Pharmacologic mechanisms mining and prediction of Xiaoer Qixing Cha Formulae in the treatment of infantile functional dyspepsia based on chemical analysis by UPLC-QTOF/MS and interactive network pharmacology

目的:对小儿七星茶的主要化学成分进行解析和鉴定,并探讨其治疗小儿消化不良的作用机制。方法:采用UPLC-QTOF/MS技术对小儿七星茶进行测定分析。通过数据库搜索化学成分相关靶点和疾病相关靶点,并筛选出小儿七星茶对应的疾病治疗靶点。运用Cytoscape软件进行网络建立和分析,同时将成分和靶点根据药材来源进行归类,通过靶点数目分布验证组方的“君、臣、佐、使”配伍规律。运用ClueGo进行GO生物功能分析和KEGG通路富集,进一步预测小儿七星茶发挥药效的作用机制。结果:通过解析得到5 3 个化合物,筛选出疾病相关靶点6 3 个,其中AKT1、FOS、SLC6A4、COM T和5-H T受体是重要靶点,能调节碳水化合物消化吸收、5-H T代谢和cA M P等信号通路。结果表明,小儿七星茶能通过干预脑肠轴相关的靶点和通路发挥治疗作用。结论:本研究为小儿七星茶的深入研究提供了实验和理论基础,为中药复方的药效学机制研究提供了科学依据。

Protective Effects of Traditional Tibetan Medicine Zuo-Mu-A Decoction(佐木阿汤)on the Blood Parameters and Myocardium of High Altitude Polycythemia Model Rats

Objective: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction(佐木阿汤, ZMAD) on the blood parameters and myocardium of high altitude polycythemia(HAPC) model rats. Methods: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L.(RRL) and ZMAD groups(10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL(20 mL/kg) and ZMAD(7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2’-deoxyguanosine(8-OHd G) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. Results: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHd G levels, and also increased the erythrocyte deformation index(P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. Conclusion: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

Efficacy of Shouzhangshen(Rhizoma Gymnadeniae Crassinervidis)extract against acute high altitude hypoxia-induced brain injury in mice

OBJECTIVE:To evaluate the protective effect of Shouzhangshen(Rhizoma Gymnadeniae Crassinervidis)extract against acute high altitude hypoxia-induced brain injury in mice.METHODS:Sixty C57BL/6J mice were selected and assigned to six groups(n=10):normal control group,low-pressure hypoxia group,positive control group(dexamethasone 500 mg/kg),and three groups treated with Shouzhangshen extract(250,500,and 750 mg/kg,respectively).The Morris water maze test was performed to evaluate alterations in spatial learning and memory deficits.Nissl staining was performed to detect Nissl bodies and neuron damage.Hypoxia-inducible factor(HIF)-1α,interleukin(IL)-1β,tumor necrosis factor(TNF)-α,vascular endothelial growth factor(VEGF),and malondialdehyde(MDA)expression in brain tissue and serum,as well as superoxide dismutase(SOD)and glutathione(GSH)activity in brain tissues were measured by enzyme-linked immunosorbent assays,quantitative real-time-polymerase chain reaction and western blots.RESULTS:The Morris water maze test results showed that Shouzhangshen extract can significantly reduce the latency and swimming distance to escape onto a visible platform,increase neuron density and hierarchy and the number of pyramidal neurons,and decrease the expression of HIF-1α,IL-1β,TNF-α,and VEGF mRNAs and proteins in both brain tissue and serum(P<0.05).Furthermore,significantly lower MDA expression and higher GSH activity were detected in the three groups treated with Shouzhangshen compared with the low-pressure hypoxia group(P<0.05).However,no significant alteration was observed for SOD activity(P>0.05).CONCLUSION:Our findings suggest that Shouzhangshen extract may have a significant effect on acute high altitude hypoxia-induced brain injury in mice.

