Hepatoprotective properties of Caesalpinia sappan Linn. heartwood on carbon tetrachloride induced toxicity

Aim of the study was to investigate the methanol and aqueous extracts of heartwood of C. sappan for its hepatoprotective activity against CCl4 induced toxicity in freshly isolated rat hepatocytes and animals. Freshly isolated rat hepatocytes were exposed to CCl4 (1%) along with/without various concentrations of methanolic and aqueous extract of C. sappan (1000-800 microg/ml) and the levels of selected liver enzymes were estimated. Antihepatotoxic effect of methanolic extract was observed in freshly isolated rat hepatocytes at concentrations 1000-800 microg/ml and was found to be similar to that of standard drug silymarin. Wistar strain albino rat model was used for the investigation of in vivo hepatoprotective properties of aqueous and methanolic extract of C. sappan (100 and 200 mg/kg body weight). Liver damage was induced by ip administration of CCl4 (30%) suspended in olive oil (1 ml/kg body weight). Both the tested extracts showed potent hepatoprotective activity at 200 mg/kg body weight test dose which was comparable with that of the standard silymarin used in similar test dose. The methanolic and aqueous extract was able to restore the biochemical levels to normal which were altered due to CCl4 intoxication in freshly isolated rat hepatocytes and also in animals.     

Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats.

Effect of A. indica leaf extract on serum enzyme levels (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, acid phosphatase and alkaline phosphatase) elevated by paracetamol in rats was studied with a view to observe any possible hepatoprotective effect of this plant. It was interesting to observe that serum enzyme levels were much elevated in paracetamol induced animals than in those receiving a combination of paracetamol and lead extract. It is stipulated that the extract treated group was protected from hepatic cell damage caused by paracetamol induction. The findings were further confirmed by histopathological study of liver.     

Hepatoprotective action of ethanolic extracts of Melia azedarach Linn. and Piper longum Linn and their combination on CCl4 induced hepatotoxicity in rats

A comparison of analysis in evaluating the hepatoprotective action of ethanolic extract of M. azedarach (MAE) and P. longum (PLE) with their combination biherbal extract (BHE) against carbon tetrachloride (CCl4) induced hepatic damage is reported in albino rats. There was a marked elevation of serum marker enzyme levels in CCl4 treated rats, which were restored towards normalization in the drug (MAE and/or PLE:50 mg/kg body weight po, once daily for 14 days) treated animals. The biochemical parameters like total protein, total bilirubin, total cholesterol, triglycerides, and urea were also restored towards normal levels. The combined BHE showed more significant reduction of the enzymes than MAE or PLE against CCl4 induced hepatotoxicity. The results strongly indicate that BHE has more potent hepatoprotective action than MAE or PLE individually against CCl4 induced hepatic damage in rats. Among these extracts, BHE showed similar hepatoprotective action to silymarin, which was the positive control in this study.     

Antioxidant and hepatoprotective effect of the ethyl acetate extract of Enicostemma axillare (Lam). Raynal against CCL4-induced liver injury in rats

Enicostemma axillare is used in Indian traditional medicine as a liver tonic. Its ethyl acetate extract has shown potent in vitro antioxidant activity and found to contain 7.26% of a bitter secoiridoid glycoside, swertiamarin. Hence, in the present study the ethyl acetate extract was screened for hepatoprotective and antioxidant properties against CCl4 induced hepatic injury in rats. The hepatoprotection was assessed in terms of reduction in histological damage and changes in serum enzymes and metabolites. The pretreatment with the extract at 100 and 200 mg/kg body weight doses given orally for eight days prior to CCl4 caused significant restoration of altered biochemical changes due to CCl4 towards the normal in serum, liver and kidney. The extract treatment at 200 mg/kg body weight was found to be more potent than the standard silymarin at 100 mg/kg body weight in reversing most of the biochemical parameters. Histopathological studies complemented the results of biochemical estimations in providing a proof of hepatoprotective and antioxidant actions of the extract. The study provides a support to the ethnomedical use of E. axillare in India.     

