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.     

Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats

The study was aimed to investigate the antioxidant activity of Cytisus scoparius L. (Family: Leguminosae) on CCl(4) (carbon tetrachloride) treated oxidative stress in Wistar albino rats. CCl(4) injection induced oxidative stress by a significant rise in serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate transaminases (SGPT), lactate dehydrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) along with reduction of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST) and glutathione reductase (GRD). Pretreatment of rats with different doses of plant extract (250 and 500mg/kg) significantly lowered SGOT, SGPT, LDH and TBARS levels against CCl(4) treated rats. GSH and hepatic enzymes like SOD, CAT, GPx, GRD, and GST were significantly increased by treatment with the plant extract, against CCl(4) treated rats. The activity of extract at the dose of 500mg/kg was comparable to the standard drug, silymarin (25mg/kg). Based on these results, it was observed that Cytisus scoparius extract protects liver from oxidative stress induced by CCl(4) in rats and thus helps in evaluation of the traditional claim on this plant.     

Hepatoprotective effect of acetonic and methanolic extracts of Heterotheca inuloides against CCl4-induced toxicity in rats

A model of hepatotoxicity by carbon tetrachloride (CCl₄) in rats was used in order to evaluate the protective potential of the acetonic and methanolic extracts of Heterotheca inuloides. Pretreatment with the two H. inuloides extracts attenuated the increase in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) observed in CCl₄-induced liver injury. The protective effect was confirmed by the analysis of tissue slides stained with hematoxylin-eosin and periodic acid/Schiff’s reagent. Additionally, the two extracts are scavengers to the superoxide radical as was observed by electron paramagnetic resonance. Due to the fact that the methanolic extract resulted in a better protective effect in the previous experiments, it was used to investigate in more detail the mechanism of hepatoprotection. Quercetin, one of the main components of the extract, with known hepatoprotective and antioxidant activity was used as a positive control. Pretreatment of animals with the methanolic extract or quercetin, was associated with the prevention of 4-hydroxynonenal and 3-nitrotyrosine increase in the liver, two markers of oxidative stress. Furthermore, the decrease in the activity of several antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase in CCl₄-induced liver injury was alleviated by the pretreatment with H. inuloides methanolic extract or quercetin. These results suggest that the hepatoprotective capacity of H. inuloides methanolic extract is associated with its antioxidant properties, which would also explain the biomedical properties attributed to this plant.     

Antioxidant,hepatoprotective and hypolipidemic effects of methanolic root extract of Cassia singueana in rats following acute and chronic carbon tetrachloride intoxication

ObjectiveTo evaluate in vivo antioxidant and hepatoprotective activities of the methanolic extract of the root of Cassia singueana in rats following acute and chronic carbon tetrachloride intoxication.MethodsMalondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin as indices of liver damage and lipid peroxidation were detected in rats after intraperitoneal administration of extract (5 mg/kg).ResultsThe liver, kidney and heart showed significant reduction (P<0.05) in the levels of MDA from (0.18±0.04), (0.23±0.07) and (0.26±0.10) nmol/mg respectively in the CCl₄ control to (0.15±0.03), (0.17±0.04) and (0.17±0.07) nmol/mg protein in groups pre-treated with the extract for three days at 5 mg/kg). Similarly, compared to the CCl₄ control, significant reduction (P<0.05) in serum AST, ALT and bilirubin as well as in level of total cholesterol and MDA with concomitant increase in HDL cholesterol, superoxide dismutase and catalase levels when CCl₄-intoxicated rats were treated with Cassia singueana root extract for two weeks.ConclusionsThese results suggest that methanolic extract of Cassia singueana contain potent antioxidant compounds that can offer significant protection against hepatic and oxidative injuries.     

Hepatoprotective activity of scopoletin, a constituent ofSolanum lyratum

Scopoletin (7-hydroxy-6-methoxycoumarin), a coumarin, was isolated from the aerial part ofSolanum lyratum Thunb. by the activity-guided fractionation employing carbon tetrachloride-intoxicated primary cultured rat hepatocytes as a screening system. Its hepatoprotective activity was first evaluated by measuring the release of glutamic pyruvic transaminase and sorbitol dehydrogenase from carbon tetrachloride-intoxicated rat hepatocytes into the culture medium. Scopoletin significantly reduced the releases of glutamic pyruvic transaminase and sorbitol dehydrogenase from the carbon tetrachloride-intoxicated primary cultured rat hepatocytes by 53% and 58%, respectively, from the toxicity in a dose-dependent manner over concentration ranges of 1 μM to 50 μM. Further studies revealed that at the concentration of 10 μM, scopoletin significantly preserved glutathione content by 50% and the activity of superoxide dismutase by 36% and also inhibited the production of malondialdehyde to the degree as seen in the control.     

