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.     

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.     

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 activity of Haridradi ghrita on carbon tetrachloride-induced liver damage in rats

Haridradi ghrita, a ghee based polyherbal formulation, (50, 100, 200 and 300 mg/kg) significantly lowered marker enzymes (SGPT, SGOT, ALP) and bilirubin in serum and liver peroxide, superoxide dismutase and catalase in liver homogenate following CCl4 (0.7 ml/kg, ip) toxicity. The protective effect was further supported by reversal of CCl4 induced histological changes. The results demonstrate significant hepatoprotective action of H. ghrita in CCl4 damaged rats.     

Hepatoprotective activity of Hemidesmus indicus R. br. in rats

Treatment of rats with paracetamol and CCl4 produced a significant increase in the levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total and direct bilirubin. Rats pretreated with methanolic extract of roots of H. indicus (100-500 mg/kg body weight, po) exhibited rise in the levels of these enzymes but it was significantly less as compared to those treated with paracetamol or CCl4 alone. The results of methanolic extract of H. indicus were comparable with the standard hepatoprotective agent silymarin (100 mg/kg). Maximum hepatoprotective effect was found to be at the dose of 250 mg/kg body weight in case of CCl4 induced hepatic damage while 500 mg/kg body weight in case of paracetamol induced hepatic damage. The results suggest that methanolic extract of H. indicus roots possesses a potential antihepatotoxic activity.     

Protective effect of Aquilegia vulgaris (L.) on carbon tetrachloride-induced oxidative stress in rats

The ethyl ether extract of A. vulgaris inhibited in vitro microsomal lipid peroxidation (IC50 58.8 microg/ml) and showed moderate ability to scavenge superoxide radicals and to chelate iron ions. The extract (100 mg/kg body weight, po) decreased uninduced and enzymatic microsomal lipid peroxidation in the liver of male rats pretreated with CCl4 (1 ml/kg body weight) by 27 and 40%, respectively. Activity of antioxidant and related enzymes (catalase and glucose-6-phosphate dehydrogenase) inhibited by CCl4 was significantly restored after administration of the extract. The extract itself significantly enhanced superoxide dismutase activity. There was no effect of the extract on hepatic glutathione level and cytochrome P450 content, both were decreased by CCl4. Neither CCl4 nor the tested extract affected activities of NADPH-cytochrome P450 reductase and two monooxygenases, aniline hydroxylase and aminopyrine n-demethylase. It can be concluded that the protective effect of the A. vulgaris extract in CCl4-induced liver injury is mediated by inhibition of microsomal lipid peroxidation and restoring activity of some antioxidant and related enzymes.     

Antioxidant effects and hepatoprotective activity of 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots on CCl4-induced liver damage

We investigated hepatoprotective activity and antioxidant effect of the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene that purified from Morus bombycis Koidzumi roots against CCl4-induced liver damage in rats. The 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene displayed dose-dependent superoxide radical scavenging activity (IC50 = 430.2 microg/ml), as assayed by the electron spin resonance (ESR) spin-trapping technique. The increase in aspartate aminotransferase (AST) activities in serum associated with carbon tetrachloride (CCl4)-induced liver injury was inhibited by 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene and at a dose of 400 - 600 mg/kg samples had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene is a potent antioxidant with a liver protective action against CCl4-induced hepatotoxicity.     

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.     

The protective effects of Curcuma longa Linn. extract on carbon tetrachloride-induced hepatotoxicity in rats via upregulation of Nrf2

This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl4 administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl4 (20mg/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 CCl4-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 CCl4-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 CCl4-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 CCl4-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.     

Hepatoprotective action of abhrak bhasma, an ayurvedic drug in albino rats against hepatitis induced by CCl4