Hepatoprotective effect of Hibiscus hispidissimus Griffith, ethanolic extract in paracetamol and CCl4 induced hepatotoxicity in Wistar rats

Hibiscus hispidissimus Griff. is used in tribal medicine of Kerala, the southern most state of India, to treat liver diseases. In the present study, the effect of the ethanolic extract of Hibiscus hispidissimus whole plant on paracetamol (PCM)-induced and carbon tetrachloride (CCl4)-induced liver damage in healthy Wistar albino rats was studied. The results showed that significant hepatoprotective effects were obtained against liver damage induced by PCM and CCl4 as evidenced by decreased levels of serum enzymes, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SAKP), serum bilirubin (SB) and an almost normal histological architecture of the liver of the treated groups compared to the toxin controls. The extract also showed significant antilipid peroxidant effects in vitro, besides exhibiting significant activity in quenching 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, indicating its potent antioxidant effects.     

Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents.

Caffeic acid and quercetin, the well-known phenolic compounds widely present in the plant kingdom, were investigated for their possible protective effects against paracetamol and CCl4-induced hepatic damage. Paracetamol at the oral dose of 1 g/kg produced 100% mortality in mice while pretreatment of separate groups of animals with caffeic acid (6 mg/kg) and quercetin (10 mg/kg) reduced the death rate to 20% and 30%, respectively. Oral administration of sub-lethal dose of paracetamol (640 mg/kg) produced liver damage in rats as manifested by the significant (P<0.01) rise in serum levels of aminotransferases (aspartate transaminase (AST) and alanine transaminase (ALT)) compared to respective control values. The serum enzyme values were significantly (P<0.01) lowered on pretreatment of rats with either caffeic acid (6 mg/kg) or quercetin (10 mg/kg). Similarly, the hepatotoxic dose of CCl4 (1.5 ml/kg; orally) also raised significantly (P<0.05) the serum AST and ALT levels as compared to control values. The same dose of the caffeic acid and quercetin was able to prevent CCl4-induced rise in serum enzymes. Caffeic acid and quercetin also prevented the CCl4-induced prolongation in pentobarbital sleeping time confirming their hepatoprotectivity. These results indicate that caffeic acid and quercetin exhibited hepatoprotective activity possibly through multiple mechanisms.     

Hepatoprotective and antioxidant activities of flowers of Calotropis procera (Ait) R. Br. in CCl4 induced hepatic damage

Hepatoprotective activity of 70% ethanolic extract of flowers of C. procera was studied against CCl4 induced hepatic injury in albino rats and mice. In addition, antioxidant activity was studied by in vitro models. Pre-treatment with 70% ethanolic extract (CPA) reduced the biochemical markers of hepatic injury like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, cholesterol, HDL and tissue glutathione (GSH) levels. Similarly pretreatment with CPA reduced the CCl4 induced elevation in the pentobarbitone sleeping time. Histopathological observations also revealed that pretreatment with CPA protected the animals from CCl4 induced liver damage. CPA demonstrated dose dependant reduction in the in vitro and in vivo lipid peroxidation induced by CCl4. In addition it showed dose dependant free radical scavenging activity. The results indicate that flowers of C. procera possess hepatoprotective property possibly because of its anti-oxidant activity. This property may be attributed to the quercetin related flavonoids present in the flowers of Calotropis procera.     

Hepatoprotective activity of Psidium guajava Linn. leaf extract

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.     