Nitrogen-doped Carbon Dots: Application of Hg Ions Detection in Rannasangpei

Nitrogen-doped carbon dots(N-CDs) were hydrothermally synthesized by folic acid, which revealed excited wavelengtli-dependent blue emission and the specific recognition ofHg ions by fluorescence quenching. A wide range response and a fitted linear relationsliip for Hg ions detection were established to show that tliese blue-emission N-CDs achieved a satisfying Hg ions detection in Chinese traditional herb, Rannasaiigpei(RSNP). Tlie results from the N-CDs FL quenching gave the similar outcomes with those from ICP-OES measurement, which exhibited the possibility of the simple FL method of Hg ions detection by N-CDs in Chinese traditional herbs.

A new diterpenoid alkaloid isolated from Delphinium caeruleum

The present study was designed to determine the chemical constituents of Delphinium caeruleum Jacq. ex Camb.. The chemical constituents were isolated and purified by column chromatography with silica gel, ODS, and Sephadex LH-20. Their structures were elucidated by IR, MS, and NMR. Ten compounds were obtained and identified as caerudelphinine A(1), lycoctonine(2), talitine B(3), talitine A(4), talitine C(5), tatsienine-V(6), d-magnoflorine(7), 2-trimethyl-ammonio-3-(3-indolyl) propionate(8), vakhmatine(9), and delatisine(10). Compound 1 was a new lycoctonine-type C19-diterpenoid alkaloid, and compounds 4-10 were isolated from this plant for the first time.

Synthesis and biological evaluation of new peroxo-bridged diosgenin derivatives

Objective： In order to find lead compound with anti-HBV activity from peroxo-bridged diosgenin deriva- tives obtained with Eosin Y as the photosensitizer. Method： Eosin Y was used as the photosensitizer to activate the oxygen in the air to synthesize novel diosgenin derivatives with peroxo-bridge. The structures of synthesized compounds were identified by NMR and HR-MS. Their cytotoxicity and antihepatitis B activity were evaluated via MTS assay and ELISA method, respectively. Results： Six diosgenin derivatives were synthesized, three of which contained peroxo-bridge, and their structures were confirmed by spectroscopy. It showed that 5a,8a-peroxo-6-alkenyl-diosgenin （7） could suppress the production of HBsAg on transfected HepG2.2.15 cells at low-toxic concentration and the in- hibition rate on HepG2.2.15 cells was 18.28% at 12.50 μg/mL, better than that of 3TC （7.30% at 12.50 μg/mL） and others. Conclusion： Due to its lower cytotoxicity and potential anti-hepatitis B activity, compound 7 could be developed as the promising candidate of anti-hepatitis B drug. It also indicated that the peroxo-bridged derivatives had potential biological values for developing clinical agents.

Dual-property blue and red emission carbon dots for Fe(Ⅲ)ions detection and cellular imaging

The excitation wavelength-dependent and-independent emissions are two crucial fluorescent properties of carbon dots(CDs).However,CDs reported till date exhibit only one of these properties,which limits their practical applications.Herein,dual-property carbon dots(DCDs)with both the excitation wavelength-dependent and-independent emissions were synthesized via a facile onestep solvothermal method using 4-(2-pyridylazo)-resorcinol as the carbon precursor.The multi-functional applications of the resulting DCDs were also evaluated.The asprepared DCDs exhibited not only excellent monodispersity,high photostability,and storage stability,but also low toxicity,good biocompatibility,and cellular bioimaging capability.In addition,the DCDs exhibited excitation-dependent emission photoluminescence under low excitation wavelengths.The DCDs exhibited good Fe3+detection by quenching the blue emission fluorescence and showed a relatively low Fe3+detection limit of 0.067 lmol·L-1 based on three times signal-to-noise criteria(R2=0.99).Furthermore,the DCDs showed excitation-independent emission at low excitation wavelengths and exhibited red emission at about 598 nm to avoid damage to the body.These results demonstrate the excellent bioimaging properties of the DCDs.Owing to their dual PL properties,the as-prepared DCDs exhibited multi-functional applications:Fe3+detection and A549 cell bioimaging.These results will be helpful in developing novel CDs for applications in various fields.