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.

High density lipoprotein subclasses inhibit low density lipoprotein oxidation.

It has been reported earlier that high density lipoprotein (HDL) is a scavenger of superoxide anions, hydroxyl radicals (OH-) and behaves like superoxide dismutase. In the present investigation, we have studied the effect of HDL subclasses: HDL2 and HDL3 on non enzymatically induced oxidation of low density lipoprotein (LDL) by Fe2+ and sodium ascorbate. Both HDL2 and HDL3 showed protection against the oxidative degradation of LDL-lipids, measured as thiobarbituric acid reactive substance, lipid hydroperoxide and conjugated diene. Oxidized LDL was more electronegative, as evidenced by the increase in relative electrophoretic mobility(REM) on agarose gel. HDL3 significantly protected LDL apoprotein as assessed by reversal of REM after oxidation. HDL2 and HDL3 significantly inhibited the generation of OH- in nonenzymic systems in vitro. However, HDL2 was more active against enzymic formation of OH- as compared to HDL3. Alpha-tocopherol could protect LDL lipids and apoprotein components by Fe2+ mediated oxidation but the effects were lower than HDL subclasses. Our findings suggest that HDL subclasses, the potent scavenger of oxygen derived free radicals, play an important role to prevent the oxidative modifications in LDL.

Picroliv affects gamma-glutamyl cycle in liver and brain of Mastomys natalensis infected with Plasmodium berghei.

Picroliv, the standardized preparation of iridoid glycosides from Picrorhiza kurrooa, at the dose of 6 mg/kg, po for two weeks provided significant protection against depletion of reduced glutathione levels in liver and brain of Plasmodium berghei infected Mastomys natalensis. The activation of gamma-glutamyl transpeptidase enzyme and decreased levels of cysteine, sulphydryl groups as well as glutathione synthesis in both tissues due to P. berghei infection were reversed by picroliv. Enzymatic and non enzymatic lipid peroxidation in microsomes in vitro was significantly reduced by picroliv along with the recovery of reduced glutathione.

Role of free radicals in Plasmodium berghei infected Mastomys natalensis brain.

Lipid peroxide, lipid hydroperoxide, reduced glutathione, oxidised glutathione, lipofuscin contents and the activity of the enzyme superoxide dismutase were assessed in P. berghei infected M. natalensis brain. The results showed significant increase in the levels of lipid peroxides, lipid hydroperoxides and lipofuscin in brain subcellular fractions of P. berghei infected M. natalensis. Furthermore, a depressed superoxide dismutase activity was observed along with regulation in glutathione content. An elevated level of lipid peroxidation products along with depressed activity of scavengers in brain during malaria highlights the role of free radicals in malarial pathology.

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.

Effect of picroliv on glutathione metabolism in liver and brain of Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, the active principle from Picrorhiza kurrooa, at a dose of 6 mg/kg, po for two weeks showed significant protection against changes in liver and brain glutathione metabolism of Plasmodium berghei infected Mastomys natalensis. The depletion of reduced glutathione level and inhibition of glutathione-S-transferase, glutathione reductase and glutathione peroxidase activities due to P. berghei infection were markedly recovered by picroliv. The increased levels of lipid peroxidation products in damaged tissues were also reduced along with the recovery of glutathione metabolism.

Hypolipidemic activity of Achyranthus aspera Linn in normal and triton induced hyperlipemic rats.

The alcoholic extract of A. aspera, at 100 mg/kg dose lowered serum cholesterol (TC), phospholipid (PL). triglyceride (TG) and total lipids (TL) levels by 60, 51, 33 and 53% respectively in triton induced hyperlipidemic rats. The chronic administration of this drug at the same doses to normal rats for 30 days, lowered serum TC, PL, TG and TL by 56, 62, 68 and 67% respectively followed by significant reduction in the levels of hepatic lipids. The faecal excretion of cholic acid and deoxycholic acid increased by 24 and 40% respectively under the action of this drug. The possible mechanism of action of cholesterol lowering activity of A. aspera may be due to rapid excretion of bile acids causing low absorption of cholesterol.

Effect of picroliv on protein and nucleic acid synthesis.

Oral administration of picroliv, a standardised fraction of roots and rhizomes of Picrorhiza kurroa, showed stimulation of nucleic acid and protein synthesis in rat liver. Results are comparable with a standard hepatoprotective agent, silymarin.

Protective effect of coleonol on biochemical changes produced in coronary ligation induced ischemia.