Hepatoprotective effect of Pergularia daemia (Forsk.) ethanol extract and its fraction

Ethanol extract and its ethanol fraction from aerial parts of P. daemia exhibited significant hepatoprotective effect against CCl4 induced hepatotoxicity in rats. Glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin, total cholesterol, total protein and albumin in serum indicated hepatoprotective effect of the ethanol extract and its ethanol fraction. Histopathological examination of liver sections confirmed that, pre-treatment with ethanol extract and its ethanol fraction prevented hepatic damage induced by CCl4. The results were comparable with the standard hepatoprotective drug silymarin. The extract and its fraction showed no signs of toxicity up to a dose level of 2000 mg/kg. It is suggested that, the presence of flavonoids in ethanol extract and its ethanol fraction may be responsible for hepatoprotective properties. High Performance Thin Layer Chromatography profile of flavonoids of bio-active extracts was developed using quercetin-3-glucoside as a marker. Results indicate hepatoprotective properties of ethanol extract of P. daemia.     

Hepato-protective potential of carotenoid meso-zeaxanthin against paracetamol, CCl4 and ethanol induced toxicity

Hepato-protective potential of carotenoid meso-zeaxanthin [(3R, 3'S)-beta, beta-carotene-3, 3'-diol] was studied using in vivo rat models. Paracetamol (3 g/kg body wt, orally), 20% ethanol (7.5 g/kg body wt, orally) and CCl4 (2.5 ml /kg, ip) were used as hepato toxins. Levels of marker enzymes of hepatic injury such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase, and serum bilirubin, which were drastically elevated by these hepato toxins were significantly decreased by meso-zeaxanthin pretreatment in a dose-dependent manner. Oxidative stress markers, tissue lipid peroxidation, conjugated dienes and tissue hydroperoxides, were high in the paracetamol treated control group animals, which were lowered by meso-zeaxanthin administration. Level of glutathione and antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, in liver tissue was increased by meso-zeaxanthin pretreatment compared to control group during alcohol and CCl4 induced hepatotoxicity. Hydroxyproline, an indicator of fibrosis in liver tissue, decreased remarkably by meso-zeaxanthin administration despite its notable elevation in ethanol treated rats. Histopathological analysis of liver tissue showed the hepatoprotective potential of meso-zeaxanthin.     

Effect of propolis extract on acute carbon tetrachloride induced hepatotoxicity

Ethanolic extract of propolis was administered to rats intoxicated by carbon tetrachloride. Administration of bolus dose of CCl4 (1.5 ml/kg, ip) resulted in elevation of serum transaminases and serum alkaline phosphatase activities. Levels of hepatic lipid peroxidation were significantly increased. On the contrary, there was significant decrease in hepatic reduced glutathione level. The propolis extract (100 and 200 mg/kg, po) exhibited recoupment in both pre- and post-treatment (prophylactic and curative studies) of biochemical changes induced by CCl4. The post treatment of 200 mg/kg, po extract showed most significant hepatoprotective effect. Histopathological studies showed damage in hepatocytes and disturbed chord arrangement after toxicant administration. Propolis extract (200 mg/kg, po) was found to be more effective in restoring CCl4 induced histopathological alterations.     

Effect of Azadirachta indica on paracetamol-induced hepatic damage in albino rats.

Azadirachta indica, a plant used widely in Ayurveda, has been reported to have anti-inflammatory, immunomodulatory and adaptogenic properties. The present study evaluates its hepatoprotective role. Fresh juice of tender leaves of Azadirachta indica (200 mg/kg body wt. p.o.) inhibited paracetamol (2 g/kg body wt. p.o.)-induced lipid peroxidation and prevented depletion of sulfhydryl groups in liver cells. There was an increase in serum marker enzymes of hepatic damage (aspartate transaminase, alanine transaminase and alkaline phosphatase) after paracetamol administration. Azadirachta indica pretreatment stabilized the serum levels of these enzymes. Histopathological observations of liver tissues corroborated these findings.     

