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.     

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.     

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.     

Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage

The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.     

Protective effect of leaf extract of Ficus hispida Linn. against paracetamol-induced hepatotoxicity in rats

The methanol extract of the leaves of Ficus hispida Linn. (Moraceae) was evaluated for hepatoprotective activity in rats by inducing acute liver damage by paracetamol (750 mg/kg, p.o.). The extract at an oral dose of 400 mg/kg exhibited a significant protective effect by lowering the serum levels of transaminase (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). These biochemical observations were supplemented by histopathological examination of liver sections. The activity of extract was also comparable to that of Liv-52 a known hepatoprotective formulation.     

Hepatoprotective activity of Centaurium erythraea on acetaminophen-induced hepatotoxicity in rats

The methanol extract of the leaves of Centaurium erythraea L. (Gentianaceae) was evaluated for hepatoprotective activity against acetaminophen-induced liver toxicity in rats. An oral dose of 300 mg/kg/day for 6 days or a single dose of 900 mg/kg for 1 day exhibited a significant protective effect by lowering serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH). The activity of the extract was supported by histopathological examination of liver sections.     

Preventive effect of the Taiwan folk medicine Ixeris laevigata var. oldhami on α‐naphthyl‐isothiocyanate and carbon tetrachloride‐induced acute liver injury in rats

The hepatoprotective effects of Ixeris laevigata Sch‐Bip. var. oldhami Kitam. (IL) were studied on cholestatic hepatitis induced by α‐naphthylisothiocyanate (ANIT, 100 mg/10 mL/kg, in olive oil, i.p.) and acute hepatitis induced by carbon tetrachloride (20% CCl₄/olive oil, 1.5 mL/kg, i.p.) in rats. Hepatoprotective activity was monitored by estimating the serum transaminases levels and the histopathological changes in the livers of experimental rats. The pretreatment of animals with IL, extract (0.3–2.0 g/kg orally) significantly inhibited the acute elevation of serum transaminases, as well as the hepatotoxin‐induced histopathological changes in the livers of the experimental rats. Copyright © 2002 John Wiley & Sons, Ltd.     

Studies on hepatoprotective and antioxidant actions of Strychnos potatorum Linn. seeds on CCl4-induced acute hepatic injury in experimental rats

Strychnos potatorum Linn. seeds are used in the Indian traditional system of medicine for the treatment of hepatopathy, nephropathy, gonorrhoea, leucorrhoea, gastropathy, bronchitis, chronic diarrhoea, strangury, renal and vesicle calculi, diabetes and eye diseases. The present study describes the hepatoprotective and antioxidant activities of the seed powder (SPP) and aqueous extract (SPE) of Strychnos potatorum seeds against CCl4-induced acute hepatic injury. Hepatic injury was achieved by injecting 3 ml/kg, s.c. of CCl4 in equal proportion with olive oil. Both SPP and SPE at the doses 100 and 200 mg/kg, p.o. offered significant (p < 0.001) hepatoprotective action by reducing the serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT). They also reduced the elevated levels of ALP and serum bilirubin. Reduced enzymic and nonenzymic antioxidant levels and elevated lipid peroxide levels were restored to normal by administration of SPP and SPE. Histopathological studies further confirmed the hepatoprotective activity of SPP and SPE when compared with the CCl4 treated control groups. The results obtained were compared with Silymarin (50 mg/kg, p.o.), the standard drug. In conclusion, SPE (200 mg/kg, p.o.) showed significant hepatoprotective activity similar to that of the standard drug, Silymarin (50 mg/kg, p.o.).     

