cedrene and cedrol

Essential oil from Juniperus virginiana L. (eastern red cedarwood essential oil, CWO) has been used to relax mind and enhance comfort for medical purposes. Few reports showed its effect on anxiety behaviors in animal models. The present study investigated the anxiolytic effect of CWO using two anxiety tests in mice, then determined the major active constituents, examined the change of neurotransmitters after intraperitoneal (i.p.) administration. Analysis using GC/MS revealed that the CWO contained (-)-α-cedrene (28.11%), (+)-β-cedrene (7.81%), (-)-thujopsene (17.71%) and (+)-cedrol (24.58%). CWO at 400-800mg/kg increased the percentage of open arm entries and the percentage of the time spent in open arms in the elevated plus maze (EPM), suggesting that the oil has anxiolytic effect. However, it didn't show anxiolytic effect in the light-dark box (LDB) test. Tests of the cedrene did not show anxiolytic effect in either test, but rather induced anxiety-related behaviors and inhibited the locomotor activity in EPM and LDB. Cedrol produced significant anxiolytic effect in both EPM and LDB tests at 400-1600mg/kg and 800-1600mg/kg, respectively. A more significant increase in locomotor activity was observed in cedrol at 200-1600mg/kg administration than CWO. CWO increased the 5-hydroxytryptamine (5-HT) concentration at 800mg/kg, whereas it didn't affect the dopamine (DA) concentration. Cedrol significantly reduced the DA level at 100-200mg/kg and elevated the 5-HT level at 1200-1600mg/kg. Moreover, it changed the ratio of 5-hydroxyindoleacetic acid/5-HT and 3, 4-dihydroxyphenyl acetic acid/DA at 1200-1600mg/kg. CWO and cedrol, in particular might act in an anxiolytic effect through the 5-HTnergic and DAnergic pathways.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Anti-Anxiety Agents; Behavior, Animal; Brain; Dopamine; Dose-Response Relationship, Drug; Hydroxyindoleacetic Acid; Juniperus; Locomotion; Male; Maze Learning; Mice; Oils, Volatile; Polycyclic Sesquiterpenes; Serotonin; Sesquiterpenes; Terpenes

Complete and unambiguous

Topics: Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Conformation; Polycyclic Sesquiterpenes; Sesquiterpenes; Software; Terpenes

Cedrol, β-cedrene, and thujopsene are bioactive sesquiterpenes found in cedar essential oil and exert antiseptic, anti-inflammatory, antispasmodic, tonic, astringent, diuretic, sedative, insecticidal, and antifungal activities. These compounds are used globally in traditional medicine and cosmetics. The aim of this study was to investigate the inhibitory effects of cedrol, β-cedrene, and thujopsene on the activities of eight major human cytochrome P-450 (CYP) enzymes using human liver microsomes to assess potential β-cedrene-, cedrol-, and thujopsene-drug interactions. Cedrol, β-cedrene, and thujopsene were found to be potent competitive inhibitors of CYP2B6-mediated bupropion hydroxylase with inhibition constant (Ki) values of 0.9, 1.6, and 0.8 μM, respectively, comparable with that of a selective CYP2B6 inhibitor, thioTEPA (Ki, 2.9 μM). Cedrol also markedly inhibited CYP3A4-mediated midazolam hydroxylation with a Ki value of 3.4 μM, whereas β-cedrene and thujopsene moderately blocked CYP3A4. Cedrol, β-cedrene, and thujopsene at 100 μM negligibly inhibited CYP1A2, CYP2A6, and CYP2D6 activities. Only thujopsene was found to be a mechanism-based inhibitor of CYP2C8, CYP2C9, and CYP2C19. Cedrol and thujopsene weakly inhibited CYP2C8, CYP2C9, and CYP2C19 activities, but β-cedrene did not. These in vitro results indicate that cedrol, β-cedrene, and thujopsene need to be examined for potential pharmacokinetic drug interactions in vivo due to their potent inhibition of CYP2B6 and CYP3A4.

Topics: Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Microsomes, Liver; Polycyclic Sesquiterpenes; Sesquiterpenes; Terpenes