Abhrak bhasma is a commonly used ayurvedic drug against many diseases including hepatitis. It is tested in albino rats using a model of hepatitis induced by a single dose of CCl4 (3 ml/kg body wt). Different doses of abhrak bhasma (10, 20, 30 and 40 mg/kg body wt) were tested to decide the dose related hepatoprotective efficacy. The centrolobular necrosis induced by single dose of CCl4 was reduced significantly by abhrak bhasma (10 mg) and liver histology was also protected by 20 mg dose. Liver acid lipase activity was lowered, while alkaline and lipoprotein lipase activities were elevated due to treatment of single dose of CCl4. Abhrak bhasma counteracted the action of CCl4 on liver lipolytic enzymes. CCl4 did not alter the kidney histologically. Activities of three lipases of rat kidney (acid, alkaline and lipoprotein lipases) were reduced by CCl4 treatment and were reversed by administration of abhrak bhasma. Acid lipase activity of rat adipose tissue was reduced by CCl4 treatment. On the contrary alkaline, lipoprotein and hormone sensitive lipases were enhanced after 24 hr of administration of CCl4. Acid lipase activity was raised by administration of different doses of abhrak bhasma concurrent with CCl4. Abhrak bhasma treatment along with CCl4 enhanced alkaline lipase activity at 10 and 20 mg dose and later it was reduced at 30 and 40 mg doses and came to normal levels. Lipoprotein and hormone sensitive lipases were reduced by the counteraction of increasing doses of abhrak bhasma.     

The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats

In this study, the aphrodisiac activities of Crocus sativus stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract (80, 160 and 320 mg/kg body wt.), crocin (100, 200 and 400 mg/kg body wt.), safranal (0.1, 0.2 and 0.4 ml/kg), sildenafil (60 mg/kg body wt., as a positive control) and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320 mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.     

Psychopharmacological profile of hydro-alcoholic extract of Euphorbia neriifolia leaves in mice and rats

The leaf extract of E. neriifolia significantly reduced apomorphine-induced stereotypy in mice at all doses (100, 200, 400 mg/kg body weight) in mice and rats and was devoid of catalepsic effect thereby, suggesting specific dopaminergic receptor modulating activity. The extract (400 mg/kg) potentiated pentobarbitone-induced hypnosis. It showed protection against maximal electro-shock-induced convulsion at 400 mg/kg. E. neriifolia leaf extract had anxiolytic action at 400 mg/kg by increasing the percentage of time spent in open arm in elevated plus-maze. The extract did not reverse scopolamine-induced amnesia on elevated plus-maze. It increased transfer latency at 200 and 400 mg/kg and also in combination with scopolamine. These results indicated anti-anxiety, anti-psychotic and anti-convulsant activity of E. neriifolia leaf extract in mice and rats. Phytochemical study showed the presence of steroidal saponin, reducing sugar, tannins, flavonoids in the crude leaf extract     

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.     

Protective mechanism of Lygodium flexuosum extract in treating and preventing carbon tetrachloride induced hepatic fibrosis in rats

The protective effect of Lygodium flexuosum extract in preventive and curative treatments of CCl(4) induced fibrosis was quantified. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100 gm rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of L. flexuosum n-hexane extract (200 mg/kg, p.o) were administered for 10 weeks. In curative treatment L. flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with the n-hexane extract (200 mg/kg) reduced the mRNA levels of proinflammatory cytokines, growth factors and other signaling molecules, which are involved in hepatic fibrosis. The expression levels of tumor necrosis factor-alpha, interleukin-1beta, transforming growth factor-beta1, procollagen-I, procollagen-III and tissue inhibitor of metalloproteinase-1 were elevated during carbon tetrachloride administration and reduced the levels to normal by the treatment with the extract treatment. The increased levels of matrix metalloproteinase-13 in extract treated rats were indicative of the protective action of L. flexuosum n-hexane extract. In conclusion, L. flexuosum n-hexane extract functions as a potent fibrosuppresant, effectively reverses carbon tetrachloride-induced hepatic fibrosis in curative treatment and reduces the effects of ongoing toxic liver injury in preventive treatment by promoting extracellular matrix degradation in the fibrotic liver.     

Hepatoprotective and antioxidant effects of Morus bombycis Koidzumi on CCl4-induced liver damage

The antioxidant activity and liver protective effect of Morus bombycis Koidzumi were investigated. Aqueous extracts of M. bombycis Koidzumi had higher superoxide radical scavenging activity than other types of extracts. The aqueous extract at a dose of 100 mg/kg showed significant hepatoprotective activity when compared with that of a standard agent. The biochemical results were confirmed by histological observations indicating that M. bombycis Koidzumi extract together with CCl(4) treatment decreased ballooning degeneration. The water extract recovered the CCl(4)-induced liver injury and showed antioxidant effects in assays of FeCl(2)-ascorbic acid-induced lipid peroxidation in rats. Based on these results, we suggest that the hepatoprotective effect of the M. bombycis Koidzumi extract is related to its antioxidative activity.     

