It has been demonstrated that L-pipecolic acid (L-PA), a major metabolic intermediate of L-lysine (L-Lys) in the mammalian and chicken brain, is involved in the functioning of the GABAergic system. A previous study has shown that intracerebroventricular (i.c.v.) injection of L-PA suppressed feeding and induced sleep-like behavior in neonatal chicks; however, the precise relationship between the GABAergic system and L-PA has not been clarified. In the present study, the role of the GABA-A or GABA-B receptors in the suppression of food intake and induction of sleeping-like behavior by L-PA was investigated. Chicks were injected i.c.v. with the GABA-A antagonist picrotoxin or GABA-B antagonist CGP54626 along with L-PA. Although suppression of food intake by L-PA was restored partially by co-injection with CGP54626, but not picrotoxin, sleep-like behavior induced by L-PA was suppressed significantly by both antagonists. These results suggested that L-PA activated both GABA-A and GABA-B receptors, and GABA-B receptors alone contributed to food intake whereas both receptors contributed to sleep-like behavior.
Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) which has a high nutritional content because it is rich in phytochemicals, and contains high concentrations of minerals and vitamins, carotenoid, dietary fiber, and antioxidant compounds, including polyphenols and phenolic acids (9, 18). Some epidemiological studies have provided sound scientific evidence that the regular consumption of Brassicaceae, including cabbage, broccoli, cauliflower and brussel sprouts, may be highly effective in reducing cancer risk (1,22,24,30). Brassicaceae plants contain a high amount of specific phytochemicals known as glucosinolates, a large group of sulfur-containing glucosides. Upon the disruption of plant tissues (food processing, chewing, etc.), glucosinolates come into contact with plant myrosinase, and then myrosinase catalyzes the conversion of glucosinolates to isothiocyanates (ITCs). There are various kinds of ITCs, phenethyl ITC (cabbage, watercress), benzyl ITC (papaya), allyl ITC (black mustard), and sulforaphane (broccoli), which have pungent components and a strong flavor that stimulates people's appetite. It has been known that ITCs contribute to the chemoprevention function of Brassicaceae by inducing phase 2 detoxication enzymes (e.g., UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs)), and they have attracted intense research interest (2,5,8,13,21,28). Whereas, there is possibility that Brassicaceae plants promote the conjugation of some drugs, and then decrease effects of drugs. Previous study showed that a diet containing cabbage induced the conjugation of acetaminophen (AA),
Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-promoting phytochemicals. There are many reports about the effects of kale ingestion on the chemoprevention function and mechanism, but the interactions between kale and drugs have not been researched. We investigated the effects of kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs, including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone (for CYP2E1). Cocktail drugs were administered into rats treated with kale and cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a significant increase in plasma levels and the AUC of midazolam, caffeine, and dextromethorphan. In addition, the plasma concentration and AUC of omeprazole tended to increase. Additionally, no almost differences in the mRNA expression levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion was considered to have an inhibitory effect on the activities of CYP3A4, 1A2, 2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the mRNA expressions.Kale (Brassica oleracea L. var acephala DC) is a cruciferous vegetable (Brassicaceae) which has a high nutritional content because it is rich in phytochemicals and contains high concentrations of minerals and vitamins, as well as carotenoid, dietary fiber, and antioxidative compounds, including polyphenols and phenolic acids (5, 10). Brassicaceae plants contain a high amount of specific phytochemicals known as glucosinolates, a large group of sulfur-containing glucosides. These compounds remain intact unless brought into contact with the enzyme myrosinase by pests, food processing, or chewing. Myrosinase releases glucose and breakdown products, including isothiocyanates (ITCs). There are various kinds of ITCs, phenethyl ITC (cabbage, watercress), benzyl ITC (papaya), allyl ITC (black mustard), and sulforaphane (broccoli), which have pungent components and a strong flavor that stimulates people's appetite. Many researchers have reported that ITCs have an inhibitory effect on cytochrome P450 (CYP) activities (3,4,7,8,16). In our previous study, we clarified that the ingestion of kale had changed the pharmacokinetic profiles of acetaminophen for a reason except its glucuronidation and sulfation (22). Acetaminophen mainly receives the actions of glucuronidation and sulfation by UDP-glucuronosyltransferases and sulfotransferase, and is excreted in urine. However, it has been known that acetaminophen is metabolized by CYP3A4, 1A2, 2D6 and 2E1 (2,6,9,11,18). Thus, CYP enzymes were suggested to be involved in the change of the pharmacokinetic profiles of ac-
Beneficial effects of sesame lignans, especially antioxidative effects, have been widely reported; however, its potential effects on autonomic nerves have not yet been investigated. Therefore, the current study aimed to investigate the effect of sesame lignans on the autonomic nervous system. The sympathetic nerve activity in rat skeletal muscle was measured using electrophysiological approaches, with blood flow determined using the laser Doppler method. Sesame lignans were administered intragastrically at 2 and 20 mg/kg, and after 60 min, the sympathetic nerve activity was observed to increase by 45.2 % and 66.1 %, respectively. A significant increase in blood flow (39.6 %) was also observed for the 20-mg/kg dose when measured at 55 min after administration. These sympathomimetic effects were completely prevented by subdiaphragmatic vagotomy, and the increase in blood flow was eliminated in the presence of the β2-adrenergic receptor inhibitor butoxamine. Thus, it is proposed that sesame lignans can increase the blood flow of skeletal muscle, possibly by exciting sympathetic nerve activity through the afferent vagal nerve.
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