Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats / 中国中药杂志

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Effect of Tongxie Yaofang with or Without Saposhnikoviae Radix on Water Metabolism and 5-HT Pathway in Irritable Bowel Syndrome Rats / 中国实验方剂学杂志

Objective:To investigate the effect of Saposhnikoviae Radix on Tongxie Yaofang in regulating water metabolism and 5-serotonin（5-HT） signal system in diarrhea type irritable bowel syndrome（IBS-D）rats. Method:The 40 IBS-D SD rats were randomly divided into model group, Tongxie Yaofang wituout Saposhnikoviae Radix group (26 g·kg-1), Tongxie Yaofang decoction group (30 g·kg-1), Tongxie Yaofang with double Saposhnikoviae Radix group (34 g·kg-1),another 10 normal SD rats were selected as the normal group.Except for normal group, the rats in other groups were separated from their mothers and induced by acetic acid to establish D-IBS model. These rats in the each group were administered with corresponding drugs for 14 days. The diarrhea indexs and the water contents of the feces were observed and calculated. The Na+-K+-ATPase activities in the intestinal mucosa were detected by micro method. The contents of 5-HT were detected by enzyme linked immunosorbent assay (ELISA). The activities of monoamine oxidase A (MAO-A) were detected by chemiluminescence method. The expressions of aquaporin 4 (AQP4) in colon were detected by immunohistochemistry. Protein expression levels of HT receptor 3 (5-HT3R), HT receptor 4 (5-HT4R) and serotonin transporter (SERT) in hypothalamus and colon were detected by Western blot. Result:Compared with normal group, the fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT3R were significantly increased in model group (P<0.01), and the activities of Na+-K+-ATPase, expressions of AQP4, 5-HT4R and SERT were reduced significantly (P<0.01). Compared with model group, the diarrhea indexs and fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT3R were significantly decreased in each experimental group, and the activities of Na+-K+-ATPase, expressions of AQP4,5-HT4R and SERT were significantly increased(P<0.05，P<0.01),however, there was no significant difference in the expression of 5-HT3R protein in Tongxie Yaofang wituout Saposhnikoviae Radix group.Compared with Tongxie Yaofang wituout Saposhnikoviae Radix group,the diarrhea index, fecal water content, 5-HT content, MAO-A enzyme activity, and protein expression of 5-HT3R were significantly decreased in Tongxie Yaofang group and Tongxie Yaofang with double Saposhnikoviae Radix group(P<0.05，P<0.01), and the activity of Na+-K+-ATPase and protein expression of SERT were significantly increased(P<0.05，P<0.01). Conclusion:Saposhnikoviae Radix can enhance the effects of Tongxie Yaofang on improving the water metabolism of rats with IBS-D and regulating the multi-target of 5-HT signaling system, further confirming the synergistic effect of Saposhnikoviae Radix.