| Acacia catechu(L.f.)Willd compatibility with Scutellaria baicalensis Georgi,both of them could clearing away the lung-heat,it is used to play the efficacy of clearing heat and transforming phlegm.At the same time,the compatibility is used to treat cough,phlegm and fever.However,the chemical composition of the compatibility is complex,and there has been a lack of clear mechanism for the treatment of hyperactivity cough,which limits its further application.In this study,the traditional way of administration of traditional Chinese medicine was simulated through the preparation of extract.Based on that,we studied the pharmacokinetics and pharmacology of the main components of herb compatibility.The effective substance of compatibility in vivo is preliminarily described.1.Preparation and content determination of Acacia catechu(L.f.)Willd extracts and Scutellaria baicalensis Georgi extracts: two herbs were extracted via sonication with 75% ethanol.Meanwhile,a HPLC method was established for the determination of the content of(+)-catechin and(-)-epicatechin in Acacia catechu(L.f.)Willd and the content of baicalin and baicalein in Scutellaria baicalensis Georgi.2.An LC-MS/MS method for simultaneous determination of(+)-catechin,(-)-epicatechin,baicalin,baicalein and EGCG(internal standard)in plasma was established.The method was applied to the pharmacokinetics of two extracts after oral administration in rats.The absorption of(+)-catechin,(-)-epicatechin and baicalin in rats was significantly inhibited,but the duration of action in the body was also prolonged after compatible administration.3.We established the LC-MS/MS method to determine the tissue distribution dynamics of heart,liver,spleen,lung,kidney,brain,stomach,and intestine after oral administration of Acacia catechu(L.f.)Willd and Scutellaria baicalensis Georgi extracts in rats.The results showed that the contents of(+)-catechin,(-)-epicatechin and baicalin in the gastrointestinal tissue of the compatible administration group were significantly lower than those of the single administration group,however,the(+)-catechin and(-)-epicatechin in the liver and lung tissues were significantly increased.The results show that the interactions between herbs are related to the competitive absorption inhibitory effects of the gastrointestinal tract.Moreover,the alteration of(+)-catechin and(-)-epicatechin in the tissue of lung maybe could enhance the pharmacological activity for treating pulmonary infection.In addition,by comparing the profiles of(+)-catechin,(-)-epicatechin,baicalin and baicalein in urine and feces following single and compatible administration of Acacia catechu(L.f.)Willd or Scutellaria baicalensis Georgi,the recoveries of the four active ingredients significantly increased.Similar polyphenolic chemical structures might appeared competitive inhibition in kidney lead to the decline renal tubular reabsorption,resulting in urinary excretion of components was significantly increased.4.An acute pneumonia model was established by intranasally instillation of LPS in rats,rats from pretreatment groups were pretreated with herbal extracts for one week before modeling.ELISA method was used to detect the contents of TNF-? and IL-1? in BALF of rats,histological changes were assessed to study lung injuries,based on these results,we investigated the possible protecting mechanism of herbal extracts on the inflammation induced by LPS stimulation.We isolated and cultured rat alveolar type?epithelial cells(AT?),and screened the appropriate drug concentration by MTT.Low,medium and high concentrations of herbal extracts can significantly reduce the levels of inflammatory cytokines IL-1?,IL-4,IL-6,IL-10 and IFN-?in rat AEC?,Q-PCR results showed that the expression of several inflammatory factors was also significantly inhibited.The expression of NF-?B p50,p65 and I?B-? was measured by western blot.The expression of NF-?B p50,p65 and I?B-? was significantly increased in cells after stimulated by LPS.Low,medium and high concentrations of herbal extracts can significantly reduce the expression of NF-?B p50,p65 and I?B-? in the cells,there was no statistical difference between the high dose group and the dexamethasone group.Acacia catechu(L.f.)Willd-Scutellaria baicalensis Georgi inhibits the expression of NF-?B signal pathway and inhibits the expression of inflammatory factors to improve pulmonary inflammation.We prepared two kinds of extracts of Acacia catechu(L.f.)Willd and Scutellaria baicalensis Georgi,and selected four main chemical components as research indicators.Rats were used as experimental models to study the pharmacokinetics,tissue distribution and excretion in vivo.The results demonstrate that herb –herb interactions occurred in this herb couple and it has targeting therapeutic effect on lung tissue.Meanwhile,we also confirmed that herb couple has significant anti-inflammatory effects in lung tissue,its mechanism is related to the regulation of inhibition of NF-?B signaling pathway.The results of present study provide an experimental evidence to the pharmacological mechanism and scientificity,which lays a foundation for further development of the herb couple. |
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