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 microg/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.

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%).

Picroliv prevents oxidation in serum lipoprotein lipids of Mastomys coucha infected with Plasmodium berghei.

Picroliv, an iridoid glycoside mixture from the root and rhizome of Picrorhiza kurrooa, at the dose of 6 mg/kg p.o. for two weeks provided significant protection against the generation of lipid peroxidation products in serum beta-lipoproteins of P. berghei infected M. coucha. Incubation of normal rat hepatocytes with very low density lipoprotein or low density lipoprotein isolated from infected animals caused significant generation of lipid peroxides followed by a decrease in the viability of these cells, however these effects were partially reversed with the lipoproteins from infected and picroliv treated groups. High density lipoprotein from infected animals was not toxic to hepatocytes in vitro.

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.

Protective effect of picroliv, active constituent of Picrorhiza kurrooa, against oxytetracycline induced hepatic damage.

Picroliv, the active constituent of P. kurrooa, showed a dose dependent (1.5-12 mg/kg, po for 7 days) hepatoprotective activity against oxytetracycline induced hepatic damage in rat. It increased the number of viable hepatocytes (ex-vivo) significantly. Increase in bile volume and its contents in conscious rat suggests potent anticholestatic property. Picroliv also antagonised alterations in enzyme levels (GOT, GPT, and alkaline phosphatase) in isolated hepatocytes and serum, induced by oxytetracycline (200 mg/kg, i.p.) feeding. Picroliv was more potent than silymarin a known hepatoprotective drug.

Andrographolide protects rat hepatocytes against paracetamol-induced damage.

Andrographolide, the active constituent isolated from the plant Andrographis paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o. x 7) protective activity against paracetamol-induced toxicity on ex vivo preparation of isolated rat hepatocytes. It significantly increased the percent viability of the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It completely antagonized the toxic effects of paracetamol on certain enzymes (GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. Andrographolide was found to be more potent than silymarin, a standard hepatoprotective agent.

Anticholestatic effect of picroliv, active hepatoprotective principle of Picrorhiza kurrooa, against carbon tetrachloride induced cholestasis.

Picroliv showed a dose (3-12 mg/kg, po for 7 days) dependent choleretic activity as evidenced by increase in bile flow and its contents (bile salts and bile acids). Significant anticholestatic activity was also observed against carbon tetrachloride induced cholestasis in conscious rat, anaesthetized guinea pig and cat. Picroliv was more active than the known hepatoprotective drug silymarin.

Prevention of galactosamine-induced hepatic damage by picroliv: study on bile flow and isolated hepatocytes (ex vivo).

Picroliv, a standardized extract from the plant Picrorhiza kurrooa containing active constituents, showed a significant dose dependent (3-12 mg/kg p.o. x 7) protective activity against galactosamine-induced hepatic damage in rat as evaluated on the isolated hepatocytes (ex vivo) preparation. It markedly increased the percentage of viability of hepatocytes. It also restored the galactosamine-induced changes in the levels of enzymes (GOT, GPT and alkaline phosphatase) both in isolated hepatic cells as well as in serum. In addition, picroliv possessed a marked anticholestatic effect. Picroliv was found to be more potent than silymarin, a standard hepatoprotective agent.

Effect of picroliv on low density lipoprotein receptor binding of rat hepatocytes in hepatic damage induced by paracetamol.

Picroliv from root and rhizome of Picrorhiza kurroa showed reversal of low density lipoprotein (LDL) binding to paracetamol-induced damaged hepatocytes of rats. Changes in levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, conjugated dienes and lipids of hepatocytes were significantly prevented by picroliv at different doses. The effect of picroliv on enzyme levels, LDL receptor binding and lipids in damaged hepatocytes was found to be comparable to silymarin, a known hepatoprotective agent.

Choleretic effect of andrographolide in rats and guinea pigs.

Andrographolide from the herb Andrographis paniculata (whole plant) per se produces a significant dose (1.5-12 mg/kg) dependent choleretic effect (4.8-73%) as evidenced by increase in bile flow, bile salt, and bile acids in conscious rats and anaesthetized guinea pigs. The paracetamol induced decrease in volume and contents of bile was prevented significantly by andrographolide pretreatment. It was found to be more potent than silymarin, a clinically used hepatoprotective agent.

Choleretic effect of picroliv, the hepatoprotective principle of Picrorhiza kurroa.

Picroliv, the hepatoprotective principle of the plant Picrorhiza kurroa, showed a dose-dependent (1.5-12 mg/kg x 7) choleretic effect in conscious rats and anaesthetised guinea pigs. It also possessed a marked anticholestatic effect against paracetamol- and ethynylestradiol-induced cholestasis. It antagonised the changes in bile volume as well as the contents (bile salts and bile acids). Silymarin, a known hepatoprotective agent, was tested simultaneously for comparison. Picroliv was found to be a more potent choleretic and anticholestatic agent than silymarin.

Synthesis and anthelmintic activity of 2,2'-disubstituted 5,5'-dibenzimidazolylsulfides and sulfones.

A number of substituted diphenylsulfides and sulfones (4-11) and 2,2'-disubstituted-5,5'-dibenzimidazolyl sulfides and sulphones (12-19) have been synthesized starting from 5-chloro-2-nitroacetanilide and (3) 4,4'-dichlorodiphenyl sulfone (9), respectively. Among the compounds tested against Ancylostoma ceylanicum in hamsters and Hymenolepis nana in rats and mice, 14, 15, 18 and 19 removed 100% of the worms at an oral dose of 25 mg/kg X 1 to 250 mg/kg X 3. Some of the compounds were tested for their blood schizontocidal activity against Plasmodium berghei in mice but none showed any activity up to an oral dose of 10 mg/kg given for 6 days.

Comparative efficacy of standard antihookworm drugs against various test nematodes.

The chemotherapeutic responses of three test nematodes, Nippostrongylus brasiliensis, Nematospiroides dubius and Ancylostoma ceylanicum to standard antihookworm drugs were assessed in order to select a suitable host-parasite system for the primary screening of potential antihookworm compounds. N. dubius behaved inconsistently and, with some infections, required more drug to achieve 100% clearance. Nippostrongylus brasiliensis was found to be sensitive to thiabendazole, tetramisole and levamisole but the broad spectrum anthelmintic mebendazole was ineffective. A. ceylanicum was very sensitive to mebendazole, sensitive to tetramisole and levamisole and refractory to thiabendazole. In vitro, none of the compounds had any lethal effect against any of the nematodes, except mebendazole against A. ceylanicum. A. ceylanicum does occur in man and its chemotherapeutic reactions are similar to those of target hookworm infections of economic importance. As such, although not equally sensitive to standard anthelmintics, it is recommended for routine primary screening.