Investigation of hepatoprotective activity of Cyathea gigantea (Wall. ex. Hook.) leaves against paracetamol-induced hepatotoxicity in rats

Objective

To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea (C. gigantea) against paracetamol induced liver damage in rats.

Methods

The hepatoprotective activity for plant extract was investigated for paracetamol induced hepatoxicity in rats. Wistar albino rats of either sex were divided into five groups of 6 animals each and are given orally the following treatment for seven days. The normal control group was given 1% Na.CMC 1 mL/kg bw, p.o. Paracetamol at dose of 1 g/kg bw, p.o. was given as toxic dose for inducing hepatotoxicity. Silymarin (50 mg/kg, p.o.) was given as reference standard. Two doses of C. gigantea extract i.e., 100 mg/kg, p.o. and 200 mg/kg, p.o. were tested for hepatoprotective activity. The treatment was given for seven days and after 24 h of last treatment blood was collected from retro-orbital plexus and analysed for various serum parameters like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin (TB) and total protein (TP) in different groups.

Results

The paracetamol intoxication lead to histological and biochemical deteriorations. The treatment with methanolic leaf extract of C. gigantea reduced the elevated levels of SGOT, SGPT, ALP, TB and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extract of C. gigantea.

Conclusions

The methanolic extract of leaves of C. gigantea at doses of 100 mg/kg bw and 200 mg/kg bw have significant effect on liver of paracetamol induced hepatotoxicity model in rats.     

Calotropis procera latex affords protection against carbon tetrachloride induced hepatotoxicity in rats

In the present study, latex of Calotropis procera possessing potent antioxidant and anti-inflammatory properties was evaluated for its hepatoprotective effect against carbon tetrachloride (CCl(4)) induced hepatotoxicity in rats. Subcutaneous injection of CCl(4,) administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and tumor necrosis factor alpha (TNF-alpha). Histological analysis of the liver of these rats revealed marked necro-inflammatory changes that were associated with increase in the levels of TBARS, PGE(2) and catalase and decrease in the levels of glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Daily oral administration of aqueous suspension of dried latex (DL) of Calotropis procera at 5, 50 and 100mg/kg doses produced a dose-dependent reduction in the serum levels of liver enzymes and inflammatory mediators and attenuated the necro-inflammatory changes in the liver. The DL treatment also normalized various biochemical parameters of oxidative stress. Our study shows that the antioxidant and anti-inflammatory effects of DL and silymarin were comparable and suggests that DL could be used as a hepatoprotective agent.     

Hepatoprotective potential of Aloe barbadensis Mill. against carbon tetrachloride induced hepatotoxicity

Aloe barbadensis Mill. Syn. Aloe vera Tourn. ex Linn.(Liliaceae) has been used in variety of diseases in traditional Indian system of medicine in India and its use for hepatic ailments is also documented. In the present study an attempt has been made to validate its hepatoprotective activity. The shade dried aerial parts of Aloe barbadensis were extracted with petroleum ether (AB-1), chloroform (AB-2) and methanol (AB-3). The plant marc was extracted with distilled water (AB-4). All the extracts were evaluated for hepatoprotective activity on limited test models as hexobarbitone sleep time, zoxazolamine paralysis time and marker biochemical parameters. AB-1 and AB-2 were observed to be devoid of any hepatoprotective activity. Out of two active extracts (AB-3 and AB-4), the most active AB-4 was studied in detail. AB-4 showed significant hepatoprotective activity against CCl4 induced hepatotoxicity as evident by restoration of serum transaminases, alkaline phosphatase, bilirubin and triglycerides. Hepatoprotective potential was confirmed by the restoration of lipid peroxidation, glutathione, glucose-6-phosphatase and microsomal aniline hydroxylase and amidopyrine N-demethylase towards near normal. Histopathology of the liver tissue further supports the biochemical findings confirming the hepatoprotective potential of AB-4. The present study shows that the aqueous extract of Aloe barbadensis is significantly capable of restoring integrity of hepatocytes indicated by improvement in physiological parameters, excretory capacity (BSP retention) of hepatocytes and also by stimulation of bile flow secretion. AB-4 did not show any sign of toxicity up to oral dose of 2 g/kg in mice.     

