Wistar albino rats. The acute and subchronic toxicity were assessed in mice and rats, respectively.

Results

The ethanol extract of tubers (250 mg/kg p.o.) showed remarkable hepatoprotective effect against rifampicin induced hepatic damage in Wistar albino rats. The degree of protection was measured using the biochemical parameters serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), gamma glutamyl transpeptidase (GGTP), alkaline phosphatase (ALP), total bilirubin and total protein. Treatment with ethanolic extract prior to the administration of rifampicin significantly (P < 0.05 to P < 0.001) restored the elevated levels of the said parameters on a par with the control group. The single dose LD₅₀ was found to be 10,000 mg/kg bw when administered orally in mice. Subchronic toxicity studies in rats with oral doses of 125, 250 and 500 mg/kg exhibited no significant changes in body weight gain, general behavior, hematological and biochemical parameters. The histological profile of liver and kidney also indicated the non-toxic nature of this drug.

Conclusion

The ethanol extract of Euphorbia fusiformis tubers may have potential therapeutic value in the treatment of liver disorders and is safer to use even at higher doses when taken orally.     

Hepatoprotection of Graptopetalum paraguayense E. Walther on CCl₄-induced liver damage and inflammation

Aim of this study

Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. Therefore, we investigated the protective effects of Graptopetalum paraguayense E. Walther against carbon tetrachloride (CCl₄)-induced liver damage in rats.

Materials and methods

Water extracts of Graptopetalum paraguayense E. Walther (WGP) were administered for 8 consecutive weeks to male Sprague-Dawley rats. And a dose-dependent manner in preventing liver damage was confirmed. Moreover, the major ingredient of WGP, gallic acid, was also orally administrated in the CCl₄-induced rats. The hepatoprotective activity was assessed using various biochemical parameters such as antioxidant enzymes and histopathological studies.

Results

WGP ranging from 50 to 300 mg/kg bw administrations significantly lowered serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, and inhibited malondialdehyde (MDA) generation in CCl₄-treated rats. WGP increased cellular GSH level and antioxidant enzymes, including superoxide dismutase, glutathione reductase, and catalase. Serum tumor necrosis factor-alpha (TNF-α) was decreased in the group treated with CCl₄ plus WGP (150 and 300 mg/kg bw). Histopathological examination of livers showed that WGP reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl₄-treated rats. In contrary, 10 mg/kg bw of gallic acid was administrated, this dose was related with WGP (300 mg/kg bw), and had significantly decreased the AST and ALT compared to the CCl₄-treated group. Aforesaid results suggested that gallic acid from WGP offered antioxidative activity against CCl₄-induced oxidative liver damage.

Conclusions

Taken together, this study is the first time to suggest that Graptopetalum paraguayense E. Walther exerts hepatoprotection via promoting antioxidative and anti-inflammatory properties against CCl₄-induced oxidative liver damage.     

Trianthema portulacastrum affords antihepatotoxic activity against carbon tetrachloride-induced chronic liver damage in mice: reflection in subcellular levels

The efficacy of an ethanol extract of Trianthema portulacastrum as a hepatoprotective agent was investigated against carbon tetrachloride (CCl₄)-induced chronic liver injury in mice. The CCl₄ was administered per os (p.o.) three times a week for 5 weeks. Daily administration (p.o.) of T. portulacastrum plant extract at 100 or 150 mg/kg was started 2 weeks before the commencement of CCl₄ treatment and it continued during the entire period of the treatment. The extract dose-dependently decreased the activities of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, glutamate dehydrogenase and sorbitol dehydrogenase as well as serum levels of bilirubin and urea which were otherwise significantly elevated with the chronic CCl₄ regimen alone. There was a substantial increase in the activities of plasma membrane enzymes γ-glutamyl transpeptidase and 5′-nucleotidase and lysosomal enzymes acid phosphatase and acid ribonuclease in hepatic tissue following CCl₄ treatment. These changes were reversed towards normalization with the extract in a dose-dependent manner. The extract also restored CCl₄-induced inhibition of hepatic microsomal enzyme glucose-6-phosphatase. The activities of mitochondrial succinate dehydrogenase and adenosine 5′-triphosphatase which were significantly attenuated by CCl₄ administration remained unaltered following the extract therapy. Results of this study provide evidence that the extract possesses a marked liver protective action which is comparable to that of silymarin, a standard hepatoprotective drug. The probable mechanism by which this plant exerts cytoprotection has also been discussed. © 1997 John Wiley & Sons, Ltd.     

Stimulation of protein biosynthesis in rat hepatocytes by extracts of Momordica charantia

The in vivo effect of the administration of extracts of Momordica charantia on certain biochemical parameters of Sprague-Dawley rats was investigated. It was observed that there was an increase in muscle and liver protein levels, while there was a reduction in the levels of brain protein, muscle and liver glycogen. The activities of plasma L-alanine transaminase and alkaline phosphatase were reduced. The L-aspartate transaminase and adenosine triphosphatase activities were slightly elevated in whole plant extract treated rats while the L-aspartate transaminase was unaffected by the ethanol extract but reduced the adenosine triphosphatase activity.     