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

Objective

To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.

Methods

Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.

Results

The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.

Conclusions

The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.     

Modification of C2 functional group on asiatic acid and the evaluation of hepatoprotective effects

For the development of novel hepatoprotective agents, C2 functional group on asiatic acid was modified, and evaluated for their hepatoprotective effects. Among prepared compounds, compounds 10 and 14 showed better hepatoprotective effects compared to silymarin.     

Scientific evaluation of the chronic toxicity of the herbal medicine CGX in beagle dogs

CGX is a potential hepatoprotective herbal medicine used to treat various chronic liver disorders. The purpose of the study was to evaluate the pharmaceutical safety of CGX via a systemic 13-week repeated dose toxicity test in beagle dogs. Male and female beagle dogs were divided into four groups and two animals each from the control and high-dose group (400 mg/kg) were allocated into recovery groups. The dogs were administered with CGX (0, 100, 200, 400 mg/kg) for 13 weeks. During the experimental period, the dogs were observed for signs of gross toxicity and for behavioral changes; body weight and food consumption were measured. An ophthalmologic examination and urinalysis were performed at 0 and 13th week and blood biochemistry and hematological parameters analyses were performed at 0, 6th, and 13th week. A histopathological examination was also performed at the end of the experiment. There were no CGX-induced abnormalities in clinical signs, organ weights, food consumption, hematological, urine, and blood biochemical parameters, or histopathological findings in any of the groups during or after the 13 weeks. We demonstrated the safety of CGX for 13-week repeated dose and considered that it is safe for chronic clinical use.     

CGX,a traditional Korean medicine ameliorates concanavalin A-induced acute liver injury

Concanavalin A (Con A)-induced acute liver injury model is well established as a model of T cell-mediated liver injury, in which T cells and NKT cells exert their cytotoxicity towards liver cells. In this study, we investigated the protective effects of CGX, a traditional Korean medicine against Con A-induced liver injury and its underlying mechanisms. After pretreatment with CGX (po, 50, 100 or 200 mg/kg) or distilled water once daily during 7 days, Con A (15 mg/kg) was injected intravenously. Thereafter serum level of AST and ALT, lipid peroxidation and cytokines in the liver tissue, and immune cell population in blood and the spleen were analyzed. CGX treatment reduced serum ALT, AST level in a dose-dependent manner. CGX treatment significantly decreased the lipid peroxidation and glutathione depletion in the liver tissue, and also lowered tissue levels of tumor necrotic factor-α and interferon-γ. CGX treatment attenuated the compositional alteration of Tc, Th, NKT, and B cells in blood as well as in the spleen. These results suggest that CGX has hepatoprotective property against Con A-induced liver injury through antioxidant action and immune regulation.     

Ethnopharmacology,phytochemistry and pharmacology of Tephrosia purpurea简

Tephrosiapurpurea （L.） Pers. is popularly known as ＇Sarapunkha＂ in classical Ayurvedic texts. It is a perennial plant belonging to the family Fabaceae, and occurs throughout the Indian subcontinent. T. purpurea is traditionally used to treat spleenomegaly, cirrhosis, cough and cold, abdominal swelling and as an antidote in the Ayurvedic system of medicine. Phytochemical investigations indicate the presence of semiglabrin, pongamole, lanceolatins A and B, rutin, lupeol, and β-sitosterol. Flavonoids including （＋）-tephrorin A and B, （＋）-tephrosone, an isoflavone, 7, 4＇-dihydroxy-3＇, 5＇-dimethoxyisoflavone and a chalcone, （＋）-tephropurpurin were isolated from the whole plant. Pharmacological activities of different parts of the plant reported include anti-inflammatory, antiulcer, antimicrobial, antioxidant, antiallergic, antidiabetic, hepatoprotective, antitumor and insect repellent activity. In the present review, the literature on the phytochemical and pharmacological investigations of Tephrosia purpurea （L.） Pers. are summarized to August, 2012.