Protective effect of diarylheptanoids from Curcuma comosa on primary rat hepatocytes against t -butyl hydroperoxide-induced toxicity (original) (raw)
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Pharmaceutical Sciences Asia
Curcuma comosa Roxb. (C. comosa, Zingiberaceae) is a medicinal herb containing diarylheptanoids with anti-oxidative and anti-inflammatory activities. The crude extract and its phenolic diarylheptanoid were shown to have hepatoprotection in vitro. The present study investigated the active principles and their underlying mechanisms that provided protection against thioacetamide (TA)-induced hepatotoxicity in vivo. Hepatic injury was induced in adult male mice by a single injection of TA (50 mg/kg BW, i.p.). C. comosa ethanol extract (5-500 mg/kg BW, p.o.), isolated diarylheptanoids: (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, (D-049) or (3S)-1-(3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol, (D-092), (1-25 mg/kg BW, i.p.), was given prior to receiving TA. Changes in plasma activity of alanine transaminase (ALT), hepatic glutathione (GSH) content, the activities of superoxide dismutase (SOD) and catalase (CAT), and the expression levels of tumor necrosis factor (TNF-α) and cytochrome P450 2E1 (CYP 2E1) were determined at 24 h after TA-treatment. C. comosa extract suppressed the elevation of plasma ALT level in the TA-induced acute hepatotoxicity with increases in hepatic SOD and CAT activities. The protective effect was observed at 1 and 6 h prior to receiving TA and the effective dose was at 25 mg/kg BW. For pretreatment with diarylheptanoids, only non-phenolic diarylheptanoid, D-049 (5-25 mg/kg BW), provided the protection, but not phenolic diarylheptanoid, D-092. Moreover, D-049 suppressed the expression of pro-inflammatory cytokine TNF-α and CYP 2E1. These findings suggest that D-049 is an active principle in C. comosa that contributes hepatoprotection against TA-induced oxidative damage. It may mediate through its increased intracellular antioxidant enzymatic detoxification, which subsequently decrease the formation of bioactive metabolites of TA.
Journal of Ethnopharmacology, 2010
Aim of the study: To investigate the protective effect and possible mechanism of Curcuma comosa hexane extract on CCl 4 -induced liver injury in adult male mice. Materials and methods: Hepatotoxicity was induced by an intraperitoneal injection of CCl 4 and was evaluated after 24 h from the elevations of plasma alanine transaminase (ALT) and aspartate transaminase (AST) activities, and histological analysis of liver injuries. Hexane extract of Curcuma comosa was given at different time points from 1 to 72 h, prior to CCl 4 administration and the protection from liver injury was assessed. Results: CCl 4 -induced damage to liver cells was resulted in elevations of plasma ALT and AST activities. Pretreatment with Curcuma comosa hexane extract 24 h at a dose of 100, 250, and 500 mg/kg BW resulted in a dose-dependent prevention of the increases in plasma ALT and AST activities as well as time dependent. The protective effect of the extract at a dose of 500 mg/kg BW was seen at 12-24 h. Pretreatment of the extract completely prevented elevation of plasma ALT and AST activities, and centrilobular necrosis. The protective effect of Curcuma comosa was associated with restoration of hepatic glutathione content, and CYP2E1 catalytic activity, and its mRNA and protein levels as well as increase in activity of glutathione-S-transferase (GST). Conclusion: Curcuma comosa has a potent protective property against CCl 4 -induced hepatic injuries via the activation of detoxifying mechanisms (GST) as well as reduction of the bioactive toxic metabolites. Therefore, Curcuma comosa may be beneficial for prevention of hepatotoxicity.
