Salvianolic acid A ameliorates AGEs-induced glomerular endothelial dysfunction and protects against diabetic nephropathy

OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

Inhibitory effect of baicalein on mice tremor induced by oxotremorine and mechanisms

OBJECTIVE To investigate the anti-tremor effect and mechanism of baicalein on oxotremorine-induced muscle tremor in mice.METHODS The acute model of muscular tremor was induced by intraperitoneal injection of oxotremorine,and the latency,duration and frequency of muscle tremor in mice were measured immediately;the saliva of mice was measured to reflect the correlation between tremor and peripheral nerve function;the aim of this study was to determine the content of MDA and the activity of GSH-PX,and to investigate the anti-oxidation of mice with tremor model.The activity of acetylcholinesterase(AchE)and acetylcholine transferase(ChA T)can indirectly reflect the level of acetylcholine in the brain.The level of monoamine neurotransmitters in brain tissue was determined by high performance liquid chromatography(HPLC-ECD).RESULTS The animals in the model group appeared obvious tremoring,salivating and erecting and other symptoms.Compared to the model group,there was no obvious inhibitory effect on the administration of each dose.After 7,14,21 and 28 d of continuous administration,the latency,duration and tremor frequency of tremor mice were significantly shortened,the levels of acetylcholine were significantly decreased,the changes of DOPAC and DA neurotransmitters in the brain of model group were recovered,regulate the dynamic balance of acetylcholine and dopamine in the brain.CONCLUSION Long-term administration can improve the tremor behavior of mice,the mechanismmay be related to the regulation of neurotransmittersin brain.

Pinocembrin inhibits angiotensinⅡ-induced vasoconstriction in a Ca^(2+)-dependent and Ca^(2+)-independent manner through blocking AT_1R in the rat aorta

OBJECTIVE To investigate the vasorelaxant effect of pinocembrin(5,7-dihydroxyflavanone),one of the main flavonoids in propolis,on angiotensinⅡ(AngⅡ)induced vasoconstriction and the molecular mechanism of action.METHODS The isometric vascular tone was measured in thoracic aortic rings from SD rat,and the effects of pinocembrin on the single dose and concentration cumulative response curves of AngⅡ were recorded.The binding of pinocembrin to the angiotensin type 1 receptor(AT1R)was studied by using molecule docking analysis.Intracellular[Ca2+]([Ca2+]i)was measured with Fura2/AM in VSMCs.The phosphorylation levels of myosin light chain 2(MLC2)and myosin phosphatase target unit 1(MYPT1),and protein level of Rho kinase 1(ROCK1)in the rat aortic rings were detected by Western blotting.RESULTS Pinocembrin was observed to inhibit AngⅡ-induced vasoconstriction in rat aortic rings with either intact or denuded endothelium.In endothelium-denuded tissues,pinocembrin(pD′2 4.28±0.15)counteracted the contractions evoked by cumulative concentrations of AngⅡ.In a docking model,pinocembrin showed effective binding at the active site of AT1R.Pinocembrin was shown to inhibit both AngⅡ-induced Ca2+ release from internal stores and Ca2+ influx.Moreover,the increase in the phosphorylation of MLC2 and MYPT1,and the increased protein level of ROCK1 induced by AngⅡ was blocked by pinocembrin.CONCLUSION Pinocembrin inhibits AngⅡ-induced rat aortic ring contraction in a Ca2+-dependent and Ca2+-independent manner via blocking AT1R.

Curcumin,from health product to medicine

Curcumin is the principal curcuminoid of the rhizomes of Curcuma longa(turmeric,Jiang Huang),which has more than 6000 years of application history in India and other Asian countries.At present,curcumin is sold as an herbal supplement,cosmetics ingredient,food flavoring,and food coloring.In China curcumin is mainly used in food,while in western countries it has been regarded as a health care product and is contained in the British Pharmacopoeia(2017),United States Pharmacopeia(40)and European Pharmacopoeia(8.7th ed.).Curcumin has been proved to have multiple pharmacology effects including anti-fibrosis,anti-tumor,anti-inflammation effects and so on.As its broad biological activities,it is applicated in a lot of diseases such as hyperlipidemia,infection and cancer.Among them,the anti-cancer effect of curcumin is the most attractive.In the treatment of cancer and related diseases,curcumin has been tested in phase I and II clinical trials in several research centers across the world and has been approved by the U.S.FDA into the phase III clinical trial.It has been listed as the third generation of cancer chemoprevention agent by the U.S.National Cancer Institute.Curcumin has been proved to inhibit the proliferation of a variety of tumor cells through regulating a variety of tran.scription factors(NF-κB,AP-1,etc),mitogen-activated protein kinase(MAPK),growth factor receptor ki.nase(PDGFR,VEGFR,etc) and cyclooxygenase.It plays an important role in the cell cycle and further to inhibit proliferation.Curcumin can also inhibit the migration of tumor cells by activating caspase and in.ducing tumor cell apoptosis.However,curcumin still needs researches to confirm its effects and mecha.nisms and find its exact indications.There is still a long way to go to make curcumin better applied in clinical practice in the further.

