IN VIVO EFFECT OF GUIDING-HERB RADIX PLATYCODONIS AND RADIX CYATHULAE ON PAEONIFLORIN PHARMACOKINETICS OF XUEFU ZHUYU TANG IN RATS.

BACKGROUND: Xuefu Zhuyu Tang (XFZYT), first recorded in Correction of Errors in Medical Works by Qing-ren Wang, has been proven reliable and effective for curing various diseases such as atherosclerosis, hypertension, hyperlipidemia, and angina pectoris. It consists of 11 herbs and two of them, Radix platycodonis and Radix cyathulae, have been traditionally considered as guiding herbs and deeply valued by tens of millions of Chinese medicine practitioners. Do Radix platycodonis and Radix cyathulae affect the pharmacokinetics of the effective constituent-paeoniflorin of XFZYT? If yes, in what way? This study aims to answer these questions. MATERIALS AND METHODS: The medicinal solutions of XFZYT, XFZYT without Radix platycodonis (XFZYT-JG), XFZYT without Radix cyathulae (XFZYT-NX), and XFZYT without Radix platycodonis and Radix cyathulae (XFZYT-JG-NX) were prepared and administrated to rats in the normal group and the blood-stasis model group by gavage, respectively. The blood samples of rats in the normal group were obtained 5, 10, 15, 20, 30, 45, 60, 120, and 240 minutes after gavage; whereas the blood samples of rats in the blood-stasis model group were obtained 10, 15, 20, 30, 45, 90, 150, and 240 minutes after gavage. Biological samples were processed; the assays of specificity, precision, linearity, intra-day and inter-day precisions, recovery and stability were conducted; high performance liquid chromatography was performed to detect paeoniflorin content; and DAS software was adopted to generate pharmacokinetic parameters. Mobile phase was composed of acetonitrile and water (16:84), detection wavelength was 230 nm, and riboflavin was set as internal standard substance. RESULTS: The pharmacokinetic parameters of the rats in the normal group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.363±0.248, 0.065±0.020, 0.099±0.033, 0.099±0.020) mg/L, Tmax = (0.276±0.084, 0.583±0.342, 0.555±0.228, 0.317±0.033)h, t1/2 = (0.501±0.241, 1.021±0.522, 0.853±0.377, 1.227±0.402) h; and AUC0-∞ = (0.381±0.415, 0.13±0.085, 0.166±0.066, 0.185±0.059) mg/L·h.; whereas the pharmacokinetic parameters for the rats in the blood-stasis model group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.315±0.153, 0.215±0.044, 0.228±0.056, 0.248±0.09) mg/L, Tmax = (0.5±0, 0.667±0.129, 0.5±0, 0.542±0.102) h, t1/2 = (0.408±0.146, 0.813±0.135, 0.708±0.383, 0.741±0.173) h, and AUC0-∞ = (0.306±0.157, 0.408±0.136, 0.368±0.159, 0.381±0.246) mg/L·h. CONCLUSION: The guiding herbs, Radix platycodonis and Radix cyathulae, significantly increased the absorption amount and rate of paeoniflorin in XFZYT, and accelerated its elimination from the blood.

[Effects of Jinmaitong capsule on nerve growth factor in diabetic rats].

OBJECTIVE: To study the effects of Jinmaitong Capsule (JMT) on the expression of NGF and NGF mRNA in STZ-induced diabetic rats. METHOD: Fifty SZT-induced diabetic rats were randomly divided into 5 groups including model group, low-dose JMT group (treated with JMT similar to the quintupling dose of adult recommended dosage), middle-dose JMT group (treated with JMT similar to the decuple dose of adult recommended dosage), high-dose JMT group (treated with JMT similar to the twenty-fold dose of adult recommended dosage) and Neurotropin group (treated with Neurotropin similar to the decuple dose of adult recommended dosage). Ten normal rats matching with weight and age served as normal control group. All rats were given intragastric administration for 16 weeks and then killed. Body weight and blood glucose were detected before and at the 4, 8, 12, 16th week after treatment. The hydrothermal tail-flick and pain threshold to mechanical stimulation with Von Frey filament were carried out before death. The expression of NGF and NGF-mRNA in sciatic nerve were detected by SABC immunohistochemical method and real-time fluorogenetic quantitative PCR respectively. RESULT: The blood glucose levels of STZ-DM rats were much higher than those of normal rats (P < 0.01). In all the treated groups, there were no significant differences among them compared each other or compared with model group. And it got the same result when concerning about body weight no matter how the rats were dealt with. Hydrothermal tail-flick test: The tail-flick latency of STZ-DM rats were much longer than those of normal rats (P < 0.01 or P < 0.05). Compared with model group, the time shortened significantly in low, middle-dose of JMT groups and Neutrophin group. Compared with normal group, the pain thresholds of model group decreased extremely (P < 0.01). Compared with model group, the threshold values of low-dose, middle-dose JMT group and neutrophin group raised strikingly (P < 0.05). The levels of NGF-mRNA expression in STZ-DM rats were much lower than those of the normal rats (P < 0.01). Compared with model group, NGF-mRNA expression of middle-dose JMT group and Neurotropin group upregulated noticeably (P < 0.01). The integrated option density of NGF expression in STZ-DM rats was much lower than the normal (P < 0.01 or P < 0.05). And the levels of NGF in all the treated groups increased notably compared with model group (P < 0.05 or P < 0.01). There were no significant differences among middle-dose JMT group and Neutrophin group. CONCLUSION: Traditional Chinese medicine JMT could up-regulate the expression of NGF and NGF-mRNA in sciatic nerve.