Physiological changes due to hepatotoxicity and the protective role of some medicinal plants
Beni-Suef University Journal of Basic and Applied Sciences, 2016
The liver is the largest, important organ and the site for essential biochemical reactions in the human body. It has the function to detoxify toxic substances and synthesize useful biomolecules. Therefore, damage to the liver leads to grave consequences. This damage resulted from chronic alcoholic abuse, viral hepatitis or inherited metabolic disease. Liver damage is associated with cellular necrosis, fibrosis, and increase in tissue lipid peroxidation and depletion in tissue glutathione level. Most of the hepatotoxic chemicals damage liver cells mainly by inducing lipid peroxidation and other oxidative damages in the liver. Natural antioxidants are found in many compounds classified as secondary plant metabolites, e.g. polyphenols (phenolic acids and flavonoids) and terpenoids (carotenoids), and the consumption of foods that contain these compounds in large quantities seems to play an important role in prophylaxis against many diseases. Herbal medicines derived from plant extracts are being increasingly utilized to treat a wide variety of clinical disease. More attention has been paid to the protective effects of natural antioxidants against drug induced toxicities especially whenever free radical generation is involved. Popularity of herbal remedies is increasing and at least one quarter of patients with liver disease use botanicals. The World Health Organization (WHO) estimates that 80 percent of the population of some Asian and African countries presently use herbal medicine for some aspect of primary health care. Some medicinal herbs have proven hepatoprotective potential. Silybum marianum (milk thistle) has been used to treat liver diseases since the 16th century. Its major constituents are the flavonoids silibinin, silydianin, silychristin, and isosilibinin, of which silibinin is the biologically most active compound and used for standardization of pharmaceutical products.
Toxicology in Vitro, 2008
Syzygium cumini, Indian black plum or Java plum, is a rich source for anthocyanins (230 mg/100 g DW) showing high antioxidant activity in vitro. In the following study it is further demonstrated that S. cumini peel extract rich in anthocyanins (SCA) offers considerable protection against carbon tetrachloride (CCl 4)induced damage in rat hepatocytes. SCA itself being non-toxic to primary rat hepatocytes at concentrations ranging from 50 to 500 ppm, was found to suppress CCl 4-induced LDH leakage by 54% at 50 ppm, thereby improving the cell viability by 39%. The SCA significantly reversed the CCl 4 induced changes in cellular glutathione (GSH) level, lipid peroxidation and activity of the antioxidant enzyme glutathione peroxidase. Exposure of hepatocytes to SCA after CCl 4 treatment was found to elevate GSH and GPx activities by 2-folds, whereas the activities of catalase and superoxide dismutase were not significantly affected. The fruit pulp extract (SPE) was less effective in offering protection to rat hepatocytes, particularly in terms of total GSH content and a consequent increase in lipid peroxidation although the higher GPx activity suggests the probable involvement of GSH as a substrate for GPx. These observations suggest that the fruit peel extract of S. cumini, is largely responsible for the reversal of CCl 4-induced oxidative damage in rat hepatocytes. Both peel and pulp extract appear to offer protection to rat hepatocytes through GPx along with other biological pathways independent of catalase and superoxide dismutase.
Effects of few Indian medicinal herbs on carbon tetrachloride induced hepatic injury in animals
2009
The Phyllantus nirruri (PN), Andrographis paniculata (AP) and Picrroriza kurroa (PK) have been widely used in number of hepatoprotective formulations based on their traditional claims. However, no published data showing the comparative study of these herbs is available. The aim of the present study was to evaluate the hepatoprotective effect of standardised herbal extracts of PN 142.5 mg/kg, p.o), AP (300 mg/kg, p.o) and PK (200 mg/kg, p.o) on carbon tetrachloride (CCI 4) induced acute and chronic hepatic damage in rats. In chronic hepatitis, CCI 4 (0.2 ml/kg, p.o) was administered twice weekly during eight weeks of extract treatment, whereas, in acute hepatitis, CCI 4 (0.5 ml/kg, p.o) was given on 10 th day of administration of extract. Liver injury was analyzed by estimating the biochemical marker enzymes levels and antioxidant activities. Histological studies were also carried out. Statistically significant reversal of the elevated serum levels and depleted tissue levels of biochemical marker enzymes were found as the biochemical indices for hepatoprotection. The histological scores and liver weight was significantly reduced as well as SOD and catalase activities were significantly increased in treated groups compared to CCI 4 control. Further, PK and PN were found to be most and least effective respectively in chronic CCI 4 induced liver damage, whereas, AP exhibited least protection than PN and PK in acute CCI 4 hepatic injury. These results show that the standardised extracts PN, AP and PK possess hepatoprotective potential and prevented hepatic damage induced by CCI 4 .
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, 2010
This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl 4)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100 mg/kg of CLE or 100 mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl 4 administration. In addition, the CLE control group was pretreated with 100 mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl 4 (20 mg/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 CCl 4-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 CCl 4-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 CCl 4-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 CCl 4-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.