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.     

Destruction of hepatic mixed-function oxygenase parameters by CCl4 in rats following acute treatment with chlordecone, Mirex, and phenobarbital

Previous work has established the marked potentiation of CCl4 hepatoxicity by prior exposure to chlordecone (CD). This study was conducted to determine if prior exposure to CD results in enhancement of CCl4-induced destruction of the hepatic microsomal mixed-function oxygenase (MFO) system. Male Sprague-Dawley rats received a single oral dose of CD (10 mg/kg) or corn oil vehicle alone (1 ml/kg) 24 hr prior to a single ip injection of CCl4 (0-100 microliter/kg). Mirex (M; 10 mg/kg) and phenobarbital (PB; 80 mg/kg/day for two days) were used as negative and positive controls respectively for the potentiation of CCl4 hepatotoxicity. Hepatotoxicity was evaluated 24 hrs after CCl4 administration by elevations of three serum enzymes (GPT, GOT, and ICD). The key hepatic microsomal MFO parameters measured were microsomal protein, cytochrome P-450 content, glucose-6-phosphatase (G-6-Pase), and aminopyrine demethylase (APD). As previously demonstrated using a subchronic dietary pretreatment protocol, CD potentiated CCl4 hepatotoxicity over a range of CCl4 doses to a greater extent than PB or M, as judged by elevations in serum enzymes. PB caused the greatest increase in total P-450 content and the greatest increase in CCl4-mediated destruction of microsomal protein and APD activity. M caused the least destruction of total hepatic cytochrome P-450, despite the same level of cytochrome P-450 as in the PB group. CD treatment caused the greatest decrease in G-6-Pase activity in comparison to PB or M pretreatments and a similar degree of P-450 destruction as observed with the PB group. These findings suggest that in general, CCl4-induced destruction of hepatic MFO parameters measured in this study is disproportional to the known degree of potentiated hepatotoxicity by the pretreatments and does not accurately reflect the potentiation of CCl4 hepatotoxicity by CD.     

S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats

This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.     

Haematopoietic properties of ethanolic extract of Ageratum conyzoides (Goat weed) in Albino rats.

The potential haematological effects associated with the administration of ethanolic leaf extract of Ageratum conyzoides was investigated in rats. 27 rats were randomly divided into four groups. The first group had 6 rats and served as control, the remaining 3 experimental groups and had 7 rats each. These later groups were gavaged with the extract of Ageratum conyzoides in concentrations of 200 mg/kg, 400 mg/kg and 500 mg/kg respectively for 30 days at a dose of 0.1 ml/body weight. The control group was gavaged with 0.9% sodium chloride at a dose of 0.1 m1/body weight as placebo. The extract at the doses administered was found to increase in a dose-related fashion PCV and Hb ([P < 0.01] for 200 mg/kg and [P < 0.001] for 400 mg/kg and 500 mg/kg), RBC ([P < 0.05] for 400 mg/Kg and 500 mg/kg) and marginal increases that were not significant for 200 mg/kg); MCH and MCV ([P < 0.05] and [P < 0.01] for 400mg/kg and 500mg/kg respectively) 200 mg/kg was not significant. MCHC recorded no significant change. WBC recorded marginal increases that were not significant, similarly, the differential white blood cell recorded marginal increases that were not significant, except lymphocytes that recorded significant increase in group 4 [P < 0.05]. Marginal Decreases in body weight were also observed, these decreases were however not significant. The result of this study thus indicate haematopoietic potentials of the extract and could possibly remedy anaemia.     

Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats

The present study examined the effect of water extract (200 mg/kg body weight) of Rosmarinus officinalis L. in streptozotocin (STZ)-induced diabetic rats for 21 days. The hepatoprotective effects were investigated in the liver tissues sections. There was a significant increase in serum liver biochemical parameters (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase), accompanied by a significant decrease in the level of total protein and albumin in the STZ-induced rats when compared with that of the normal group. The high-dose treatment group (200 mg/kg body wt) significantly restored the elevated liver function enzymes near to normal. This study revealed that rosemary extracts exerted a hepatoprotective effect. The results indicate that the extract exhibits the protective effect on tissues and prove its potentials as an antidiabetic agent.