Protective effects of puerarin on carbon tetrachloride-induced hepatotoxicity

Puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicine for thousands of years. The purpose of this study was to investigate the protective effects of puerarin against hepatotoxicity induced by carbon tetrachloride (CCl4) and the mechanism of its hepatoprotective effect. In mice, pretreatment with puerarin prior to the administration of CCl4 significantly prevented the increased serum enzymatic activity of alanine aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. In addition, pretreatment with puerarin significantly prevented both the depletion of reduced glutathione (GSH) content and the decrease in glutathione S-transferase (GST) activity in the liver of CCl4-intoxicated mice. Hepatic GSH levels and GST activity were increased by treatment with puerarin alone. CCl4-induced hepatotoxicity was also prevented, as indicated by liver histopathology. The effects of puerarin on cytochrome P450 (CYP) 2E1, the major isozyme involved in CCl4 bioactivation, were also investigated. Treatment of the mice with puerarin resulted in a significant decrease in the CYP2E1-dependent aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the CYP2E1 protein levels were also lowered. Puerarin exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in mouse liver homogenates, and on superoxide radical scavenging activity. These results suggest that the protective effects of puerarin against the CCl4-induced hepatotoxicity possibly involve mechanisms related to its ability to block CYP-mediated CCl4 bioactivation, induction of GST activity and free radical scavenging effects.     

腰骨藤的植物化学和药理学研究进展(英文)

Ichnocarpus frutescens R. Br. (Apocynaceae), is a woody climbing shrub, found almost in all parts of India. In India, tribes used this plant as a substitute of Indian Sarsaparilla (Hemidesmus indicus) for the treatment of atrophy, convulsions, cough, delirium, dysentery, measles, splenomegaly, tuberculosis, tumor, diabetes as a lactogogue, antipyretic, demulcent, diaphoretic and in skin diseases. Phytochemical investigations indicate that 28 compounds reported from the plant belong to various chemical category viz. phytosterol, triterpenes, flavonoids and various other phenolic compounds. Pharmacological activities of different parts of the plant reported include antiurolithiatic, hepatoprotective, antioxidant, analgesic, antipyretic, anti-inflammatory, antidiabetic, antihyperlipi-demic and antitumor activity. In the present review the literature data on the phytochemical and biological investigations on the I. frutescens are summarized up to March 2011.     

Comparative Anti-Inflammatory and Hepatoprotective Activities of Astragalus Gummifer Labill Herb and Roots in Rats

Background

The Astragalus gummifer (F. Fabaceae), herb and roots were studied for anti-inflammatory and hepatoprotective activities.

Materials and method

The alcoholic extracts of Astragalus gummifer (F. Fabaceae), herb (AGHE), and roots (AGRE), were used for anti-inflammatory and hepatoprotective activities in Wister rats. The effects of AGHE and AGRE were compared with the standard drugs Phenylbutazone and silymarin, for anti-inflammatory and hepatoprotective activities respectively.

Result

Both extracts showed significant anti-inflammatory activity (P< 0.001). AGRE showed comparatively more significant hepatoprotective activity (P< 0.001), than AGHE (P< 0.05); at doses of 250 and 500 mg/kg body weight as manifested by lowering the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin. The hepatoprotective activity was, also, supported by total protein (TP), malondialdehyde (MDA), nonprotein sulfhydryls (NP-SH), and histo-pathological studies of liver tissue.

Discussion

To the best of our knowledge, this is the first report of the anti-inflammatory and hepatoprotective activities of Astragalus gummifer. The results of present studies indicated that both AGHE and AGRE can be used in inflammatory conditions, while investigation supports the use of AGRE in cases that hepatoprotection are required in the hepatotoxic conditions. More supportive studies are required before clinical recommendation.     

Hepatoprotective effects of Eclipta alba on subcellular levels in rats

The hepatoprotective effect of the ethanol/water (1:1) extract of Eclipta alba (Ea) has been studied at subcellular levels in rats against CCl₄-induced hepatotoxicity. Ea significantly counteracted CCl₄-induced inhibition of the hepatic microsomal drug metabolising enzyme amidopyrine N-demethylase and membrane bound glucose 6-phosphatase, but failed to reverse the very high degree of inhibition of another drug metabolising enzyme aniline hydroxylase. The loss of hepatic lysosomal acid phosphatase and alkaline phosphatase by CCl₄ was significantly restored by Ea. Its effect on mitochondrial succinate dehydrogenase and adenosine 5'-triphosphatase was not significant. The study shows that hepatoprotective activity of Ea is by regulating the levels of hepatic microsomal drug metabolising enzymes.     

Hepatoprotection by chemical constituents of the marine brown alga Spatoglossum variabile: A relation to free radical scavenging potential

Context: In the course of searching hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine brown alga Spatoglossum variabile Figaro et DE Notar (Dictyoaceae) against CCl₄-induced liver damage in Wistar rats was investigated. The compounds were first investigated for in vitro radical scavenging potential and were also tested for β-glucuronidase inhibition to further explore the relationship between hepatoprotection and antiradical potential.

