Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal/chemistry* ; Research ; Drug Discovery ; China

Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Mammalian catechol-O-methyltransferases(COMT)are an important class of conjugative enzymes,which play a key role in the metabolism and inactivation of catechol neurotransmitters,catechol es-trogens and a wide range of endobiotics and xenobiotics that bear the catechol group.Currently,COMT inhibitors are used in combination with levodopa for the treatment of Parkinson's disease in clinical practice.The crucial role of COMT in human health has raised great interest in the development of more practical assays for highly selective and sensitive detection of COMT activity in real samples,as well as for rapid screening and characterization of COMT inhibitors as drug candidates.This review summarizes recent advances in analytical methodologies for sensing COMT activity and their applications.Several lists of biochemical assays for measuring COMT activity,including the probe substrates,along with their analytical conditions and kinetic parameters,are presented.Finally,the challenges and future perspec-tives in the field,such as visualization of COMT activity in vivo and in situ,are highlighted.Collectively,this review article overviews the practical assays for measuring COMT activities in complex biological samples,which will strongly facilitate the investigations on the relevance of COMT to human diseases and promote the discovery of COMT inhibitors via high-throughput screening.

This paper aims to systematically analyze the peptides and proteins from Asini Corii Colla(ACC) through shotgun proteomics. After high-pH reversed-phase fractionation, the proteins and peptides in the hydrolysate of ACC were further separated by nano LC-Q-Exactive-MS/MS under the following conditions: Thermo Scientific EASY column(100 μm×2 cm, 5 μm, C_(18)) as precolumn, Thermo Scientific EASY column(75 μm×100 mm, 3 μm, C_(18)) for solid phase extraction, gradient elution with 0.1% formic acid in water(mobile phase A) and 84% acetonitrile in water containing 0.1% formic acid(mobile phase B), and MS in positive ion mode. Based on Uniprot_Equus caballus, MS data, and literature, 2 291 peptides were identified from ACC by MaxQuant, with 255 Maillard reactions(AML, CML, CEL)-modified peptides identified for the first time. Through alignment, the peptides were found to belong to 678 equine proteins. In conclusion, the combination of nano LC-Q-Exactive-MS/MS and shotgun proteomics achieved rapid and accurate identification of the proteins and peptides in ACC, which provides the key information and new insights for further investigation of chemicals and effective substances in ACC.
Animals ; Chromatography, Liquid ; Horses ; Peptides ; Proteins ; Proteomics ; Tandem Mass Spectrometry

Huosu Yangwei (HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD, AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.
Animals ; Biomarkers ; China ; Drugs, Chinese Herbal ; Mice ; Network Pharmacology ; Stomach Neoplasms/genetics*