Hepatoprotective effect of extracts from Pergularia daemia Forsk

Pergularia daemia (Asclepiadaceae) is a perennial herb growing widely along the road sides of India. It has been used in folk medicine for the treatment of liver disorders. The aim of this work is to study the hepatoprotective effect of crude ethanolic and aqueous extracts from the aerial parts of Pergularia daemia. The aqueous and ethanolic extracts obtained from aerial parts of Pergularia daemia were evaluated for hepatoprotective activity in rats by inducing liver damage by carbon tetrachloride. The ethanolic extract at an oral dose of 200 mg/kg exhibited a significant (P<0.05) protective effect by lowering serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin and total cholesterol and increasing the levels of total protein and albumin levels as compared to silymarin used as a positive control. These biochemical observations were supplemented by histopathological examination of liver sections. The activity may be a result of the presence of flavonoid compounds. Furthermore, the acute toxicity of the extracts showed no signs of toxicity up to a dose level of 2000 mg/kg. Thus it could be concluded that ethanolic extract of Pergularia daemia possesses significant hepatoprotective properties.     

Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats

Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl₄)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl₄-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl₄ was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl₄-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients.     

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.     

Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats

Seeds of Apium graveolens L. (Apiaceae) and Hygrophila auriculata (K. Schum.) Heine (Syn. Astercantha auriculata Nees, Acanthaceae) are used in Indian systems of medicine for the treatment of liver ailments. The antihepatotoxic effect of methanolic extracts of the seeds of these two plants was studied on rat liver damage induced by a single dose of paracetamol (3 g/kg p.o.) or thioacetamide (100 mg/kg, s.c.) by monitoring several liver function tests, viz. serum transaminases (SGOT and SGPT), alkaline phosphatase, sorbitol dehydrogenase, glutamate dehydrogenase and bilirubin in serum. Furthermore, hepatic tissues were processed for assay of triglycerides and histopathological alterations simultaneously. A significant hepatoprotective activity of the methanolic extract of the seeds of both the plants was reported.     

Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn

The hepatoprotective effects of rubiadin, a major constituent isolated from Rubia cordifolia Linn., were evaluated against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Rubiadin at a dose of 50, 100 and 200 mg/kg was administered orally once daily for 14 days. The substantially elevated serum enzymatic activities of serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and gamma-glutamyltransferase (gamma-GT) due to carbon tetrachloride treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were also restored towards normalization. In addition, rubiadin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4 intoxicated rats in a dose dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post treatment against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that rubiadin has a potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats.     

Protective effect of alpha- and beta-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice

In the search of hepatoprotective agents from natural sources, alpha- and beta-amyrin, a triterpene mixture isolated from the trunk wood resin of folk medicinal plant, Protium heptaphyllum was tested against acetaminophen-induced liver injury in mice. Liver injury was analysed by quantifying the serum enzyme activities and by histopathological observations. In mice, acetaminophen (500 mg/kg, p.o.) caused fulminant liver damage characterized by centrilobular necrosis with inflammatory cell infiltration, an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, a decrease in hepatic glutathione (GSH) and 50% mortality. Pretreatment with alpha- and beta-amyrin (50 and 100 mg/kg, i.p. at 48, 24, and 2 h before acetaminophen) attenuated the acetaminophen-induced acute increase in serum ALT and AST activities, replenished the depleted hepatic GSH, and considerably reduced the histopathological alterations in a manner similar to N-acetylcysteine, a sulfhydryls donor. Also, the acetaminophen-associated mortality was completely suppressed by terpenoid pretreatment. Further, alpha- and beta-amyrin could potentiate the pentobarbital (50 mg/kg, i.p.) sleeping time, suggesting the possible suppression of liver cytochrome-P450. These findings indicate the hepatoprotective potential of alpha- and beta-amyrin against toxic liver injury and suggest that the diminution in oxidative stress and toxic metabolite formation as likely mechanisms involved in its hepatoprotection. In conclusion, this study supports the traditional use of Protium heptaphyllum resin as a medicinal agent and suggests the feasibility of developing herbal drugs for treatment of liver disorders.     

Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves

In present study, the hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves were evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. The extracts at dose of 200mg/kg were administered orally once daily. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (SALP) and total bilirubin were restored towards normalization significantly by the extracts. Silymarin was used as standard reference and exhibited significant hepatoprotective activity against carbon tetrachloride induced haptotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that Momordica dioica Roxb. leaves have potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats. Ethanolic extract was found more potent hepatoprotective. Meanwhile, in vivo antioxidant and free radical scavenging activities were also screened which were positive for both ethanolic and aqueous extracts. This study suggests that possible mechanism of this activity may be due to free radical-scavenging and antioxidant activities which may be due to the presence of flavonoids in the extracts.     

Mikania cordata root extract in the inhibition of lipid peroxidation and reduction of enzyme leakage in mice with carbon tetrachloride induced liver damage

The effects of Mikania cordata root extract on carbon tetrachloride (CCl₄) induced liver injury were investigated. Lipid peroxidation, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and serum lactate dehydrogenase (LDH) were used as the marker for functional efficiency of the liver cells. A 7.8% inhibition of lipid peroxide levels in liver homogenate was noted at a dose of 10 mg/kg and the inhibition was more prominent (68.7%) at the optimum dose level of 150 mg/kg. The inhibitory values were 4.3% and 30.4% at the low and the high (optimum) doses tested, respectively, in the case of lipid peroxide levels in the hepatic lipid fraction. At a dose of 150 mg/kg, a maximum inhibition of the increased enzyme levels was observed (i.e. SGOT, 15.6%; SGPT, 13.4%; LDH, 22.8%). This observation suggests that Mikania cordata root extract induced a recovery from the damage caused in liver tissue during CCl₄ administration.     

Anti-inflammatory and hepatoprotective activity of peh-hue-juwa-chi-cao in male rats

Peh-hue-juwa-chi-cao (PHJCC) is a common commercial name for the herbal extract of either Hedyotis diffusa (HD), H. corymbosa (HC), or Mollugo pentaphylla (MP). The present study was carried out to investigate the anti-inflammatory and hepatoprotective effects of these three extracts in rats. The results indicated that extracts of HC, HD and MP possess anti-inflammatory activity, and that MP has the greatest inhibition against carrageenan-induced paw edema. In the hepatoprotective study, results indicated that the three plant extracts significantly reduced the acute elevation of serum glutamate oxalate transaminase (sGOT) and serum glutamate pyruvate transaminase (sGPT) concentration, and alleviated the degree of liver damage 24 hours after the intraperitoneal administration of hepatotoxins.     

Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract

Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.     

The hepatoprotective effects of Limonium sinense against carbon tetrachloride and beta-D-galactosamine intoxication in rats

In the present study, the hepatoprotective action of Limonium sinense (Plumbaginaceae) was evident after carbon tetrachloride (CCl(4)) and beta-D-galactosamine (D-GalN), respectively, challenge in rats. The plant materials were divided into two parts: (1) the roots extracted with water (WRE) and (2) the leaves extracted with methanol and fractionated with chloroform (CLE). Both WRE and CLE were extremely flavonoid-enriched extracts. In an CCl(4)-induced acute liver damage study, pretreatment with WRE at 300 mg/kg i.p. and CLE at 100 mg/kg i.p. significantly reduced the amino-transaminases levels of SGOT (p < 0.01) and SGPT (p < 0.01) previously increased by CCl(4) intoxication. In D-GalN-induced acute liver damage study, administration of WRE (300 and 500 mg/kg) or CLE (100 mg/kg) p.o. also significantly reduced the SGOT (p < 0.01) and SGPT (p < 0.01) levels previously increased by D-GalN intoxication. Furthermore, the serum triglyceride level was increased after pretreatment with WRE or CLE previously reduced by D-GalN intoxication. All of the liver function profiles were confirmed to have improvement of liver lesion in histopathological observation. In an acute toxicity test on ICR mice, the LD(50) of WRE was 777.6 mg/kg i.p. An in vitro study showed that CLE possessed a more potent cytotoxicity to human hepatocellular carcinoma cells (Hep3B) (EC(50) = 43.1 micro g/mL) than the other organic fractions, which were fractionated from methanol extracts of the leaves of L. sinense. The present results conclude that L. sinense possesses a hepatoprotective efficacy, and is relatively safe in rats.