Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

This study explored the anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship-integrated molecular docking. High performance liquid chromatography(HPLC) fingerprints of Trichosanthis Semen and its shell and kernel were established. Prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice in the low-and high-dose(5, 30 g·kg~(-1), respectively) Trichosanthis Semen, the shell, and kernel groups were determined as the coagulation markers. The spectrum-effect relationship and anticoagulant material basis of Trichosanthis Semen and its shell and kernel were analyzed with mean value calculation method of Deng's correlation degree(MATLAB) and the common effective component cluster was obtained. Then the common targets of the component cluster and coagulation were retrieved from TCMSP, Swiss-TargetPrediction, GenCLiP3, GeneCards, and DAVID, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The main anticoagulant molecular mechanism of the component cluster was verified by SYBYL-X 2.1.1. The spectrum-effect relationship of Trichosanthis Semen and its shell and kernel was in positive correlation with the dosage. The contribution of each component to anticoagulation was not the same, suggesting that the material basis for anticoagulation was different, but they have common effective components(i.e. common material basis), such as adenine(peak 3), uracil(peak 4), hypoxanthine(peak 6), xanthine(peak 9), and adenosine(peak 11). Network pharmacology showed that these components can act on multiple target proteins such as NOS3, KDR, and PTGS2, and exert anticoagulant effect through multiple pathways such as VEGF signaling pathway. They involved the biological functions such as proteolysis, cell component such as cytosol, and molecular functions. The results of molecular docking showed that the binding free energy of these components with NOS3(PDB ID: 1 D0 C), KDR(PDB ID: 5 AMN), and PTGS2(PDB ID: 4 COX) was ≤-5 kJ·mol~(-1), and the docking conformations were stable. Spectrum-effect relationship-integrated molecular docking can be used for the optimization, virtual screening, and verification of complex chemical and biological information of Chinese medicine. Trichosanthis Semen and its shell and kernel have the common material basis for anticoagulation and they exert the anticoagulant through multiple targets and pathways.
Animals ; Anticoagulants/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Gene Ontology ; Mice ; Molecular Docking Simulation ; Semen

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA_1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA_1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.
Aged ; Blood Pressure ; China/epidemiology* ; Cholesterol, LDL/therapeutic use* ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/drug therapy* ; Glycated Hemoglobin A/analysis* ; Humans ; Male ; Middle Aged

The Chinese Pharmacopoeia began to apply fingerprints (specific chromatogram) to quality control of traditional Chinese medicine in its 2010 edition, and in its 2015 and 2020 editions, new fingerprints (specific chromatogram) were added for improvement of the Pharmacopoeia-based national standards for drugs. This review analyzes the traditional Chinese medicine fingerprints (specific chromatogram) in Chinese Pharmacopoeia (2010-2020) in terms of the number of varieties listed, application of fingerprints (specific chromatogram), selection of evaluation method, determination method, the selection of extraction or preparation solvents of the test samples. With the expansion of the application of fingerprints (specific chromatogram), the evaluation indicators are constantly improving. The future development of the fingerprints (specific chromatogram) is also discussed in light of the selection of appropriate extraction or preparation solvents to obtain effective substances, which is the basis for the establishment of the fingerprints; multiple fingerprints for one drug based on different functional indications or basic sources, which expands the application of the fingerprints; addition of technical guidelines for traditional Chinese medicine fingerprints to standardize the use of the fingerprints; and the regular revision, update and application expansion of the fingerprints to ensure its essential role in quality control of traditional Chinese medicine.
China ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Quality Control ; Solvents

OBJECTIVE: To screen the effective antioxidant components in Trichosanthes extract based on the mean value of Deng's correlation degree and assess the antioxidant activity of the identified components. METHOD: High-performance liquid chromatography (HPLC) was used to obtain the fingerprints of Trichosanthes extract, and the clearance rates of DPPH · and O₂^-· by 3, 9 and 27 mg/mL Trichosanthes extract were determined. The antioxidant spectrum effect of Trichosanthes extract was analyzed by calculating the mean value of Deng's correlation degree to screen the effective antioxidant component group. According to the contents of each known components in the antioxidant effective component group, mixed solutions of the components were prepared and tested for their clearance rates of DPPH · and O₂^-·. RESULTS: The 36 common peaks in HPLC fingerprints of Trichosanthes extract showed different degrees of correlation with DPPH · and O₂^-· clearance. The common peaks with a correlation degree greater than the median value included peaks 21, 36, 8, 31, 14, 5, 27, 2, 24, 15, 18, 33, 22, 34, 35, 19, 28 and 25. The 5 components, namely kaempferol (peak 36), isoquercitrin (peak 8), luteolin (peak 31), rutin (peak 5) and apigenin (peak 35), were tentatively identified to constitute the effective antioxidant component group with a mass ratio 3∶2∶2∶ 1∶1 in Trichosanthes extract. The prepared mixed solutions of antioxidant effective component group (6.12, 2.04, and 0.68 μg/mL) showed clearance rates of DPPH · of 65.4%, 64.0% and 61.0%, and clearance rates of O₂^-· of 12.9%, 9.5% and 8.3%, respectively. CONCLUSION We identified the material basis for the antioxidant activity of Trichosanthes and screened the antioxidant effective component group in Trichosanthes extract.
Antioxidants/pharmacology* ; Chromatography, High Pressure Liquid/methods* ; Luteolin ; Plant Extracts/pharmacology* ; Trichosanthes/chemistry*

