The effects of Urtica dioica L. leaf extract on aniline 4-hydroxylase in mice.

The effects of hydroalcoholic (80% ethanol-20% water) extract of Urtica dioica L. on microsomal aniline 4-hydroxylase (A4H) were investigated in the liver of Swiss albino mice (8- 10-weeks-old) treated with two doses (50 and 100 mg/kg body weight, given orally for 14 days ). The activities of A4H showed a significant increase in the liver at both dose levels of extract treatment. The hydroalcoholic extract of Urtica dioica induced the activities of A4H that had been increased by treatment of metal ions (Mg2+ and Ca2+) and the mixture of cofactors (NADH and NADPH). At saturated concentration of cofactor, microsomal A4H exhibited significantly even higher activities in the presence of the mixture of cofactors than NADPH and NADH. Mg2+ and Ca2+ ions acted as stimulants in vitro. The present results suggest that the hydroalcoholic extract of Urtica dioica may have modalatory effect on aniline hydroxylase at least in part and enhance the activity of A4H adding metals ions and cofactors.

Anti-hepatotoxic effects of Rosa rugosa root and its compound, rosamultin, in rats intoxicated with bromobenzene.

The effects of a methanol extract of Rosa rugosa root and its triterpenoid glycoside, rosamultin, on hepatic lipid peroxidation and drug-metabolizing enzymes were investigated in rats treated with bromobenzene. The methanol extract of R. rugosa root reduced the activities of aminopyrine N-demethylase and aniline hydroxylase, which had been increased by bromobenzene, but rosamultin did not affect the activities of the two enzymes. Both the methanol extract and rosamultin restored the activity of epoxide hydrolase, which had also been decreased by bromobenzene. Hepatic glutathione concentrations were lowered and hepatic lipid peroxides were increased in rats intoxicated with bromobenzene. The hepatic lipid peroxidation induced by bromobenzene was prevented with the methanol extract and rosamultin. However, the decrease in glutathione was not altered by the methanol extract of R. rugosa. These results suggest that the extract of R. rugosa and its compound, rosamultin, may protect against bromobenzene-induced hepatotoxicity through, at least in part, enhanced activity of epoxide hydrolase. Antioxidant properties may contribute to the protection of R. rugosa against bromobenzene-induced hepatotoxicity.

Protection by Osbeckia aspera against carbon tetrachloride-mediated alterations in microsomal drug metabolizing enzyme activity.

Previous investigations have confirmed the protective effect of Osbeckia aspera leaf extract on carbon tetrachloride-mediated liver injury in rat models. It is well known that the earliest alterations in liver cell structure and function following carbon tetrachloride poisoning involve the endoplasmic reticulum and its drug metabolizing enzymes. Therefore, we investigated whether an aqueous leaf extract of O. aspera could offer protection against carbon tetrachloride-induced changes in the microsomal drug metabolizing enzymes aniline hydroxylase and p-aminopyrine N-demethylase. This enzyme activity was compared with phenobarbital-induced righting reflex and lipid peroxidation. Treatment of rats with the aqueous leaf extract of O. aspera (before or after the administration of carbon tetrachloride) resulted in a marked decrease in carbon tetrachloride-mediated alterations in aniline hydroxylase and p-aminopyrine N-demethylase activity, phenobarbital-induced loss of righting reflex and malondialdehyde formation due to lipid peroxidation. The Km value of these enzymes in control and Osbeckia-treated rats were the same. These results show that the plant extract can markedly decrease the carbon tetrachloride-mediated reduction in aniline hydroxylase and p-aminopyrine N-demethylase activity and inhibit peroxidative damage to the cell membrane. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies suggested that the effects of the plant extract was neither due to an induction of the drug-metabolizing enzymes under investigation, nor due to an alteration in the Km values of these enzymes.

Free-radical scavenging action of medicinal herbs from Ghana: Thonningia sanguinea on experimentally-induced liver injuries.

The antioxidant action of medicinal herbs used in Ghana for treating various ailments was evaluated in vitro and in vivo. Five plants, Desmodium adscendens, Indigofera arrecta, Trema occidentalis, Caparis erythrocarpus, and Thonningia sanguinea were tested for their free radical scavenging action by their interaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH). Of these five plants, only Thonningia sanguinea was found to scavenge the DPPH radical. Lipid peroxidation in liver microsomes induced by H2O2 was also inhibited by T. sanguinea. The hepatoprotective effect of T. sanguinea was studied on acute hepatitis induced in rats by a single dose of galactosamine (GalN, 400 mg/kg, IP) and in mice by carbon tetrachloride (CCl4, 25 microl/kg, IP). GalN induced hepatotoxicity in rats as evidenced by an increase in alanine aminotransferase (ALT) and glutathione (GSH) S-transferase activities in serum was significantly inhibited when T. sanguinea extract (5 ml/kg, IP) was given to rats 12 hr and 1 hr before GalN treatment. The activity of liver microsomal GSH S-transferase, which is known to be activated by oxidative stress, was increased by the GaIN treatment and this increase was blocked by T. sanguinea pretreatment. Similarly, T. sanguinea pretreatment also inhibited CCl4-induced hepatotoxicity in mice. These data indicate that T. sanguinea is a potent antioxidant and can offer protection against GalN- or CCl4-induced hepatotoxicity.

[Effects of sino-Japanese herbs in the family Compositae on the hepatic drug metabolizing enzymes and lipid peroxidation in rats].

The effects of hot water extracts (HWEs) from 15 kinds of Compositae herbs and distanninized fractions (DTFs) from 9 of these herbs on rat hepatic lipid peroxidation (LPO) and the activities of aminopyrine N-demethylase (APD) and aniline hydroxylase (ANH) were examined in vitro. The APD activity was inhibited by HWEs from 12 herbs, of which the effect of HWE from Inchinko was remarkable. Inhibitory effects of DTFs from Inchinko, Gaiyo, Kantoka, Sojustu and Byakujutsu on the APD activity were smaller, if any, than those of the corresponding HWEs, whereas DTF from Koka enhanced the activity of APD. The ANH activity was inhibited by HWEs from 11 herbs. HWEs from Inchinko, Gaiyo and Senpukuka increased the ANH activity, whereas the DTFs from them caused inhibition. The inhibitory effect of DTF from Shion on the ANH activity was smaller than that of the corresponding HWE, but the effects of DTFs from Koka, Byakujutsu, Sojutsu and Mokko were larger than those of the respective HWEs. LPO was inhibited by HWEs from 14 herbs, of which the HWEs from Inchinko, Gaiyo, Kantoka, Koka and Mokko caused marked inhibitions. Except in the case of Shion, the inhibitory effects of DTFs on LPO were smaller than those of the corresponding HWEs, whereas DTF from Koka still showed a marked inhibition. In the present experiments, it is suggested that Inchinko, Gaiyo, Koka, Kikuka, Senpukuka, Byakujutsu, Sojutsu and Mokko, which showed remarkable effects on LPO and the activities of APD and ANH, might also exert their effects in vivo.