Coleonol, a diterpine prevented biochemical changes induced by coronary artery ligation in rabbits at a dose of 10 mg/kg, iv. It increased the heart mitochondrial oxygen uptake and O ratio, which may be responsible for the stabilization of heart membrane. The decrease in serum creatine phosphokinase, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase phospholipase and lipid peroxide and increase in cytochrome P450, glycogen and superoxide dismutase activity by coleonol treatment could have contributed to restore myocardial integrity and cardiac function disturbed by coronary artery ligation. The cardioprotective activity of coleonol was found to be comparable to propranolol.

Hepatoprotective activity of picroliv against carbon tetrachloride-induced liver damage in rats.

Administration of carbon tetrachloride to normal rats increased activities of hepatic 5(1)-nucleotidase, acid phosphatase, acid ribonuclease while the activities of succinate dehydrogenase, glucose 6-phosphatase, superoxide dismutase and cytochrome P450 were decreased. Levels of lipid peroxides, total lipids and cholesterol of liver were also increased. The activities of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase were increased. Other serum parameters showing changes after carbon tetrachloride were: bilirubin, proteins, cholesterol, triglycerides and lipoprotein-X. Picroliv (from the plant Picrorhiza kurroa) in doses of 6 and 12 mg/kg provided a significant protection against most of the biochemical alterations produced by carbon tetrachloride. The degree of protection afforded by picroliv, when administered simultaneously or as a pretreatment was almost equal.

Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, a standardized fraction of alcoholic extent of Picrorhiza kurroa (3-12 mg/kg/day for two weeks) simultaneously with P. berghei infection showed significant protection against hepatic damage in Mastomys natalensis. The increased levels of serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase, lipoprotein-X (LP-X) and bilirubin in the infected animals were marked reduced by different doses of picroliv. In the liver, picroliv decreased the levels of lipid peroxides and hydroperoxides and facilitated the recovery of superoxide dismutase and glycogen. Picroliv had no effect on the degree of parasitaemia.

Hepatic low density lipoprotein receptor binding and lipid profile in Mastomys natalensis during Plasmodium berghei infection.

Plasmodium berghei infection to Mastomys natalensis showed hyper beta-lipoproteinemia. The increase in serum cholesterol is associated with decreased uptake of low density lipoprotein (LDL) by the liver through receptor mediated endocytosis. The membranes prepared from infected M. natalensis exhibit up to 50% decline in high affinity binding sites for human 125I-LDL. Significant increases in serum lipids, cholesterol, triglyceride and lipid peroxide (LPO) contents of liver membrane were observed. Effects of lipid constituents and LPO content of liver membrane in relation to LDL catabolism and other possible mechanisms have been explained.

Hepatoprotective activity of silymarin against hepatic damage in Mastomys natalensis infected with Plasmodium berghei.

Silymarin, a flavolignan from the seeds of Silybum marianum, showed significant hepatoprotective activity in P. berghei-induced hepatic damage in M. natalensis, as assessed by changes in several serum and liver biochemical parameters. Changes in lipoprotein-X, GOT, GPT, alkaline phosphatase and bilirubin were found to be protected by silymarin at different doses. Maximum activity was observed at a dose of 5 mg/kg bw, po. Silymarin had no effect on parasitaemia.

Reversal of changes of lipid peroxide, xanthine oxidase and superoxide dismutase by cardio-protective drugs in isoproterenol induced myocardial necrosis in rats.

In myocardial necrosis produced by isoproterenol (beta-adrenergic agonist) marked increase in creatine phosphokinase, phospholipase and significant decrease in cardiac glycogen and phospholipid levels were observed. The enhanced levels of lipid peroxides, xanthine oxidase activity and lowering of superoxide dismutase may lead to excessive formation of free radicals resulting in cardiac cell damage. Nifedipine--a calcium antagonist, Propranolol--a beta-blocker and guggulsterone a lipid lowering agent showed marked reversal of these metabolic changes related to ischemia induced by isoproterenol.

Cardiac sarcolemma enzymes & liver microsomal cytochrome P450 in isoproterenol treated rats.

In the heart sarcolemma and sarcoplasmic reticulum of rat there was significant decrease in cholesterol and phospholipid levels in isoproterenol treated rats. The membrane enzymes lipoprotein lipase and Ca-ATPase decreased due to myocardial necrosis. Lipid peroxide and xanthine oxidase were significantly enhanced, whereas superoxide dismutase was markedly decreased in ischemic heart produced by isoproterenol. Cytochrome P450, b5 and heme were found to be degraded in myocardial cell damage. Guggulsterone showed a marked protective effect on the cardiac enzymes and cyt P450 system against myocardial necrosis induced by isoproterenol.