ABSTRACT
Yahom Ampanthong, a Thai traditional medicine, is commonly used for treatment of nausea, vomiting and syncope. Its formula is composed of more than 10 medicinal plants. Currently, the herbal-drug interactions were reported among the case of co-administration of traditional and Western medicines, since cytochrome P450 enzymes involve in drug metabolism and affect the drug action. This study aimed to investigate the effects of Yahom extracts on hepatic cytochrome P450 enzymes and pentobarbital-induced sleeping in mice. Powder of Yahom Ampanthong was extracted with three different solvents, i.e., dichloromethane, methanol and distilled water. The activities of CYP1A1, CYP1A2, CYP2B, CYP2E1 and CYP3A4 were determined after the administration of Yahom extracts for 4 weeks. All three extracts significantly inhibited CYP1A1, CYP1A2, CYP2E1 activities. In contrast, only dichloromethane and methanol extracts enhanced CYP2B activity. However, all three extracts did not affect CYP3A4 activity. When compared to the control group, the dichloromethane extract-treated animals showed shorter pentobarbital-induced sleeping time after treatment for 1 and 4 weeks. In conclusion, Yahom Ampanthong extracts modulated hepatic microsomal cytochrome P450 activities and decreased the pentobarbital-induced sleeping time. Therefore, the concomitant administration of Yahom with certain drugs may give rise to the herbal-drug interaction, which may affect the clinical implication of drug actions.
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Liver/enzymology , Medicine, Traditional/methods , Pentobarbital/pharmacology , Animals , Drug Interactions , Isoenzymes/chemistry , Male , Methylene Chloride/pharmacology , Mice , Mice, Inbred ICR , Microsomes/drug effects , Powders , Sleep/drug effects , Solvents/chemistryABSTRACT
The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, beta-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 or AhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A. paniculata, according to its ability to induce CYP1A1 expression.
Subject(s)
Andrographis/chemistry , Cytochrome P-450 CYP1A1/drug effects , Diterpenes/pharmacology , Gene Expression Regulation/drug effects , Animals , Benz(a)Anthracenes/administration & dosage , Benz(a)Anthracenes/pharmacology , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 Enzyme System/biosynthesis , Cytochrome P-450 Enzyme System/drug effects , Diterpenes/administration & dosage , Dose-Response Relationship, Drug , Drug Synergism , Enzyme Induction , Hepatocytes/enzymology , Male , Mice , Polychlorinated Dibenzodioxins/administration & dosage , Polychlorinated Dibenzodioxins/pharmacology , Receptors, Aryl Hydrocarbon/drug effects , Receptors, Aryl Hydrocarbon/metabolism , Resveratrol , Stilbenes/pharmacology , beta-Naphthoflavone/administration & dosage , beta-Naphthoflavone/pharmacologyABSTRACT
Three antioxidant vitamins, the alpha- and beta-carotenes as well as vitamin E, were measured in sera of a normal population in Northeastern Thailand using HPLC. The mean serum beta-carotene level of females was significantly higher than the value for males, i.e, 37.55 (95%CI=34.59-40.51) versus 32.97 (95% CI=30.01-35.93) micro/dl. The beta-carotene level tended to decrease as age increased, particularly in the male population. The mean serum beta-carotene level was also higher in females than in males, i.e., 7.08 (95%CI=6.57-7.59) and 6.26 (95% CI=5.77-6.75) micro/dl, respectively. The average serum alpha-tocopherol (Vitamin E) level of the whole population was 1.08 (95% CI=1.04-1.12) micro/dl and did not show age or sex differences. In general, the serum antioxidant vitamins of smokers were lower than those of the non-smokers but a significant difference was observed only for alpha-tocopherol. Alcohol drinking resulted in slightly lower serum beta-carotene values, whereas coffee or tea drinking and betel nut chewing did not cause any differences with these three antioxidant vitamins. However, we report higher in serum beta-carotene levels of people in Ban Fang district than in Chonnabot district. The results from our study give the base line data of serum antioxidant vitamins in a Thai population and also suggest future intensive study on the relationship of dietary intake and cancer prevention.
