P. K. S. Visen

Ursolic acid isolated from Eucalyptus tereticornis protects against ethanol toxicity in isolated rat hepatocytes

Ursolic acid is the active material isolated from the leaves of the Eucalyptus hybrid E. tereticornis. In the present study, it has shown a significant preventive effect in vitro against ethanol‐induced toxicity in isolated rat hepatocytes. Compared with the incubation of isolated hepatocytes with ethanol only, the simultaneous presence of ursolic acid in the cell suspension preserved the viability of hepatocytes and reversed the ethanol‐induced loss in the level of all the marker enzymes (AST, ALT and AP) studied. Ethanol alone resulted in a 48%–54% decrease in the viability and a 42%–54% reduction in the biochemical parameters of the hepatocytes. Ursolic acid showed a concentration dependent (1–100 µg/mL) preventive effect (12%–76%) on alcohol‐induced hepatocyte toxicity by restoring the altered parameters. The results thus suggest the effective use of an in vitro test system as an alternative for in vivo assessment of hepatoprotective activity of purified material. Copyright

Ex vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats

Picroliv, the active constituent isolated from the plant Picrorhiza kurroa, was evaluated as a hepatoprotective agent against ethanol-induced hepatic injury in rats. Alcohol feeding (3.75 g/kg x45 days) produced 20-114% alteration in selected serum (AST, ALT and ALP) and liver markers (lipid, glycogen and protein). Further, it reduced the viability (44-48%) of isolated hepatocytes (ex vivo) as assessed by Trypan blue exclusion and rate of oxygen uptake. Its effect was also seen on specific alcohol-metabolizing enzymes (aldehyde dehydrogenase, 41%; acetaldehyde dehydrogenase, 52%) in rat hepatocytes. The levels of these enzymes were found to be reduced in the cells following alcohol intoxication. Ethyl alcohol also produced cholestasis (41-53%), as indicated by reduction in bile volume, bile salts and bile acids. Picroliv treatment (3-12 mg/kg p.o. x45 days) restored the altered parameters in a dose-dependent manner (36-100%).

Curative effect of picroliv on primary cultured rat hepatocytes against different hepatotoxins: an in vitro study

Picroliv, the standardized active principle from the plant Picrorhiza kurrooa showed significant curative activity in vitro in primary cultured rat hepatocytes against toxicity induced by thioacetamide (200 microg/mL), galactosamine (400 microg/mL), and carbon tetrachloride (3 microl/mL). Activity was assessed by determining the change in hepatocyte viability and rate of oxygen uptake and other biochemical parameters (GOT, GPT, and AP). The toxic agents alone produced a 40-62% inhibition of cell viability and a reduction of biochemical parameters after 24 h of incubation at 37 degrees C which (on removal of the toxic agents) was reversed after further incubation for 48 h. Incubation of damaged hepatocytes with picroliv exhibited a concentration- (1-100 microg/mL) dependent curative effect in restoring altered viability parameters. The results warrant the use of this in vitro system as an alternative for in vivo assessment of hepatoprotective activity of new agents.

Hepatoprotective Activity of Ricinus communis Leaves

AbstractRicinus communis (leaf extract) was evaluated for hepatoprotective, choleretic and anticholestatic activity. In a preliminary test with albino rats, an ethanol extract showed significant protection against galactosamine-induced hepatic damage. It also showed dose-dependent choleretic and anti cholestatic activity, and hepatoprotective activity as judged by hepatocytes isolated from paraceta mol-treated rats. On fractionation of the ethanol extract, maximum activity was localised in the butanol fraction. Subsequent chromatographic fractionation and testing in the galactosamine model led to the isolation of two active fractions which in turn yielded two pure compounds: ricinine and N-demethyl-ricinine. N-Demethyl-ricinine was found to be more active and it reversed the biochemical changes produced by galactosamine at a dose of 6 mg/kg x 7 days. It possessed marked choleretic activity and demonstrated an anticholestatic effect against paracetamol-induced cholestasis.

Prevention of galactosamine - induced hepatic damage by the natural product loganin from the plant Strychnos nux-vomica : Studies on isolated hepatocytes and bile flow in rat

Loganin an iridoid glycoside extracted from the fruit of the plant, Strychnos nux‐vomica, in an earlier study showed hepatoprotection in primary screening. The present detailed study has been carried out in isolated hepatocytes (ex vivo) and on bile flow (in vivo) against galactosamine induced hepatic damage in rats to determine its pharmacological potential. Loganin was given to rats at preselected doses (3, 6 and 12 mg/kg p.o. ×7). Silymarin a standard compound was given at the same doses for comparison. On day 7 galactosamine (400 mg/kg) was injected intraperitoneally. Study on isolated hepatocytes and bile flow was carried out 24 h after treatment with galactosamine. Isolation of rat hepatocytes and collection of bile were done according to standard methods. Galactosamine reduced the viability of hepatocytes as well as bile volume and bile contents. Loganin showed a dose dependent activity (14%–67%) as observed by an increase in the viability of hepatocytes and the reversal of reduced parameters of bile. The activity of silymarin a known compound was found comparable. Loganin showed significant hepatoprotective and anticholestatic activities and confirms the earlier findings. The present study warrants detailed pharmacological evaluation.

Effect of Andrographolide on Monkey Hepatocytes against Galactosamine Induced Cell Toxicity : An In-Vitro Study

Andrographolide, the active constituent, isolated from the plant Andrographis paniculata showed concentration dependent (1-100 microg/mL) activity against galactosamine (GALN 400 microg/mL) induced acute injury in isolated monkey hepatocytes, following 48 hours of the incubation at 370 C. The effect of andrographolide was measured on viability (trypan blue exclusion and oxygen uptake tests), biochemical marker enzymes - aspartate amino transaminase (AST), alanine amino transaminase (ALT) and alkaline phosphatase (AlP) and bile contents (bile salts and bile acids). It significantly increased the percent viability of cells and was capable of preserving 90-100% cell integrity. The cellular leakage of enzymes and bile contents following incubation with GALN was significantly modulated by andrographolide treatment. Its activity was found superior to that of silymarin, a standard hepatoprotective compound, tested simultaneously for comparison. The findings also emphasize the possible use of an in-vitro primary cell culture system as an alternative to in-vivo, in the early stage of drug discovery.

Hepatoprotective effect of picroliv against rifampicin-induced toxicity

Picroliv, the active constituent of the plant Picrorhiza Kurroa, showed significant hepatoprotective as well as anticholestatic activity against rifampicin‐induced hepatic damage. Rifampicin (50 mg/kg ip × 6 days) resulted in the reduction of bile flow as well as its contents (bile salts and bile acids) in the conscious rat and anesthetized guinea pig. Further, it also caused a decrease in the viability and rate of oxygen consumption in isolated rat hepatocytes. Picroliv treatment significantly reversed the altered parameters of bile and hepatocytes. The hepatoprotective drug silymarin on comparison was found to be less active than picroliv. Drug Dev. Res. 40:299–303, 1997.