Metabolic Interaction of the Active Constituents of Coptis chinensis

Coptis chinensis is commonly used in traditional Chinese medicine. The study investigated metabolic interaction of the active constituents (berberine, coptisine, palmatine, and jatrorrhizine) of Coptis chinensis in human liver microsomes. After incubation of the four constituents of Coptis chinensis in HLMs, the metabolism of the four constituents was observed by HPLC. The in vitro inhibition experiment between the active constituents was conducted, and IC50 value was estimated. Coptisine exhibited inhibitions against the formation of the two metabolites of berberine with IC50 values of 6.5 and 8.3 μM, respectively. Palmatine and jatrorrhizine showed the weaker inhibitory effect on the formation of the metabolites of berberine. Berberine showed a weak inhibitory effect on the production of coptisine metabolite with an IC50 value of 115 μM, and palmatine and jatrorrhizine had little inhibitory effect on the formation of coptisine metabolite. Berberine, coptisine, and jatrorrhizine showed no inhibitory effect on the generation of palmatine metabolite (IC50 > 200 μM). The findings suggested that there are different degrees of metabolic interaction between the four components. Coptisine showed the strongest inhibition toward berberine metabolism

Effects of Danshen Ethanol Extract on the Pharmacokinetics of Fexofenadine in Healthy Volunteers

This study investigated the effect of multidose administration of danshen ethanol extract on fexofenadine pharmacokinetics in healthy volunteers. A sequential, open-label, two-period pharmacokinetic interaction design was used. 12 healthy male volunteers received a single oral dose of fexofenadine (60 mg) followed by danshen ethanol extract (1 g orally, three times a day) for 10 days, after which they received 1 g of the danshen extract with fexofenadine (60 mg) on the last day. The plasma concentrations of fexofenadine was measured by LC-MS/MS. After 10 days of the danshen extract administration, the mean AUC and max of the fexofenadine was decreased by 37.2% and 27.4% compared with the control, respectively. The mean clearance of fexofenadine was increased by 104.9%. The in vitro study showed that tanshinone IIA and cryptotanshinone could induce MDR1 mRNA. This study showed that multidose administration of danshen ethanol extract could increase oral clearance of fexofenadine. The increased oral clearance of fexofenadine is attributable to induction of intestinal P-glycoprotein

Effects of Danshen Ethanol Extract on the Pharmacokinetics of Fexofenadine in Healthy Volunteers

This study investigated the effect of multidose administration of danshen ethanol extract on fexofenadine pharmacokinetics in healthy volunteers. A sequential, open-label, two-period pharmacokinetic interaction design was used. 12 healthy male volunteers received a single oral dose of fexofenadine (60 mg) followed by danshen ethanol extract (1 g orally, three times a day) for 10 days, after which they received 1 g of the danshen extract with fexofenadine (60 mg) on the last day. The plasma concentrations of fexofenadine was measured by LC-MS/MS. After 10 days of the danshen extract administration, the mean AUC and Cmax⁡ of the fexofenadine was decreased by 37.2% and 27.4% compared with the control, respectively. The mean clearance of fexofenadine was increased by 104.9%. The in vitro study showed that tanshinone IIA and cryptotanshinone could induce MDR1 mRNA. This study showed that multidose administration of danshen ethanol extract could increase oral clearance of fexofenadine. The increased oral clearance of fexofenadine is attributable to induction of intestinal P-glycoprotein

Chaihu-Shugan-San administration ameliorates perimenopausal anxiety and depression in rats.

Chaihu-Shugan-San (CSS) is a traditional Chinese herbal formula that is widely used for treating perimenopausal symptoms in China; however, its mechanisms remain unknown. The present study was designed to investigate potential CSS mechanisms in rats with unpredicted chronic mild stress (UCMS) and normally aging rats (52 weeks of age). We performed the sucrose consumption test along with the forced swimming test to confirm depression-like behavior and the open field test (OFT) to confirm anxiety-like behavior in the animals. In addition, we used an enzyme-linked immunosorbent assay to measure serum and hippocampal estradiol (E2) levels and a quantitative real-time polymerase chain reaction to assess hippocampal mRNA levels of estrogen receptors (ERs) α and β as well as G protein-coupled receptor 30 (GPR30). We found that CSS administration resulted in a significant increase in the ratio of hippocampal ERα and ERβ mRNA (ERα/ERβ ratio) in UCMS rats (p<0.001). However, no significant changes were observed in E2 levels, ERα mRNA expression, and GPR30 mRNA expression. In contrast, changes in ERα/ERβ mRNA ratio were sensitively associated with changes in mood states in the animal models. These findings suggest that enhancement of ERα/ERβ ratio may play a role in the pharmacological mechanisms of CSS. Furthermore, this ratio can be employed as a potential index for evaluating mood states in animal models and can be considered as a therapeutic target for perimenopausal anxiety and depression in the future

Behavioral tests for depression-like behavior in rats.

<p>A. Results of the sucrose consumption test. Sucrose intake was significantly decreased in the UCMS without CSS group compared with that in the ACON without CSS groups (<i>p</i><0.001). On the other hand, sucrose intake in the UCMS with CSS group was significantly increased compared with that in the UCMS without CSS (<i>p</i><0.001) group. B: Results of the forced swimming test (FST). The immobility time was significantly longer in the UCMS without CSS group than in the ACON without CSS group (<i>p</i><0.001). However, immobility time in the UCMS with CSS group was significantly shorter than that in the UCMS without CSS group (<i>p</i><0.005). The depressive state in the UCMS rats was verified (ACON without CSS vs. UCMS without CSS). CSS administration was effective for treating depressive symptoms in the UCMS rats (UCMS with CSS vs. UCMS without CSS). Values are means ± SEM. *<i>p</i><0.005, **<i>p</i><0.001. The <i>p</i>-value was established by analysis of variance (ANOVA). The post-hoc Bonferroni test was not applied when the <i>p</i>-value was >0.05 as per ANOVA).</p

Serum and Hippocampal E₂ levels.

<p>The results for serum (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072428#pone-0072428-g005" target="_blank">Figure 5A</a>.) and hippocampal (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072428#pone-0072428-g005" target="_blank">Figure 5B</a>.) E₂ levels were analogous. The E₂ levels in the CON group were significantly higher than those in the other groups (<i>p</i><0.001), but no difference was observed among the other groups. Values are means ± SEM. **<i>p</i><0.001. The <i>p</i>-value was established by analysis of variance (ANOVA). The post-hoc Bonferroni test was not applied when the <i>p</i>-value was >0.05 as per ANOVA).</p

The ingredients of the Chaihu-Shugan-San (CSS) solution.

<p>The ingredients of the Chaihu-Shugan-San (CSS) solution.</p

Protocol for the behavioral tests.

<p>The interval between the blocks was 1 day.</p

Primers for quantitative real-time RT-PCR (Rat).

<p>Primers for quantitative real-time RT-PCR (Rat).</p