Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs / 中国中药杂志

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS / 中国天然药物

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats / 中国中药杂志

This study is to explore the effect of Qingfei Paidu Decoction(QPD) on the host metabolism and gut microbiome of rats with metabolomics and 16 S rDNA sequencing. Based on 16 S rDNA sequencing of gut microbiome and metabolomics(GC-MS and LC-MS/MS), we systematically studied the serum metabolites profile and gut microbiota composition of rats treated with QPD for continued 5 days by oral gavage. A total of 23 and 43 differential metabolites were identified based on QPD with GC-MS and LC-MS/MS, respectively. The involved metabolic pathways of these differential metabolites included glycerophospholipid metabolism, linoleic acid metabolism, TCA cycle and pyruvate metabolism. Meanwhile, we found that QPD significantly regulated the composition of gut microbiota in rats, such as enriched Romboutsia, Turicibacter, and Clostridium_sensu_stricto_1, and decreased norank_f_Lachnospiraceae. Our current study indicated that short-term intervention of QPD could significantly regulate the host metabolism and gut microbiota composition of rats dose-dependently, suggesting that the clinical efficacy of QPD may be related with the regulation on host metabolism and gut microbiome.

Characteristics of dental arch and basal bone in permanent dentition Angle Class Ⅱ malocclusion based on three-dimensional digital models / 中国组织工程研究

BACKGROUND:An orthodontist can gain all comprehensive data about the tooth and jaw based on a model measurement.With the development of CAD/CAM,a three-dimensional (3D) digital model shows more accurate information than a traditional model.OBJECTIVE:To explore the characteristics of dental arch and basal bone in permanent dentition Angle Class Ⅱ malocclusion based on 3D digital models.METHODS:Thirty cases of normal occlusionin permanent dentition were selected as control group,and 30 cases of Angel Ⅱ1 and 30 cases of Angel Ⅱ2 malocclusion were enrolled,respectively.Three kinds of 3D digital models were established using a 3shape R700 scanner and measured with Orthoanalyzer 2013.The data of individual normal occlusion and Angel Ⅱ1 and Angel Ⅱ2 data were analyzed statistically with SPSS 19.0 software respectively.Intergroup comparison was analyzed by the least significant difference test method.RESULTS AND CONCLUSION:Maxillary and mandibular dental arch length and maxillary dental arch width of front section (3-3) and middle section (4-4)/maxillary basal bone length and mandibular basal bone width of middle section (4-4):Ⅱ2 ＞ normal occlusion ＞ Ⅱ1 (P ＜ 0.05).Mandibular dental arch front width of section (3-3)/maxillary and mandibular basal bone length:normal occlusion ＞ Ⅱ1＞ Ⅱ2 (P ＜ 0.05).Maxillary dental arch width of behind section (6-6)/maxillary basal bone width of front section (3-3) and middle section (4-4)/mandibular basal bone width of front section (3-3):normal occlusion ＞ Ⅱ2 ＞ Ⅱ1 (P ＜ 0.05).The angle of tooth long axis and plane:there was significant difference in the Angel Ⅱ1,Ⅱ2 and normal occlusion (P ＜ 0.05).Maxillary posterior-teeth area (coronary):Ⅱ1 ＞ Ⅱ2 ＞ normal occlusion (P ＜ 0.05).Mandibular posterior-teeth area (coronary):Ⅱ2 ＞ normal occlusion ＞ Ⅱ1 (P＜ 0.05).The dental arch of Angel Ⅱ1 was narrow and long in shpape,and the dental arch of Angel Ⅱ2 was wide and short in shape.Sagittal discordant existed in the anterior of Angel Ⅱ1,such as lip-side incline of maxilla and mandible.Coronal discordant existed in the median and posteior of Angel Ⅱ1,such as palatine-side incline of the maxillary dental arch,and buccal-side incline of the mandible.Sagittal discordant existed in the anterior of Angel Ⅱ2,e.g.lingual-side incline of the maxilla and mandible.No discordant existed in the posterior section of Angel Ⅱ2.