In vitro and in vivo hepatoprotective and antioxidant activity of ethanolic extract from Meconopsis integrifolia (Maxim.) Franch

Ethnopharmacological relevance

Meconopsis integrifolia (Maxim.) Franch is a high mountain endemic species used as a traditional Tibetan and Mongolian herb to treat hepatitis, pneumonia, and edema. This study aims to investigate the hepatoprotective and antioxidant effects of Meconopsis integrifolia ethanolic extract (MIE) in vitro and in vivo.

Materials and methods

The in vitro antioxidant property of MIE was investigated by employing various established systems. Rats with carbon tetrachloride (CCl₄)-induced liver injury were used to assess the hepatoprotective and antioxidant effect of MIE in vivo. The level or activity of alkaline phosphatase (ALP), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) in the blood serum and thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in the liver and kidney of the rats were assayed using standard procedures.

Results

MIE exhibited strong antioxidant ability in vitro. In the rats with CCl₄-induced liver injury, the groups treated with MIE and silymarin showed significantly lower levels of ALT, AST, ALP, and TB. MIE demonstrated good antioxidant activities in both the liver and kidney of the rats in vivo.

Conclusions

MIE exhibits excellent hepatoprotective effects and antioxidant activities in vitro and in vivo, supporting the traditional use of Meconopsis integrifolia in the treatment of hepatitis.     

Protection by Abana,a Herbomineral Preparation,against Myocardial Necrosis in Rats Induced by Isoproterenol

Abana, a herbomineral preparation, showed significant protection against the biochemical changes induced by isoproterenol in rats. In myocardial necrosis, the increased levels of serum creatine phosphokinase, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and γ-glutamyl transpeptidase were found to be reversed by Abana treatment. In addition the decreased levels of glycogen, γ-glutamyl transpeptidase, succinate dehydrogenase and mitochondrial oxygen uptake in heart were also significantly protected. This shows that Abana treatment could contribute to restoring myocardial integrity and cardiac function disturbed by isoproterenol-induced ischaemia.     

Hepatoprotective studies on Sida acuta Burm. f.

Ethnopharmacological relevance

Sida acuta Burm. f. (Malvaceae) is used in Indian traditional medicine to treat liver disorders and is useful in treating nervous and urinary diseases and also disorders of the blood and bile.

Aim of the study

Evaluation of the hepatoprotective properties of the methanolic extract of the root of Sida acuta (SA) and the phytochemical analysis of SA.

Materials and methods

The model of paracetamol-induced hepatotoxicity in Wistar rats, liver histopathological observations, hexobarbitone-induced narcosis and in vitro anti-lipid peroxidation studies were employed to assess the hepatoprotective efficacy of SA. Phytochemical assay of SA was conducted following standard protocols.

Results

Significant hepatoprotective effects were obtained against liver damage induced by paracetamol overdose as evident from decreased serum levels of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase and bilirubin in the SA treated groups (50, 100, 200 mg/kg) compared to the intoxicated controls. The hepatoprotective effect was further verified by histopathology of the liver. Pretreatment with Sida acuta extract significantly shortened the duration of hexobarbitone-induced narcosis in mice indicating its hepatoprotective potential. Phytochemical studies confirmed the presence of the phenolic compound, ferulic acid in the root of Sida acuta, which accounts for the significant hepatoprotective effects observed in the present study.

Conclusion

The present study thus provides a scientific rationale for the traditional use of this plant in the management of liver disorders.     

In Vivo Hepatoprotective Effect of Baicalein,Baicalin and Wogonin from Scutellaria rivularis

The in vivo hepatoprotective effect of baicalein, baicalin and wogonin, three major components isolated from Scutellaria rivularis Benth. were investigated in three experimental models. Liver damage was induced by acetaminophen (APAP), carbon tetrachloride (CCl₄) and β-D -galactosamine (D -GalN) in rats. Significant protective effects were seen by comparing the serum glutamate oxaloacetate transaminase (sGOT), serum glutamate pyruvate transaminase (sGPT) and histopathologic examination. All tested drugs, especially wogonin (5 mg/kg), markedly decreased the toxicity produced by D -GalN ( p <0.01). Wogonin (5, 10 mg/kg) also decreased APAP-induced hepatotoxicity. Baicalin (10 mg/kg) exhibited the best hepatoprotective effect on CCl₄-induced liver injuries, but had no significant effect on APAP-induced intoxication. In histopathologic observation, hepatic lesions caused by three hepatotoxins were markedly improved in drug-treated groups, compared with glycyrrhizin (GLZ) as a standard reference medicine.     