Salvianolic acid A attenuates vascular remodeling in pulmonary arterial hypertension rats induced by monocrotaline

OBJECTIVE Salvianolic acid A(SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge) and exhibits many pharmaco.logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats.However,whether SAA improves vascular remodeling induced by pulmonary arterial hypertension(PAH) remains unknown.In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg^(-1)).The rats were orally treated with either SAA(0.3,1,3 mg·kg^(-1)·d^(-1)) or a positive con.trol Bosentan(30 mg·kg^(-1)·d^(-1)) for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab.normalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in.jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge.netic protein type Ⅱ receptor(BMPR Ⅱ) and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa.tients at high risk of PAH.

Increased life-span of Drosophila melanogaster by Flavonoids from Scutellariabaicalensis Georgi induced by hydrogen peroxide

Objective： To explore the effects and mechanisms of flavonoids from Scutellaria baicalensis Georgi in hydrogenperoxide （H2O2） induced Drosophila melanogaster model. Method： H2O2 induced Drosophila melanogaster agingmodel was used to study the effects of flavonoids from Scutellaria baicalensis Georgi. Secondly, the effects ofbaicalein and wogonin on mRNA expressions were examined. Results： Our results found that baicalein andwogonin could extend the life-spans of H2O2 induced Drosophila melanogaster aging model via increased mRNAexpressions of superoxide dismutase catalase and rosy. Conclusion： Baicalein and wogonin could extend life-spansof H2O2 induced Drosophila melanogaster aging model through increasing mRNA expressions of superoxidedismutase, catalase and rosy.

Xiao-Xu-Ming decoction extract regulates differentially expressed proteins in the hippocampus after chronic cerebral hypoperfusion

Xiao-Xu-Ming decoction has been widely used to treat stroke and sequelae of stroke. We have previously shown that the active fractions of Xiao-Xu-Ming decoction attenuate cerebral ischemic injury. However, the global protein profile and signaling conduction pathways regulated by Xiao-Xu-Ming decoction are still unclear. This study established a two-vessel occlusion rat model by bilateral common carotid artery occlusion. Rats were intragastrically administered 50 or 150 mg/kg Xiao-Xu-Ming decoction for 4 consecutive weeks. Learning and memory abilities were measured with Morris water maze. Motor ability was detected with prehensile test. Coordination ability was examined using the inclined screen test. Neuronal plasticity was observed by immunofluorescent staining. Differentially expressed proteins of rat hippocampus were analyzed by label-free quantitative proteomics. Real time-polymerase chain reaction and western blot assay were used to identify the changes in proteins. Results showed that Xiao-Xu-Ming decoction dramatically alleviated learning and memory deficits, and motor and coordination dysfunction, and increased the expression of microtubule-associated protein 2. Xiao-Xu-Ming decoction extract remarkably decreased 13 upregulated proteins and increased 39 downregulated proteins. The regulated proteins were mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process. The signaling pathways were mainly involved in ubiquitin mediated proteolysis and the phosphatidylinositol signaling system. Furthermore, there was an interaction among Rab2 a, Ptpn1, Ppm1 e, Cdk18, Gorasp2, Eps15, Capza2, Syngap1 and Mt-nd1. Protein analyses confirmed the changes in expression of MTND1. The current findings provide new insights into the molecular mechanisms of Xiao-Xu-Ming decoction extract's effects on chronic cerebral hypoperfusion.

