OBJECTIVE:To study the effects of Heishun tablets combined with Rheum palmatum on the pharmacokinetics of hypaconitine in rats. METHODS:Rats were randomly divided into single drug group(Heishun tablets decoction)and drug combi-nation group(Heishun tablets-R. palmatum mixture decoction),with 18 rats in each group. They were given relevant drugs intragas-trically,by 10 g(medicinal materials)/kg of Heishun tablets. 0.3 ml blood samples were collected before(0 h)and 0.083,0.167, 0.333,0.5,0.75,1,1.5,2,3,4,6,8,10 h after medication with 6 rats at each time point,respectively. The blood concentra-tion of hypaconitine was determined by HPLC-MS using palmatine hydrochloride as internal standard. DAS 2.0.1 software was used to calculate pharmacokinetic parameters. RESULTS:The linear range of hypaconitine was 0.102 4-100 ng/ml (r=0.998 7),and the limit of quantification was 0.1 ng/ml. The pharmacokinetic parameters of single drug group vs. drug combination group were as follows as tmax of (0.50 ± 0.086) h vs. (0.75 ± 0.132)h;t1/2 of (9.967 ± 1.123) h vs. (3.708 ± 0.507) h;AUC0-10 h of (26.087 ± 0.672) μg·h/L vs.(6.516 ± 1.135) μg·h/L;cmax of (6.124 ± 2.312) μg/L vs. (1.592 ± 0.051) μg/L. Compared with single drug group,t1/2,AUC0-10 h and cmax of hypaconitine were decreased in drug combination group,with statistical significance (P<0.05). CONCLUSIONS:R. palmatum can inhibit the absorption of hypaconitine in rats,and speed up the elimination of it in rats.

Objective: To investigate the therapeutic effect of Jin Long Capsule (JLC) combined with neoadjuvant chemotherapy on the invasive breast cancer, and to explore the mechanism of JLC in inhibiting multidrug resistance of breast cancer. Methods: 200 patients were divided into experimental group and control group (100 cases per group). The control group used TEC regimen for neoadjuvant chemotherapy. And the experimental group was treated with TEC regimen combined with oral JLC. According to the Miller & Payne grading system (MP), the efficacy of neoadjuvant chemotherapy was evaluated based on histopathological changes of breast cancer after neoadjuvant chemotherapy. Adverse effect was evaluated according to the classification criteria of the National Cancer Institute of the United States-The Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The expression of P-glycoprotein (P-gp), glutathione thiol transferase (GST)-π and topoisomerase Ⅱα (TopoⅡα) in breast cancer tissues before and after neoadjuvant chemotherapy were detected by immunohistochemical staining. Results: There were 83 effective cases (83%) in the experimental group, which was higher than that in the control group (65.0%, P<0.05). The incidence of leukopenia, gastrointestinal reactions and alopecia in grade 3 to 4 of the experimental group were lower than those of the control group (all P<0.05). The positive rates of P-gp, GST-π and TopoⅡα expression in the control group were 65.0% (65/100), 61.0% (61/100) and 69.0% (69/100), respectively, and they were 80.6% (75/93), 78.5% (73/93) and 37.6% (35/93) after chemotherapy. The positive rates of P-gp and GST-π expression were significantly higher than those before chemotherapy (both P<0.05), whereas the positive rate of TopoⅡα expression was significantly lower than that before chemotherapy (P<0.05). In the experimental group, the positive rates of P-gp, GST-π and TopoⅡα expression before chemotherapy were 62.0% (62/100), 63.0% (63/100) and 69.0% (69/100), respectively, while after chemotherapy, they were 68.2% (60/88), 67.0% (59/88) and 63.6% (56/88). There was no significant difference in the positive rates and expression intensity of P-gp, GST-π and TopoⅡα before and after the chemotherapy (P>0.05). Conclusion Jin Long Capsule (JLC) can inhibit multidrug resistance, improve the efficacy of neoadjuvant chemotherapy, and reduce adverse reactions of breast cancer.