Effect of Emblica officinalis (Gaertn) on CCl4 induced hepatic toxicity and DNA synthesis in Wistar rats

A single dose of CCl4 (1 ml/kg body weight, po in corn oil) increased the levels of SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase), LDH (lactate dehydrogenase), glutathione-S-transferase and depletion in reduced glutathione, glutathione peroxidase and glutathione reductase. It also caused enhancement in the levels of lipid peroxidation (LPO) and DNA synthesis. There was also pathological deterioration of hepatic tissue as evident from multivacuolated hepatocytes containing fat globules around central vein. The pretreatment of E. officinalis for 7 consecutive days showed a profound pathological protection to liver cell as depicted by univacuolated hepatocytes. Pretreatment with E. officinalis at doses of 100 and 200 mg/kg body weight, prior to CCl4 intoxication showed significant reduction in the levels of SGOT, SGPT, LDH, glutathione-S-transferase, LPO and DNA synthesis. There was also increase in reduced glutathione, glutathione peroxidase and glutathione reductase. The results suggest that E. officinalis inhibits hepatic toxicity in Wistar rats.     

Hepatoprotective activity of Leucas hirta against CCl4 induced hepatic damage in rats

Methanol and aqueous leaf extracts of L. hirta demonstrated hepatoprotective activity against carbon tetrachloride induced liver damage in rats. The parameters studied were serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum markers and decrease in total protein level reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with methanol and aqueous leaf extracts showed significant decrease in the levels of serum markers and increase in total protein indicating the protection of hepatic cells. The results revealed that methanol leaf extract followed by aqueous extract of L. hirta could afford significant protection against CCl4 induced hepatocellular injury.     

Hepatoprotective effect of Rhodiola imbricata rhizome against paracetamol-induced liver toxicity in rats

Rhodiola imbricata is a perennial herb of the family Crassulaceae, which has significant traditional usage as medicine and is also known to biosynthesize phytochemicals such as flavonoids, coumarins and phenyl glycosides. The present investigation was aimed to estimate the hepatoprotective activity of R. imbricata rhizome acetone extract against paracetamol (2 g/kg) induced liver toxicity. Paracetamol was administered to induce hepatic damage in Wistar rats. 200 and 400 mg/kg doses of rhizome acetone extract and silymarin (25 mg/kg) were used as treatment groups. The blood samples were analyzed for biochemical markers of hepatic injury and tissue samples were subjected for estimation of liver antioxidants and histopathological studies. Analysis of the extract treated rats (400 mg/kg) showed an elevation of superoxide dismutase (0.326 units/min/mg protein), catalase (185.03 μmole of H₂O₂ consumed/min/mg protein), glutothione peroxidase (19.26 mg GSH consumed/min/mg protein) and reduced glutathione (16.2 μmole of GSH/mg protein). Moreover, the biochemical parameters in serum like alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lipid profiles were also improved in treated groups compared to the control. The oral administration of different doses of rhizome acetone extract significantly protected the hepatic cells from damage. The hematological and biochemical parameters were also normal in extract treated rats compared to the control and standard (silymarin) groups. The HPLC analysis revealed the presence of some important phenolic compounds which could be responsible for the hepatoprotective activity. This study proved that R. imbricata could be taken as a good natural source of the hepatoprotective agent.     

Anti-trichomonal, biochemical and toxicological activities of methanolic extract and some carbazole alkaloids isolated from the leaves of Murraya koenigii growing in Nigeria

The methanolic extract of Murraya koenigii leaf was screened for toxicological and biochemical effects on rats because of the folkloric uses as an anti-dysentery and anti-diabetes. The extract was moderately toxic (LD(50)=316.23 mg/kg body weight) to rats and had appreciable effect on the liver and kidney at higher doses leading to liver inflammation. It had little or no effect on haematology and relative organ weight of lungs, heart and spleen. Acute doses (500 mg/kg) reduced significantly serum globulin, albumin, urea, glucose, total protein, aspartate transaminase (AST), and increased cholesterol and alanine transaminase (ALT) indicating hepatic injury. However, chronic administration for 14 days gave a significant (p<0.05) reduction in the serum cholesterol, glucose, urea, bilirubin, ALT and AST showing that the plant has hypoglycaemic and hepatoprotective effects after prolonged use. The activity demonstrated by some of the isolated carbazole alkaloids and their derivatives against Trichomonas gallinae confirmed that the anti-trichomonal activity of the leaf may be due to its carbazole alkaloids. The order of activity was C(18)>C(23)>C(13). Girinimbine and girinimbilol with IC(50) values of 1.08 and 1.20 microg/ml were the most active. Acetylation of girinimbilol and mahanimbilol improved their activities to 0.60 and 1.08 microg/ml.     