Ramulus Cinnamomi extract attenuates neuroinflammatory responses via downregulating TLR4/MyD88 signaling pathway in BV2 cells

Ramulus Cinnamomi （RC）, a traditional Chinese herb, has been used to attenuate inflammatory responses. The purpose of this study was to investigate the effect of RC extract on lipopolysaccharide （LPS）-induced neuroinflammation in BV2 microglial cells and the underlying mechanisms involved. BV2 cells were incubated with normal medium （control group）, LPS, LPS plus 30 pg/mL RC extract, or LPS plus 100 pg/mL RC extract. The BV2 cell morphology was observed under an optical microscope and cell viability was detected by MTT assay. Nitric oxide level in BV2 cells was detected using Griess regents, and the levels of interleukin-6, interleukin-1 β, and tumor necrosis factor u in BV2 cells were determined by ELISA. The expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 proteins were detected by western blot assay. Compared with the LPS group, both 30 and 100 μg/mL RC extract had no significant effect on the viability of BV2 cells. The levels of nitric oxide, interleukin-6, interleukin-1β and tumor necrosis factor ct in BV2 cells were all significantly increased after LPS induction, and the levels were significantly reversed after treatment with 30 and 100 μg/mL RC extract. Furthermore, RC extract significantly inhibited the protein expression levels of cyclooxygenase-2, Toll-like receptor 4 and myeloid differentiation factor 88 in LPS-induced BV2 cells. Our findings suggest that RC extract alleviates neuroinflammation by downregulating the TLR4/MyD88 signaling pathway.

Research advances in antiplatelet activation of water soluble compounds in Salvia miltiorrhiza

Platelets are fragments of cytoplasm that are released from the mature megakaryocyte of the bone marrow.The main function of platelets is coagulation and hemostasis.Platelets play a central role in formation of pathological thrombosis.Many ischemic diseases are caused by excessive activa.tion of platelets,which can lead to thrombosis and death.Salvia miltiorrhiza Bunge,the dry roots and rhizomes of the Salvia miltiorrhiza plants,includes some water-soluble compounds,which play positive effects on diverse diseases such as neurodegenerative diseases,diabetic complications or cardiovas.cular diseases.In this paper,the components of the water-soluble in Salvia miltiorrhiza,as well as the applications in thrombotic diseases are summarized.The results show that water-soluble compounds include salvianolic acid A,salvianolic acid B,protocatechuic aldehyde,Danshensu,etc.The water-soluble compounds are applied to ischemic stroke,myocardial infarction and other diseases caused by thrombus.We also discussed the mechanisms of water-soluble compounds on the platelets based on our research results and the data obtained from references.The results indicate that water soluble compounds in Salvia miltiorrhiza play the antiplatelet and antithrombotic effects via different mechanisms,for example,salvianolic acid A inhibits platelet aggregation without promoting bleeding by increasing cAMP,inhibiting phosphoinositide 3-kinase(PI3K) and affecting GPCRs(G protein-coupled receptors) signaling path.ways;salvianolic acid B inhibit platelets as a P2Y12 antagonist and PDE inhibitor;Danshensu inhibits platelet activity may be related to inhibition of calcium influx.In conclusion,thrombotic diseases seriously affect human life and health.The existing antiplatelet drugs have some disadvantages.For example,aspirin may cause intracranial hemorrhage,and clopidogrel may play a slower role.Salvia miltiorrhiza as a traditional Chinese medicine has positive pharmacological activity and exerts antiplatelet aggrega.tion through different mechanisms.In the future,we will develop the new drugs which prevent and treat thrombotic diseases with the further study of the pharmacological effects and mechanisms of Salvia miltiorrhiza.

Research progress on pharmacological effect and mechanism of baicalein in Parkinson diseases

Parkinson disease(PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons(Lewy bodies),resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel.opment new drugs.Baicalein is a flavonoid isolated from traditional Chinese herb,Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxydopamine(6-OHDA) and promote the differentiation of PC12 cells through high throughput drug screen.ing at the cellularlevel.In vivo studies have shown that baicalein exerts significant therapeutic effect,particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory,we could consider neuroprotec.tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation.Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function,inhibition of collapse of mitochondrial membrane potential,increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia,as well as the production of cathepsin B and cytokines.Additionally,promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu) and gamma-aminobutyric acid(GABA).Overall,baica.lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody.namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.

Comparison of preventive and therapeutic effect on cardio-cerebral ischemic disease between salvianolic acids and aspirin