Antioxidant Property of Plant an Indication for Hepatoprotective Activity
2012
Liver, the largest organ in the body is being evolv ed to maintain the body’s internal milieu and also pro tect itself from the challenges it faces during its functioning. Since it is involved in the biochemical conversio ns of various endogenous and exogenously administered/ingested substances, there is a possibility of generation of various highly reactive species of fr ee radicals. However, it has an inbuilt system like tissue glutathione (GSH), etc to scavenge them off . Inspite of this the free radicals generated by some hepatotoxins like CCl4 may overpower the protective mechanism of the live r and cause hepatic damage. Though the modern medicinal system has grown phenomenally, the drug f or treating hepatic disease is still a dream. Hence , people are looking at the traditional systems of me dicine for remedies to hepatic disorders.
TheScientificWorldJournal, 2014
Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of medicine to treat several diseases such as hepatitis, liver complaints, and diabetes. It has been consumed as food supplement and "jamu" as a remedy for hepatitis. Hence, CX was further explored for its potential as a functional food for liver related diseases. As such, initiative was taken to evaluate the antioxidant and hepatoprotective potential of CX rhizome. Antioxidant activity of the standardized CX fractions was determined using in vitro assays. Hepatoprotective assay was conducted against carbon tetrachloride- (CCl4-) induced hepatic damage in rats at doses of 125, 250, and 500 mg/kg of hexane fraction. Highest antioxidant activity was found in hexane fraction. In the case of hepatoprotective activity, CX hexane fraction showed significant improvement in terms of a biochemical liver function, antioxidative liver enzymes, and lipid peroxidation activity. Good recovery was observed in the...
Hepatoprotective efficacy of ethanolic extracts of rhizome Curcuma amada Roxb. In experimental rats
Thescope of this study is to evaluate the hepatoprotective efficacy of rhizome Curcuma Amada Roxb (CAR) in CCl4 induced hepatotoxicity in rats. Male Albino Wister rats were divided into six groups (n=6). Group I served as the normal control group and received olive oil (i.p. 0.5 mL/kg b.w.) as a vehicle. Group II served as high dose group and received 400mg/kg b.w CAR. Group III served as the carbon tetrachloride (CCl4) group and received CCl4 (i.p., 0.1 mL/kg b.w., 50% CCl4 in olive oil). Groups IV–VI served as the treatment groups, and they received CARdissolved in distilled water orally at dose levels of 100, 200, and 400 mg/kg b.w., respectively, with CCl4 (i.p., 0.1 mL/kg b.w., 50% CCl4 in olive oil). All the groups were given the respective dosages twice a week for 28 days. The result of the marker enzymes AST, ALT, ALP and TBARS in the serum sample revealed an appreciable increase in groups IV, V and VI with respect to CCl4 treated group. This confirmed the hepatoprotective nature of CAR there by deactivating the phase II detoxifying enzymes, preventing the formation of free radical and protecting the cell membrane from degeneration. The nonenzymatic antioxidants pattern of GSH, GPX and GST showed decreased levels with respect to group III. This confirmed that CAR has induced the GSH antioxidant system by increasing cellular defense against reactive free radicals and other oxidative species. The histological architecture of liver sections in Group-IV–VI showed more or less normal lobular pattern with mild degrees of fatty change, necrosis and lymphocyte infiltration almost comparable to those of control group. These results act as a supporting evidence to exhibit the hepatoprotective nature of CAR.
Objective: To investigated the hematological, antioxidant and protective performance of Usnea longissima (U. longissima) on CCl4 induced hepatotoxicity in experimental animals. Methods: Hepatotoxicity was induced by CCl4 (1 mL/kg body weigt 1:1 CCl4 i.p.), ethanolic U. longissima extracts at a doses (200 and 400 mg/kg body weigt) were administered to and compared with Silymarin (25 mg/kg body weigt) and hematological, antioxidant and enzymatic, non-enzymatic parameters were assessed through the liver functions test. All the observation was also supplemented with histopathological examination of liver sections. Results: Phytochemical investigation showed that ethanolic extract contains poly phenolic compounds tannins, flavonoids, alkaloids and saponins and acute toxicity study shows that ethanolic extract was safe up to 2 000 mg/kg body weight. The toxicant induced a rise in the plasma enzyme levels of ALT, AST, ALP and total bilirubin level. This increased level was significantly decreased by the extract at 400 mg/kg body weight than 200 mg/kg body weight. The animals were prevented (partly or fully) which was showed in the histopathological changes using ethonolic U. longissima extract. Conclusions: The outcome of this study reveals that, there is a powerful antioxidant and hepatoprotective activity of U. longissima. It is believed that the present constituents are responsible for courting the hepatic disease and alternative components have the power to act as free radical scavenging properties.