Effects of Kaixin Jieyu Decoction () on behavior, monoamine neurotransmitter levels, and serotonin receptor subtype expression in the brain of a rat depression model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior, monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype expression in the brain in a rat model of depression.</p><p><b>METHODS</b>The rat depression model was established using chronic unpredictable mild stress (CUMS). Forty-eight Sprague Dawley rats were randomly divided into control, depression model (CUMS), CUMS+KJD (7.7 g/kg(-1)·d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(-1)·d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptor mRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.</p><p><b>RESULTS</b>Compared with the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expression was higher than in the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially attenuated these changes (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.</p>

CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.</p><p><b>METHOD</b>Cocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes.</p><p><b>RESULT</b>Compared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).</p><p><b>CONCLUSION</b>Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.</p>