Antioxidative and hepatoprotective effect of CGX, an herbal medicine, against toxic acute injury in mice

Aim

CGX, a modified traditional Chinese herbal drug whose name means “liver cleaning,” is used to treat various liver disorders. This study investigated the protective effects of CGX and its mechanisms.

Material and methods

After pretreating ICR mice twice daily with CGX (po, 50 or 100 mg/kg) or distilled water for three consecutive days, acute liver injury was induced by a single injection of CCl₄ (ip, 10 mL/kg of 0.2% in olive oil) (n = 8 per group).

Results

Pretreatment with CGX significantly attenuated the elevation in biochemical parameters, such as alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) in serum, and the malondialdehyde concentrations in liver tissue. Pretreatment with CGX significantly restored the reduction of catalase activity and glutathione (GSH) content, but not superoxide dismutase (SOD) activity, and it inhibited the CCl₄-induced high expression of iNOS and TNF-α in hepatic tissue.

Conclusion

This study showed that CGX has hepatoprotective effects against free radical-induced acute injury via primarily antioxidative properties.     

Hepatoprotective effect of the fractions of Ban-zhi-lian on experimental liver injuries in rats

The hepatoprotective effect of various fractions (n-hexane, CHCl₃, EtOAc, n-BuOH, and H₂O) of Ban-zhi-lian derived from Scutellaria rivularis Benth. was studied against carbon tetrachloride (CCl₄), d-galactosamine (d-GalN) and acetaminophen (APAP)-induced acute hepatotoxicity in rats. Liver damage was assessed by quantifying serum activities of glutamate oxaloacetate transaminase (sGOT) and glutamate pyruvate transaminase (sGPT), as well as by histopathological examination. The results indicated that the CHCl₃ fraction and EtOAc fractions exhibited the greatest hepatoprotective effects on CCl₄-induced liver injuries, the CHCl₃ fraction and n-hexane fraction are most potent against d-GalN-induced intoxication, and the CHCl₃ fraction represented the most liver-protective effect on APAP-induced hepatotoxicity. The pathological changes of hepatic lesions caused by these three hepatotoxicants were improved by treatment with the fractions mentioned above, which were compared to Glycyrrhizin (GLZ) and Silymarin as standard reference medicines.     

Toxicological assessment of beta‐lapachone on organs from pregnant and non‐pregnant rats

Naphthoquinones have been studied extensively due to their activity as topoisomerase inhibitors. These enzymes are critical to DNA replication in cells. β‐Lapachone (beta‐lap) is an o‐naphthoquinone chemically obtained from lapachol. This work results in a toxicological evaluation of beta‐lap in Wistar rats observing the following parameters: teratology, histology, hematology and serum biochemistry. The data demonstrate teratogenic action at the doses used, as well as hematological alterations in the total leukocytes, monocytes and segmented. The biochemical data demonstrated an increase in gamma glutamyl transferase, alkaline phosphatase and glutamate pyruvate transaminase levels. Histological study showed significant alterations in the spleen, however, the liver and kidney did not present significant alterations. Copyright © 2009 John Wiley & Sons, Ltd.     

Hepatoprotective effect of leaf extracts of Andrographis lineata nees on liver damage caused by carbon tetrachloride in rats

The present study was conducted to evaluate the hepatoprotective effect of Andrographis lineata (Acanthaceae) extracts in carbon tetrachloride-induced liver injury in rats. Male Wistar rats with chronic liver damage, induced by subcutaneous injection of 50% v/v carbon tetrachloride in liquid paraffin at a dose of 3 mL/kg on alternate days for a period of 4 weeks, were treated with methanol and aqueous extracts of A. lineata orally at a dose of 845 mg/kg/day. The biochemical parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum bilirubin and alkaline phosphatase were estimated to assess the liver function. Histopathological studies of the liver were also carried out to confirm the biochemical changes. Histopathological examinations of liver tissue corroborated well with the biochemical changes. The activities of extracts were comparable to a standard drug. Hepatic steatosis, hydropic degeneration and necrosis were observed in the carbon tetrachloride treated group, while these were completely absent in the standard and extract treated groups. A. lineata extracts exhibited hepatoprotective action against carbon tetrachloride-induced liver injury. The present investigation established pharmacological evidence to support the folklore claim that it is used traditionally as a hepatoprotective agent.     