In vitro and in vivo hepatoprotective activity of Cissampelos pareira against carbon-tetrachloride induced hepatic damage

Administration of hydroalcoholic extract of Cissampelos pareira roots (CPRE) and standard drug silymarin in rats showed significant hepatoprotective action against CCl4 induced hepatotoxicity. Elevated serum marker enzymes of AST, ALT, ALP and serum bilirubin were significantly reduced to near normal level in CPRE treated rats. Lipid peroxidation level was decreased significantly in CPRE 100, 200, 400 mg/kg doses treatment groups. In case of antioxidant enzymes SOD, catalase levels were increased significantly after CPRE 200, 400 mg/kg doses, similarly it increased the enzyme levels of GST, GPx, and GSH. CPRE 200, 400 mg/kg decreased cholesterol level, and increased triglyceride level. In vitro hepatoprotective activity of the extract was evaluated at 20, 40, 60, 80 and 100 microg/ml concentration against CCl4 (1%) induced toxicity in freshly isolated rat hepatocytes. HepG2 cells showed significant dose dependent increase in percentage viability at the doses 20, 40, 60, 80 and 100 microg/ml of CPRE compared to CCl4 exposed HepG2 cells. Results of this study strongly demonstrate Cissampelos pariera having good hepatoprotective potential.     

Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats

This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane. Keywords: Hepatotoxicity, Haemotoxicity, Carbon tetrachloride, Cnidoscolus aconitifolius, Rats.     

Hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract against carbon tetrachloride-induced hepatocyte damage in Cyprinus carpio

The present study aims to evaluate the hepatoprotective and antioxidant effects of Hibiscus sabdariffa extract on the carbon tetrachloride (CCl(4))-induced hepatocyte damage in fish and provide evidence as to whether it can be potentially used as a medicine for liver diseases in aquaculture. H. sabdariffa extract (100, 200, and 400?μg/mL) was added to the carp primary hepatocyte culture before (pre-treatment), after (post-treatment), and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4). CCl(4) at 8?mM in the culture medium produced significantly elevated levels of lactate dehydrogenase (LDH), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT), and malondialdehyde (MDA) and significantly reduced levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Pre-treatment and pre- and post-treatment of the hepatocytes with H. sabdariffa extract significantly reduced the elevated levels of LDH, GOT, GPT, and MDA and increased the reduced activities of SOD and GSH-Px in a dose-dependent manner; post-treatment did not show any protective effect. The results suggest that H. sabdariffa extract can be potentially used for preventing rather than curing liver diseases in fish.     

Ocimum sanctum aqueous leaf extract provides protection against mercury induced toxicity in Swiss albino mice

HgCl2 (5.0 mg/kg body weight) induced toxicity led to significant elevation of lipid peroxidation (LPO) level but decline in the glutathione content in liver of Swiss albino mice. In serum of HgCl2 treated mice there was significant elevation in serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities but significant decline in the alkaline phosphatase activity. Animals treated with O. sanctum extract (10 mg/kg body weight, po) before and after mercury intoxication showed a significant decrease in LPO level, SGOT and SGPT activities and increase in serum alkaline phosphatase activity and glutathione (GSH) content. Ocimum treatment alone did not alter SGOT, SGPT and alkaline phosphatase activities but significantly enhanced reduced glutathione. The results suggest that oral administration of Ocimum extract provides protection against HgCl2 induced toxicity in Swiss albino mice.