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Background: Vitexin is the main bioactive compound of hawthorn (Crataegus pinnatifida), a famous traditional Chinese medicine, and vitexin for injection is currently in phase I clinical trial in China. Objective: This investigation systematically evaluated the metabolism and toxicokinetics of vitexin in rats and dogs. Methods: Rats and beagle dogs were administrated different doses of vitexin, and then the plasma concentration, tissue distribution, excretion, metabolism, pharmacokinetics and plasma protein binding were investigated. Results : The elimination half-life (t1/2) values in rats after a single intravenous dose of 3, 15 and 75 mg/kg were estimated as 43.53±10.82, 22.86±4.23, and 21.17±8.64 min, and the values of the area under the plasma concentration-time curve (AUC0→∞) were 329.34±144.07, 974.79±177.27, and 5251.49±786.98 mg•min/L, respectively. The plasma protein binding rate in rats was determined as about 65% by equilibrium dialysis after 72 hr. After 24 hr of intravenous administration, 16.30%, 3.47% and 9.72% of the given dose were excreted in urine, feces and bile, respectively. The metabolites of the vitexin were hydrolyzed via deglycosylation. The pharmacokinetics of dogs after intravenous administration revealed t1/2, AUC0-∞ and mean residence time (MRT0-∞) values of 20.43±6.37 min, 227.96±26.68 mg•min/L and 17.12±4.33 min, respectively. The no-observed-adverse- effect level (NOAEL) was 50 mg/kg body weight/day. There was no significant accumulation effect at 8 or 20 mg/kg/day in dogs over 92 days of repeated administration. For the 50 mg/kg/- day dose group, the exposure (AUC, Cmax) decreased significantly with prolonged administration. This trend suggests that repeated administration accelerates vitexin metabolism. Conclusion: The absorption of vitexin following routine oral administration was very low. To improve the bioavailability of vitexin, the development of an injectable formulation would be a suitable alternative choice.

Qingnaopian has been used in traditional Chinese medicine for treating central nervous system (CNS) injury and inflammatory diseases. The aim of this study was to investigate the effects of Qingnaopian in concussion mice. C57BL/6 mice were used to establish the mild Traumatic Brain Injury (mTBI)/ concussion using the weight-drop techniques. Animal behavioral experiments righting reflex response and locomotor activity were assessed. The expression of pro inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1 and Glial fibrillary acidic protein (GFAP) were assessed by enzyme-linked immunosorbent assay (ELISA) and Western blot method, respectively. SPSS 19.0 software was used for statistical analysis. The results showed that righting reflex time and locomotor activity were higher in model group compared with those in control group. Qingnaopian treated mice had lower pro inflammatory cytokines, such as IL-1, IL-6 and TNF-α with alleviated GFAP. In short, Qingnaopian treatment improved GFAP induced by blow to head and inflammatory cytokines in concussion mice.