Hypolipedaemic activity of picroliv in albino rats

The hypolipidaemic action of picroliv, a standarized preparaton from Picrorhiza kurrooa, has been studied in normal as well as in triton- and cholesterol-fed rats. Serum lipids were found to be lowered by picroliv (25 mg/kg b.w.) in triton WR-1339-induced hyperlipaemia. Chronic feeding of this drug (6 mg/kg b.w.) in normal rats and in animals simultaneously treated with cholesterol (25 mg/kg b.w.) for 30 days caused lowering in the lipid and protein levels constituting β-lipoproteins followed by an increase in high density lipoprotein cholesterol in experimental animals. Picroliv alters lipolytic activities in plasma, liver, heart an adipose tissues and stimulated receptor mediated catabolism of low density lipoprotein. The lipid lowering action of the natural product is mediated through inhibition of cholesterol biosynthesis in liver, increased faecal bile acid excretion and enhanced plasma lecithin: cholesterol acyltransferase activity.     

Systems biochemical responses of rats to Kansui and vinegar-processed Kansui exposure by integrated metabonomics

Ethnopharmacological relevance

The dried root of Kansui (Euphorbia kansui L.) is an effective and commonly used traditional Chinese medicine. Even so, Kansui cannot be satisfactorily applied clinically because of toxic side effects. In China, the most common Kansui-processing method uses vinegar to reduce its toxicity. The present study was designed to investigate the toxic effects caused by Kansui and evaluate detoxification of Kansui by vinegar processing of Kansui.

Materials and method

Thirty male Sprague Dawley (SD) rats were randomly assigned to five groups of six rats. Two experimental groups were oral gavaged with 7.875 and 15.75 g Kansui/kg body weight, two treated with 7.875 and 15.75 g VP-Kansui/kg body weight for 14 d, and the control group concurrently subjected to oral gavage with only distilled water. On day 14, plasma, liver and kidney tissues were collected from all rats for biochemistry assessments, histopathological examination, and NMR analyses.

Results

The metabonome of rats treated with Kansui and vinegar-processed (VP-) Kansui was found to differ from that of controls. In liver extracts, the variational metabolites included elevated concentrations of isoleucine, leucine, valine, glutamate, and phenylalanine, with decreased taurine, glucose, and glycogen. However, changes in lysine, methionine, choline, phosphorylcholine, and tyrosine were only observed in Kansui-treated rats. In kidney extracts, prominent changes included elevations in isoleucine, leucine, valine, methionine, creatine/creatinine, and phenylalanine as well as decreased glutamine. Only Kansui treatment induced variations in alanine, lysine, acetate, choline, and phosphorylcholine.

Conclusion

Perturbations in endogenous metabolites induced by Kansui correlated with disturbances in glycolysis and amino acid and lipid metabolism, while biochemical pathway disorders caused by VP-Kansui only involved glycolysis and amino acid metabolism. All results were confirmed by histopathological examination of liver and kidney tissues and clinical biochemistry analyses.     

Hepatoprotective effects of Taiwan folk medicine: Alternanthera sessilis on liver damage induced by various hepatotoxins

The hepatoprotective effects of the Taiwanese herb ‘Horngtyan-wu’ (Alternanthera sessilis (L.) DC.) were investigated in three kinds of experimental animal model. Acute hepatitis was induced by various chemicals such as carbon tetrachloride (31.25 μL/kg, i.p.) or acetaminophen (paracetamol; 600 mg/kg, i.p.) in mice and D(+)-galactosamine (188 mg/kg, i.p.) in rats. When treated with A. sessilis (300 mg/kg, p.o.) at 2, 6 and 10 h, a reduction in elevation of serum glutamate oxaloacetic transaminase (SGOT) and glutamate pyruvic transaminase (SGPT) levels could be observed at 24 h after administration of the three hepatotoxins. These serological observations were also confirmed by histopathological examinations including centrilobular necrosis, eosinophilic bodies, pyknotic nuclei, microvesicular degeneration of hepatocytes and others. The liver microscopic examination showed a noted improvement in groups receiving A. sessilis. All pharmacological and histopathological effects were compared with observations using the hepatoprotective Chinese herb, Bupleurum chinense (Family Umbelliferae). It was confirmed that A. sessilis has hepatoprotective effects against liver injuries induced by hepatotoxins with different mechanisms.     

Protective and Therapeutic Effect of the Indonesian Medicinal Herb Curcuma xanthorrhiza on β-D-Galactosamine-induced Liver Damage

The present study was carried out to investigate the hepatoprotective effects of a dose of C. xanthorrhiza on acute hepatotoxicity induced in rats by a single dose of β-D -galactosamine (288 mg/kg, i.p.), and its mechanism of action. C. xanthorrhiza (100 mg/kg) was administered p.o. to experimental animals according to the protocol followed by the i.p. administration of a single dose of hepatotoxin. Hepatoprotective activity was monitored by estimating serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) levels and histopathological changes in the livers of C. xanthorrhiza -treated and untreated groups of animals. The results clearly indicated that the extract of C. xanthorrhiza significantly reduced the acute elevation of serum transaminases induced by hepatotoxin, and alleviated the degree of liver damage at 24 h after the intraperitoneal administration of the hepatotoxins.