Druggability is crucial in pharmaceutical drug development as the source of drug research. Druggability research will face greater challenges because Chinese materia medica (CMM) is the multicomponent drug. In this paper, ideas and methods of study on CMM druggability were mainly proposed in combination with the chemical material basis of muticomponents of CMM.

Objective To study the multicomponent in vivo dynamic process in Chuanxiong Rhizoma;To elaborate in vivo metabolic profiling. Methods HPLC was used to establish the fingerprint of aqueous extract of Chuanxiong Rhizoma, and multicomponent changes were detected at the same time. Closed-loop intestine method was used to study the multicomponent changes of oral administration of Chuanxiong Rhizoma after stomach-intestine-liver process. Results Totally 17 components were detected in the fingerprint of aqueous extract of Chuanxiong Rhizoma and they were basically stable in the digestive juice. For in vivo metabolism, 4 components were metabolized by intestinal flora;3 components were metabolized by liver;2 new components were the metabolites of intestinal flora;1 component was the metabolite of liver. Conclusion Multicomponent sequential metabolism and closed-loop intestine method were used to clarify that multicomponent metabolic profiling was feasible, and it could provide experimental basis for the metabolism of traditional Chinese medicine.

Objective To select the components for quality control of Fructus Lycii based on the absorption of its extract. Methods To investigate metabolism of components of Fructus Lycii, everted rat gut sacs was carried out as well as the blood was taken from abdominal aorta,.and all samples were analysised by HPLC. Results There are twelve constituents absorbed between ileum and jejunum of rat , and four constituents were detected in the blood. Compound 2, 3, 4, 5, 6, 9, 10, 11 were absorbed in prototype forms in the intestine directly,and compound 1, 7, 8, 12 were new ones. On the other hand, four compositions(3, 7, 10, 13)could be absorbed into blood through analysis serum samples obtaining from aorta abdominalis of rats. Two of them (3, 10)could be absorbed directly by intestine, while(7)was absorbed into blood in new form . Conclusion Based on the intestinal absorption experiment and analysion of compsition in blood, components (3, 10, 13) can be the quality control ingredients of Fructus Lycii.

Objective This paper was to study the absorption and metabolism differences of intestine and liver for multicomponent licorice.Methods The components were identified with the UPLC-MS/MS. In situ closed-loop method was used to carry out the comparative experiments of absorption and metabolism differences between intestine and liver.Results 13 components were identified by UPLC-MS/MS. The absorption and metabolism results indicated some components in licorice water extract could be absorbed into blood and metabolism happened during this process. 14 metabolites were detected in the plasma sample. The hepatic metabolism results indicated many components could experience complex metabolism and more metabolites could be generated.Conclusions Liver was the major metabolism organ for licorice water extract and some components could be metabolized along with the absorption process in intestine. The absorption and metabolism differences between intestine and liver were significant.

Objective To investigate dynamic metabolism in vivo of Ginkgo Folium Tablet under the guidance of sequential metabolism thoughts. Methods In situ closed-loop in rats was carried out to study sequential metabolism of Ginkgo Folium Tablet through oral digestive system, namely to investigate and compare the intestinal flora metabolism, the gut wall metabolism and hepatic metabolism, combined with chromatographic fingerprint of blood samples. Results The analysis showed that 12 peaks in Ginkgo Folium Tablet were metabolized by intestinal flora, and 7 peaks generated through the gut wall. Most components of Ginkgo Folium Tablet were metabolized in liver, and 3 original medicine components were directly into the blood. Conclusion This study conducts a qualitative description of metabolism of Ginkgo Folium Tablet in different parts of the oral route, and provides references for the quality control, mechanism explanation and secondary development for Ginkgo Folium Tablet.

This study was aimed to determine the solubility an d oil-water partition coefficient of main active com-ponents in Ge-Gen Qin-Lian (GGQL) Tablets (puerarin, baicalin and berberine hydrochloride) in phosphate buffer solution of different pH values and under the background of many components. Solubility of puerarin, baicalin and berberine hydrochloride in different medium pH, and oil-water partition coefficient of the octanol-water and oc-tanol-buffer system were determined by HPLC method. The results showed that the solubility and oil-water partition coefficient of puerarin, baicalin and berberine hydrochloride were varied with the change of pH, and varied under the background of components. At pH 7.4, the solubility was the biggest;puerarin was 7.56 mg·mL-1;baicalin was 17.07 mg·mL-1; berberine hydrochloride was 3.57 mg·mL-1. Oil-water partition coefficient P of these components at pH 1.0 was bigger;puerarin was 0.420 (lgP=-0.38);baicalin was 10.783 (lgP=1.03);berberine hydrochloride was 0.267 (lgP=-0.57). It was concluded that lipid solubility of puerarin, baicalin and berberine hydrochloride at pH 1.0 was better. It was speculated that better absorption in the stomach, and low lipid solubility under other pH. It was speculated that lipid solubility may be one of the reasons affecting the intestinal absorption.

