Pharmacokinetics Of The Major Chemical Constituents Of Scabiosa Comosa Flower After Gavaging Its Powder Or Extracts To Rats And The Influence Of Terminalia Chebula Fruit

Scabiosa comosa is a member of Dipsacaceae family.Its flower is a traditional Mongolian medicine named Sen–TaoRima.It is mainly produced in Inner Mongolia,Jilin,Heilongjiang,Liaoning and other places of China.According to the records in"Chinese Materia Medica",S.comosa and S.tschilliensis are widely used as a Mongolian medicine in China.The"Drug standards of Ministry of public health of China?Mongolian medicine Fascicule?,1998"stipulates that the inflorescences of both these plants could be used as the traditional medicine.This study applied UHPLC-MS to quantify the major bioactive constituents and optimized the ethanol extraction concentration for S.comosa flower.The differences in the contents of the constituents in the ethanol extract and the aqueous extract were analyzed and compared.A total of 12 compounds were detected as:chlorogenic acid,quinic acid,caffeic acid,p-counmaric acid,apigenin,apigenin-7-glucoside,apigenin-7-arabinose?1⁶?-glucoside,luteolin,luteolin-4?-glucosid,luteolin-7-glucoside,luteolin-6-C-glucoside and rutin.It was found that when the ethanol concentration was 50%,apigenin and luteolin showed the maximum peak areas in the UHPLC-MS,and the content of chlorogenic acid was also relatively high,and consequently,the optimal ethanol extraction concentration was determined as 50%.The pharmacokinetic properties of the bioactive constituents in S.comosa flower were investigated after gavaging to rats the flower powder or its extracts.It was found that 9 compounds could be detected in rat blood after gavaging the flower powder,while only 7 compounds could be detected in rat blood after gavaging the corresponding amounts of ethanol extract or water extract.Multiple peaks were observed in the drug-time curves of luteolin and apigenin,suggesting that some glycosides of the flavonoids could be decomposed to the aglycones in the intestine,and reabsorbed through hepatic intestinal circulation.When gavaging the corresponding amount of the water extract,apigenin,apigenin-7-glucoside,luteolin,luteolin-4'-O-glucoside,luteolin-7-O-glucose displayed larger C_maxax than those gavaged the flower powder,and the T_maxax were shorter in the water extract group than those in the powder group,indicating that the absorption was fast.As the fruit of Terminalia chebula is often formulated together with S.comosa flower in traditional Mongolian Medicines,experiments were designed to investigate the influence effects of T.chebula fruit on the pharmacokinetics of the main constituents of S.comosa flower.The experiment was divided into 3 groups using the herbal powder form which is the most commonly used dosing form in traditional Mongolian medicines:the S.comosa powder group,the T.chebula fruit powder group,and the mixture of S.comosa powder and T.chebula fruit powder group.The experimental results showed that in the T.chebula and S.comosa group,the T_maxax and CL/F of apigenin-7-arabinose?1⁶?-glucoside were shorter than those in single S.comosa powder group.In addition,the AUC value of this compound was greater than that in the S.comosa powder group.The results indicated that the bioavailability of the compound in the S.comosa and T.chebula mixed group is higher than that in single S.comosa powder group.For luteolin,the T_maxax value of the T.chebula and S.comosa group was greater than that in single S.comosa powder group,and the AUC value was smaller than that in single S.comosa powder group,which suggested that the chemical constituents in the fruit of T.chebula might have slowed down the absorption of luteolin.In conclusion,50%ethanol was found to be the optimum concentration for extracting the bioactive constituents of S.comosa flowers.Upon quantitative analysis of 12 major chemical constituents of S.comosa,the pharmacokinetics of the major chemical constituents were investigated.More chemical constituents were detected in rat blood after gavaging S.comosa flower powder than gvaging its extracts.The major constituents could be absorbed faster when gavaging the water extract.For the first time,the effects of T.chebula fruit on the pharmacokinetics of the flavonoids in S.comosa flower were investigated.It was found that when S.comosa flowers were combined with T.chebula fruit,the T_max,CL/F,and the AUC values of the major chemical constituents were altered.These results,taking S.comosa flower as an example,explained the scientific principle of the clinic practice of Mongolian medication to use the decoction at first to quickly exert the therapeutic effect and to use herbal powder afterward to maintain and enhance the effect.The results also provided scientific data to explain the principle of adjusting therapeutic efficacy by herbal drug combination,from the pharmacokinetic point of view.