Objective To investigate the role of dual-layer detector energy spectral CT in resting myocardial perfusion imaging for patients with normal coronary artery. Methods One hundred and fifty-six patients with suspected coronary heart disease underwent dual-layer detector energy spectral CT coronary angiography,and resting myocardial perfusion imaging was performed for 28 patients with normal coronary artery.According to American Heart Association's 17-segmentmodel,the iodine density and effective atomic number(Z
Computed Tomography Angiography ; Coronary Angiography ; Coronary Vessels/diagnostic imaging* ; Humans ; Myocardial Perfusion Imaging ; Tomography, X-Ray Computed

To screen the antithrombotic effective components group of Trichosanthes extract, and to verify its pharmacodynamics and analyze its mechanism, the HPLC fingerprint of Trichosanthes extract (0.09, 0.45, 0.9 g·kg^-1) was established, and the pharmacodynamic indexes of antithrombosis in rats with aspirin (0.01 g·kg^-1) as positive control group were determined (the animals used in this experiment were approved by the Medical Ethics Committee of Wannan Medical College). The antithrombotic spectrum-activity relationship of Trichosanthes extract was studied and the effective antithrombotic ingredients group was screened by grey relational analysis. The monomer compound mixed solution (0.006, 0.03, 0.06 g·kg^-1) was prepared according to the content of each component in the active component group, and the pharmacodynamics and action mechanism were studied to verify the correctness of the spectrum-effect relationship. The correlation between the 22 components of Trichosanthes extract and antithrombotic efficacy was different and showed dose-effect relationship. Cytosine, uracil, guanine, hypoxanthine, xanthine, adenine, guanosine, and adenosine are the main antithrombotic components of Trichosanthes extract. The ratio of cytosine, uracil, guanine, hypoxanthine, xanthine, adenine, guanosine and adenosine was 3∶12∶10∶5∶2∶8∶13∶14. Compared with the model group, the thrombus dry weight of each effective components group could be effectively reduced (P<0.01 or P<0.05), but there was no significant difference between each effective components group and the Trichosanthes extract group. Compared with the model group, the TXB₂ content in group (0.06 g·kg^-1, 0.03 g·kg^-1) could be effectively reduced (P<0.01 or P<0.05), and the content of 6-keto-PGF_1α could be increased in each group (P<0.01), and the TXB₂/6-keto-PGF_1α tended to be normal and showed a dose-effect relationship. The effect was better than that in the Trichosanthes extract group (0.45 g·kg^-1) (P<0.01). The effective ingredients group has a good antithrombotic effect, its mechanism is to inhibit platelet aggregation and improve vascular endothelial function.

Network pharmacology and rat ischemia-reperfusion injury (MIRI) model was used to analyze the mechanism of cardiac protection by Trichosanthes. The animal experiments were approved by the Medical Ethics Committee of Wannan Medical College. Compounds were screened by TCMSP database and TCM Database@ Taiwan according to oral bioavailability (OB > 30%) and drug like activity (DL > 0.18). The PDBID value of the compound (Z'-score < 0.5) was obtained in DRAR-CPI database and converted into a target protein by UniProt database. Human genes of target proteins were identified using the term " myocardial ischemia reperfusion injury" as the keyword through the CoolGeN database. GOTERM_BP _ DIRECT enrichment analysis of target proteins related to MIRI and KEGG PATHWAY annotation analysis were performed using the DAVID database. The component-target protein-signal pathway network was constructed using Giphi0.9.2 software. The expression of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins in MIRI rats pretreated with Trichosanthes (0.2, 1.0 and 2.0 g·kg^-1) was analyzed by Western blot with compound Danshen (85.05 mg·kg^-1) as a positive control. Network pharmacology found that 12 compounds, including schottenol in Trichosanthes, synergistically inhibit MIRI through multiple targets or biological pathways, involving target proteins such as extracellular regulated protein kinase 2 (ERK2), c-jun-N-terminal kinase-1 (JNK1) and p38MAPK in MAPK signaling pathways. Western blot results showed that phosphorylation of ERK1/2 was dose-dependently up-regulated in MIRI rats pretreated with Trichosanthes, while the level of p38MAPK or JNK1 phosphorylation was down-regulated in a dose-dependent manner. Compared with the control group, phosphorylation of ERK1/2, JNK1 and p38MAPK protein showed significant difference in medium and high dose groups (1.0 and 2.0 g·kg^-1) (P<0.01). Therefore, Trichosanthes could play an anti-MIRI role by regulating phosphorylation of ERK1/2, JNK1 and p38MAPK proteins in rats. In conclusion, the targets and pathways of Trichosanthes on anti-MIRI were revealed by network pharmacology and verified in rat MIRI model, providing the scientific basis for further study on the mechanism of Trichosanthes for cardiac protection.

To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats. The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot) and the Database for Annotation,Visualization,and Integrated Discovery(DAVID) were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin. The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) and cyclic adenosine monophosphate(c AMP) in rat thrombotic model were studied. Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway. After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF) signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.
6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Aspirin ; pharmacology ; Cyclic AMP ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fruit ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rats ; Signal Transduction ; Thrombosis ; drug therapy ; Thromboxane B2 ; metabolism ; Trichosanthes ; chemistry

OBJECTIVETo investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism.

METHODSC57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice.

RESULTSCompared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice.

CONCLUSIONSExendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.