Objective To compare the dissolution of Chuangxiong powder in different medium and discuss the dissolution characteristics in vitro of Changxiong powder. Methods The paddle method was adopted, the UV spectrophotometric method was developed to determine the in vitro dissolution quantity of Changxiong powder in five medium (water, 0.1 mol/L hydrochloric acid, acetate buffer of pH 4.5, phosphate buffer of pH 6.8, phosphate buffer of pH 7.4) with ferulic acid as index, and evaluated by drawing the dissolution curve and using the similar factor method and Weibull model. Results The dissolution quantity of Changxiong oral powder in five medium was different. The dissolution quantity in water, 0.1 mol/L hydrochloric acid, acetate buffer of pH 4.5 and phosphate buffer of pH 6.8 was similar and fit Weibull model, but it mutated in phosphate buffer of pH 7.4 and reached the maximum amount at 30 min. Conclusion The dissolution quantity of Changxiong powder is gradually increasing and the time is shorted in the medium from acidic to neutral then to alkaline. Dissolution curve is similar in the acidic and neutral medium. Changxiong powder dissolves out fast and completely in the alkaline medium.

Congenital cleft lip and/or palate (CL/P) is a common malformation of maxillofacial development. At present, it is believed that the etiology of congenital cleft lip and palate mainly results from genetic factors and environmental factors. Epigenetic changes induced by environmental factors may be the key factor in the occurrence of fetal congenital malformations. As one of the important epigenetic modifications, DNA methylation has been widely and deeply studied in many fields, but as a link between the individual and the environment, its application in CL/P is limited. Existing studies have shown that DNA methylation is closely related to the occurrence of cleft lip and palate. Stimulation of folate deficiency, smoking, pollutant exposure and other environmental factors can induce changes in the state of DNA methylation, thus affecting gene expression in the development of lip and palate and leading to the occurrence of deformities.

Objective To investigate the effect of transcription factor specific protein5(Sp5)silencing on Wnt signaling pathway correlated factors and cell proliferation ability in mouse embryo palatal mesenchymal cells(mEPMCs).Methods mEPMCs of 14.5 d pregnant C57BL/6J mice were isolated and cultured in vitro.Cell source was identified by immunofluorescence staining.Lentivirus transfection technique was used to silence the expression of Sp5 gene in mEPMCs,and the transfection efficiency was verified by Western blot assay.Follow-up experiments were set up with the blank control group,the no-load virus group and the slience group(the Sp5-shRNA group).The protein and mRNA expression levels of β-catenin,GSK-3β,Wnt3a and CyclinD1 were detected by Western blot assay and RT-qPCR after transfection for 72 h in each group.Cell proliferation capacity was detected by CCK-8.The proliferation rate of 5-Ethynyl-2'-deoxyuridine(EdU)positive cells was detected by immunofluorescence assay.Cell cycle was detected by flow cytometry.Results mEPMCs were successfully isolated,and Sp5 expression was silenced.Western blot and RT-qPCR results showed that the protein and mRNA expressions of β-catenin,GSK-3β,Wnt3a and CyclinD1 were significantly higher in the Sp5-shRNA group than those in the blank control group and the no-loaded virus group(P<0.05).The proliferative ability and the proliferative rate of EdU positive cells were higher in the Sp5-shRNA group than those in the blank control group and the no-loaded virus group(P<0.05).The proportion of mEPMCs in S phase was higher in the Sp5-shRNA group than that in the blank control group and the no-loaded virus group(P<0.05).Conclusion Sp5 in silenced mEPMCs can participate in palate development and promote the proliferation of mEPMCs by regulating Wnt signaling pathway.

AIM: To establish a method to investigate pharmacokinetics and bioequivalence of buthlphthalide injection. METHODS: An open, randomized, and two-cycle crossover study was conducted in 24 healthy volunteers. Plasma concentrations of buthlphthalide were determined by LC-MS/MS after administering a single dose of reference drug or test drug. Main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. RESULTS: For the test drug and the reference drug, the main pharmacokinetic parameters of flurbiprofen were as follows: AUC