Objective:To determine the prognostic values of clinical and laboratory features at the time of presentation on renal survival of patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis (MPO-ANCA-GN).Methods:A total of 172 patients with MPO-ANCA-GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2005 to December 2018 were enrolled. The baseline clinical characteristics and renal biopsy pathological data were analyzed, and the renal prognosis was followed up. The clinical and pathological characteristics of different renal prognosis in all patients and 112 patients who underwent renal biopsy were analyzed, and the related factors affecting renal survival were further discussed.Results:Among these 172 patients, 81 were males and 91 were females. The median serum creatinine at diagnosis was 343.7(174.2, 606.6) μmol/L and the median estimated glomerular filtration rate (eGFR) was 15.81(7.61, 38.04) ml·min -1·(1.73 m 2) -1. In total, 76 patients (44.2%) received initial renal replacement therapy (RRT). During a median follow-up duration of 20(3, 60) months, 73 patients (42.4%) progressed to end-stage renal disease (ESRD) and required dialysis, including 6 (8.2%) patients who entered RRT during follow-up and 67 (91.8%) patients who received RRT at the beginning. Among the 112 patients who underwent renal biopsy, the proportion of patients who progressed to ESRD in the sclerotic group was the highest (15/25, 60.0%). The baseline serum creatinine level ( P<0.001), urine red blood cell count ( P=0.012) and the proportion of glomerular sclerosis ( P=0.002) in the non-dialysis dependent group were significantly lower than those in the dialysis dependent group, while the levels of eGFR ( P<0.001), serum albumin ( P=0.002) and hemoglobin ( P<0.001) were higher than those of the dialysis-dependent group. Kaplan-Meier survival analysis showed that the renal survival rate of the focal group was the highest ( χ2=19.488, P<0.001, log-rank test), while the renal survival rate of the sclerotic group was significantly lower than that of the crescentic group ( χ2=5.655, P=0.017); higher levels of serum creatinine (>320 μmol/L, χ2=77.229, P<0.001) and urine red blood cell count (>300 cells/μl, χ2=8.511, P=0.004), lower levels of rheumatoid factor (<20 IU/ml, χ2=8.610, P=0.003), serum albumin (<30 g/L, χ2=11.060, P=0.001) and hemoglobin (<90 g/L, χ2=21.921, P<0.001) were associated with lower renal survival rate; in terms of treatment, the renal survival rate of the glucocorticoids plus mycophenolate mofetil group was significantly higher than that of the glucocorticoids plus cyclophosphamide ( χ2=5.056, P=0.025) or the glucocorticoids alone group ( χ2=16.459, P<0.001). Multivariate Cox regression showed that baseline serum creatinine >320 μmol/L ( HR=8.803, 95% CI 3.087-25.106, P<0.001) and serum albumin <30 g/L ( HR=2.566, 95% CI 1.246-5.281, P=0.011) were the related factors affecting renal survival. Conclusion:Serum creatinine and albumin levels of MPO-ANCA-GN patients at diagnosis may be the related factors that affect the patient's renal prognosis.

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.
Carboxylesterase/metabolism* ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions

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.
Administration, Oral ; Alkaloids/analysis* ; Animals ; COVID-19 ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacokinetics* ; Flavonoids/analysis* ; Mice ; SARS-CoV-2 ; Saponins/analysis* ; Triterpenes/analysis*

Cephalotaxus is the only genus of Cephalotaxaceae family, and its natural resources are declining due to habitat fragmentation, excessive exploitation and destruction. In many areas of China, folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison, many of which are cancer. Not only among Han people, but also among minority ethnic groups, Cephalotaxus is used to treat various diseases, e.g., cough, internal bleeding and cancer in Miao medicine, bruises, rheumatism and pain in Yao medicine, and ascariasis, hookworm disease, scrofula in She medicine, etc. Medicinal values of some Cephalotaxus species and compounds are acknowledged officially. However, there is a lack of comprehensive review summarizing the ethnomedicinal knowledge of Cephalotaxus, relevant medicinal phytometabolites and their bioactivities. The research progresses in ethnopharmacology, chemodiversity, and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here. Knowledge gaps are pinpointed and future research directions are suggested. Classic medicinal books, folk medicine books, herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus (Sanjianshan in Chinese). The relevant data about ethnobotany, phytochemistry, and pharmacology were collected as comprehensively as possible from online databases including Scopus, NCBI PubMed, Bing Scholar, and China National Knowledge Infrastructure (CNKI). "Cephalotaxus", and the respective species name were used as keywords in database search. The obtained articles of the past six decades were collated and analyzed. Four Cephalotaxus species are listed in the official medicinal book in China. They are used as ethnomedicines by many ethnic groups such as Miao, Yao, Dong, She and Han. Inspirations are obtained from traditional applications, and Cephalotaxus phytometabolites are developed into anticancer reagents. Cephalotaxine-type alkaloids, homoerythrina-type alkaloids and homoharringtonine (HHT) are abundant in Cephalotaxus, e.g., C. lanceolata, C. fortunei var. alpina, C. griffithii, and C. hainanensis, etc. New methods of alkaloid analysis and purification are continuously developed and applied. Diterpenoids, sesquiterpenoids, flavonoids, lignans, phenolics, and other components are also identified and isolated in various Cephalotaxus species. Alkaloids such as HHT, terpenoids and other compounds have anticancer activities against multiple types of human cancer. Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities, immunomodulatory activity, antimicrobial activity and nematotoxicity, antihyperglycemic effect, and bone effect, etc. Drug metabolism and pharmacokinetic studies of Cephalotaxus are increasing. We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms, so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs. Transcriptomics, genomics, metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants. We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.