Methods: The compounds cinnamic acid esters 1 and 2 and aurone derivatives 3 and 4 were first investigated for in vitro radical scavenging potential against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and superoxide anion radicals. In vivo hepatoprotective studies were performed in seven groups (n = 6) of Wistar rats. The test groups were pretreated with compounds (10?mg/kg body weight, po) orally for 30?min before the intraperitoneal administration of a dose of 20% CCl₄ diluted with dietary cooking oil. Moreover, compounds were also tested for β-glucuronidase inhibition to explore the relationship between hepatoprotection and radical scavenging potential.

Results: The test compounds 1–4 were found to exhibit antiradical activity against 1,1-diphenyl-2-picrylhydrazyl radicals with IC₅₀ values ranging between 54 and 138 µM, whereas aurone derivatives 3 and 4 additionally exhibited superoxide anion scavenging effects with IC₅₀ values of 95 and 87 µM, respectively. In addition, these compounds were found to be weak inhibitors of xanthine oxidase (IC₅₀ ≥1000 µM). In animal model, pretreatment with compounds 2–4 significantly blocked the CCl₄-induced increase in the levels of the serum biochemical markers.

Conclusion: It appears that the hepatoprotection afforded by these compounds was mainly due to their radical scavenging activity that protected the cells from the free radicals generated by CCl₄-induced hepatotoxicity.     

Antiproliferative and hepatoprotective activity of metabolites from Corynebacterium xerosis against Ehrlich Ascites Carcinoma cells

ObjectiveTo find out the effective anticancer drugs from bacterial products, petroleum ether extract of Corynebacterium xerosis.MethodsAntiproliferative activity of the metabolite has been measured by monitoring the parameters like tumor weight measurement, tumor cell growth inhibition in mice and survival time of tumor bearing mice, etc. Hepatoprotective effect of the metabolites was determined by observing biochemical, hematological parameters.ResultsIt has been found that the petroleum ether extract bacterial metabolite significantly decrease cell growth (78.58%; P<0.01), tumor weight (36.04 %; P<0.01) and increase the life span of tumor bearing mice (69.23%; P<0.01) at dose 100 mg/kg (i.p.) in comparison to those of untreated Ehrlich ascites carcinoma (EAC) bearing mice. The metabolite also alters the depleted hematological parameters like red blood cell, white blood cell, hemoglobin (Hb%), etc. towards normal in tumor bearing mice. Metabolite show no adverse effect on liver functions regarding blood glucose, serum alkaline phosphatases, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase activity and serum billirubin, etc. in normal mice. Histopathological observation of these mice organ does not show any toxic effect on cellular structure. But in the case of EAC bearing untreated mice these hematological and biochemical parameters deteriorate extremely with time whereas petroleum ether extract bacterial metabolite receiving EAC bearing mice nullified the toxicity induced by EAC cells.ConclusionStudy results reveal that metabolite possesses significant antiproliferative and hepatoprotective effect against EAC cells.     

Hepatoprotective effects of Yulangsan polysaccharide against isoniazid and rifampicin-induced liver injury in mice

Ethnopharmacological relevance

Yulangsan polysaccharide (YLSPS) is often used in popular folk medicine in the Guangxi Zhuang Autonomous Region of China as a chief ingredient of Millettia pulchra, which is used as an hepatic protection, anti-aging and memory improving agent. In this study, the hepatoprotective effects of YLSPS against isoniazid (INH) or rifampicin and isoniazid (RFP+INH)-induced liver injury were investigated in mice.

Materials and methods

The liver injury was induced by intragastric administration of INH or RFP+INH daily for 10 days. During the experiment, the model group received INH or RFP+INH only, and the normal control group received an equal volume of saline. Treatment groups received not only INH or RFP+INH but also the corresponding drugs, DDB (200 mg/kg/day) or YLSPS (100, 200, and 400 mg/kg/day) 2 h after the administration of INH or RFP+INH.

Results

Analysis experiments showed that YLSPS significantly alleviated liver injury as indicated by the decreased levels of ALT and AST and the increased levels of SOD, GSH and GSH-Px. Moreover, YLSPS could effectively reduce the pathological tissue damage. The research on the mechanisms underlying the hepatoprotective effect showed that YLSPS was able to reduce lipid peroxidation and activate the anti-oxidative defense system.

Conclusion

Our results show that YLSPS is effective in attenuating hepatic injury in the INH or RFP+INH-induced mouse model, and could be developed as a new drug for treatment of liver injury.