[Improving comprehensive retention rate of peppermint oil in freeze-dried preparation based on cyclodextrin inclusion technology].

The freeze-drying technique, characterized by low-temperature processing, is especially suitable for sensitive volatile oils with thermal instability. However, there are few studies focusing on the retention of volatile oils in the processing of freeze-dried preparations. This study evaluated the effects of different addition methods(adsorption, emulsification, solid dispersion, and inclusion) on the retention rate of the main components in peppermint oil, aiming to explore the application feasibility of freeze-dried preparations of volatile oils. Firstly, the addition method was determined based on the retention rates of menthol in four freeze-dried preparations. Secondly, an orthogonal test was designed to optimize the preparation process based on the characteristics of the preferred addition method. The results showed that the most suitable preparation form of peppermint oil was inclusion with beta-cyclodextrin(ß-CD), and the retention rate of menthol in freeze-drying was 86.36%. According to the two-step preparation process of inclusion and freeze-drying, we introduced the product of inclusion rate and retention rate, i.e., comprehensive retention rate, to determine the optimum processing parameters. The results showed that ß-CD/oil ratio of 7∶1, inclusion temperature of 40 ℃, and inclusion time of 2 h were the optimum processing parameters. The product prepared with these parameter had the comprehensive retention rate of 68.41%, retention rate of 92.53%, and inclusion rate of 73.93%. The inclusion compound was white powder with significantly increased solubility. The pre-paration process based on cyclodextrin inclusion in this study is stable and reliable and provides a new idea for ensuring the efficacy and stability of volatile components in freeze-dried preparations.

[Molecular mechanism of Qishen Yiqi Dripping Pills in treating myocardial ischemia:a study based on HIF-1 signaling pathway].

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.

Exploring the synergistic mechanism of Gegen Qinlian Decoction on the Wnt signaling pathway using an integrated strategy of network pharmacology and RNA-seq.

ETHNOPHARMACOLOGICAL RELEVANCE: Gegen Qinlian Decoction (GQD) (including: Puerariae lobatae (Willd.) Ohwi, radix; (short for Gengen) Glycyrrhiza uralensis Fisch., root and rhizome (short for Gancao), honeyed; Coptis chinensis Franch., rhizome (short for Huanglian); Scutellaria baicalensis Georgi, radix, boiled (short for S. baicalensis) has been widely used to treat inflammatory bowel disease (IBD) and colorectal cancer (CRC). To explore compatibility mechanism of GQD could be of advantage to investigate the complex principle of TCM, which might be conducive to the exploration of the modernization of TCM. AIM OF REVIEW: In this study, a strategy based on system pharmacology was constructed to uncover the multi-target regulation and compatibility mechanism of GQD on the Wnt signaling pathways. MATERIAL AND METHODS: The pharmacological network of GQD was constructed by TCMSP, DAVID, Uniprote database. The cell growth inhibitory effects of puerarin (PUE), wogonin (WOG), berberine (BER), and glycyrrhetinic acid (GLY) on SW480 cells were assessed using CCK-8 assay. The multi-target regulation and compatibility mechanism of combination PUE with GLY were examined by RNA-seq, HPLC-QQQ/MS, qRT- PCR and Western blot analysis. RESULTS: Network pharmacology analysis indicated that PUE, WOG, BER and GLY were the active components in GQD and had a synergistic effect on the targets of the Wnt signaling pathway. Additionally, pharmacological experiments revealed that WOG, BER, and GLY inhibited activity of colorectal cancer (CRC) cell lines SW480 cells, and that PUE only exhibited effective antitumour activity when combined with GLY. CTNNB1, CCND1 and SMAD4 were identified as synergistic targets inhibited by PUE-GLY. Moreover, PUE-GLY could influence the Wnt signaling pathway by upregulating GSK3B and downregulating CTNNB1 synergistically. It also showed that GLY could effectively increase the intracellular content of PUE based on HPLC-QQQ/MS analysis, and this process was achieved by influencing the targets of the membrane's pathway, such as cell adhesion molecules, focal adhesion, and tight junctions. CONCLUSION: GLY was revealed a multi-target mechanism, which could downregulate CTNNB1 as the active component and intervene in membrane proteins (CDH1, CADM1, ITGB2, ICAM1, ITGA1) as 'guide' in the formulae. Moreover, the mechanism of synergistic antitumour action of PUE (the active component of Monarch drug) and GLY (the active component of Guide drug) on the Wnt signaling pathway was explored systematically. It was a promising breakthrough for elucidating the scientific connotation of the compatibility of TCM formulae and provide a valuable and practicable methodology for clarifying the mechanisms of TCM.

[Applicability analysis and evaluation of aglycones in single-pass intestinal perfusion technique based on PBPK model].

Single-pass intestinal perfusion( SPIP) is the common carrier of biopharmaceutics classification system( BCS) to study compound permeability. With the application and deepening study of BCS in the field of traditional Chinese medicine( TCM),SPIP model is becoming more and more common to study the intestinal absorption of TCM ingredients. Based on the limitations of the SPIP model in some researches on TCM permeability,it was speculated in this study that aglycone may be more suitable than the glycoside to study the intestinal absorption problem by using SPIP model. Furthermore,applicability of aglycone components was analyzed and evaluated. In this study,with quercetin,daidzein,formononetin,genistein and glycyrrhetinic acid used as research objects,the quantitative study of SPIP was used to evaluate the intestinal permeability of these aglycones and to predict the effective permeability coefficient( Peff) and absorption fraction( Fa) in human body. By combining studies comparison and analysis on multiple permeability research methods and prediction of human body absorption of aglycones in physiological-based pharmacokinetic models,this paper can further illustrate that the SPIP model is a good tool for studying the permeability of aglycones and predicting human absorption,which can provide data foundation and theoretical reference for researches on SPIP technique and BCS in intestinal absorption of TCM ingredients.

[Formation and development of Dao-di herbs "Long" medicines].

Gansu province,which spans the Yangtze river,is in the upper reaches of the Yellow river and located at the intersection of the Qinghai-Tibet plateau,the Inner Mongolia plateau and the Loess plateau. All of these areas are highly respected by doctors of all ages as they have enriched the resources of traditional Chinese medicines. In the interaction between the heavens and the earth,the interaction between the people and the future has been passed down to the present. As one of the abbreviations of Gansu province, " Long" is not only the symbol and representative of the Gansu region,but also the symbol of the authentic medicinal materials in Gansu. This paper sorts out the evolution of the name " Long" medicines,the development status and development limitations of " Long" medicines. It is believed that although the production areas of authentic medicinal materials in Gansu have changed in different historical periods,the core varieties have been used ever since. Today,with the great development of the Chinese medicine industry,Gansu province pays attention to the limitations of the current regional and technological competitiveness in the province,and gives full play to its own advantages,which can help the " Long" medicines stand out among the medicinal materials. Furthermore,it lays the foundation for the development of the industry and the application of high quality Chinese herbal medicines in clinical practice.