Aspirin(AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun.dred million,but many persons were died from interned bleeding.We found salvianolic acids(salvianolic acid B 57%,salvianolic acid A 1%,rosmarinic acid,35%,SA) was much better than AS in preventing in.cidence of cardio-cerebral ischemic disease,and may avoid hemorrhage risk in clinical application.The research are summary briefly as follows:(1) both AS and AS have same anti-platelet aggregation ef.fect,but their mechanism is different.AS inhibited both TXA2 and PGI2,SA inhibited TXA2 only;(2) For established thrombosis,SA could dissolved it,AS showed no effect.The thrombolytic mechanism of SA has been elucidated.(3) In SHRSP rats,the incidence of stroke and death rate in SA group was distinct less that of AS group;(4) In MCAO rats,SA and Sal B decreased stroke index and neural im.pairment.AS showed no such ability;(5) There is microcirculatory disturbance in cardio-cerebral ischemic disease.SA could improve circulatory disturbance induced by LPS,adrenaline,ROS and I/r.there is no any paper reported AS could have beneficial effect on above mentioned microcirculatory dis.turbance models;(6) Hyperlipidemia is an independent risk factor for cardio-cerebral vascular disease.SA could significant hypolipidemic effect which is similar to that of statins(atovastin and simvastin) and ten times stronger than omega-3.AS has no inhibitory effect on hyperlipidemia.(7) Thereis overproduc.tion of ROS induced by ischemic/reperfusion in cardio-cererbal vascular disease.SA showed more ro.bust,anti-oxidant capacity than VitC,Vit E,melatonin,edalavone and resveratrol,etc.SA is one of the most powerful anti-oxidant in the world so far.(8) According to literatures,1/3 patients who take AS for long time will have hemorrhage,we found in normal rats and mice(coagulating and hemodynamics)SA had no apparent effect on coagulation system and this property of SA was confirmed in clinic trial with hundred thousand cases;(9) As well known,neurodegenerative disease are divided into acute and chronic neurodegenerative disease,and both have similar pathogenesis.We proved that SA could inhibit Aβ aggregation and fiber formation,inhibit tau hyperphosphorylation induced by OA and p25/CDK5,as well as increase neurogenesis and angiogenesis.More importantly,SA showed not only pre.ventive effect on cardio-cerebral vascular diseases.SA has been finished clinical trial phase I-IV for treatment of stroke.The therapeutic effect of SA is characterized by inducing multi-target effect and in.hibit pathogenesis of early,middle and late stage of stroke.SA as anti-stroke new drug was approved by the state food and drug administration of China in 2011.

Purity and Uncertainty Study of CRM Betulin by DSC

Betulin(BE)can be obtained from many plants,such as those belonging Betulaceae family,and pharmacological investigations showed its notable biological properties and good potential for food and pharmaceutical development.We investigated the homogeneity,stability,purity,and uncertainty of a newly certified reference material(CRM)of BE.The certified purity value for the CRM of BE was 99.56%with an extended uncertainty of 0.07%(k=2,P=0.95),as determined by differential scanning calorimetry(DSC).In this study,DSC was used for the first time for purity determination of BE.Given its high accuracy,precision,and reproducibility,DSC can be used as an alternative technique for purity determination of CRMs in the pharmaceutical and food industry.

Saffron： a potential immunological adjuvant in anti-tumor therapy

A large and increasing number of patients in the world use medicinal plants and herbs for health purposes.Especially,chemoprevention using readily available natural substances from vege.tables,fruits,herbs and spices is one of the significantly important approaches for cancer prevention in the present era.Saffron is native to Iran and now recorded in "Chinese Pharmacopoeia" as a widely used Chinese medicine with good safety.Other than several useful pharmacological effects such as anticonvulsant,antidepressant,anti-inflammation,saffron and its active components(crocin,crocetin and safranal) have been shown to induce apoptosis in several tumor cell lines and mouse tumors with beneficial properties including radical scavenging,anti-mutagenic and immuno-modulating effects.In addition,saffron was reported good potential to alleviate the toxicity ofcisplatin,including the nephrotox.icity.However,the application of these components in the clinic has been limited due poor clinical trials data.This review aimed to provide a brief overview on clinical evaluation for anti-tumor potential and current molecule mechanism of saffron based on recent literature data.

Research advances in cardiovascular protective effects of flavonoids

Flavonoids are a large family of bioactive compounds widely found in foods and plants.Mang studies have proven the preventive and therapeutic effects of flavonoids in cardiovascular disease.Flavonoids has a wide range of pharmacological effects,including antioxidant,anti-inflammatory,vaso.dilation,avoiding the thrombus formation,improving endothelial function,modifying lipid levels and regulating blood lipids through different mechanisms of action.The cardiovascular protective mechanism of flavo.noids are the enzymes that inhibit the production of oxygen derived free radicals,inhibition of lipid peroxida.tion and inflammatory factor,down-regulation of epoxy synthase activity and the activation of AMPK and nuclear factor kappa B signaling pathway.In this review article we review and summarize the so far acquired knowledge of the most important mechanisms of action of flavonoids,to provide theoretical basis for the research and development of the active monomers in flavonoid and compound preparations.

Up-regulation of Fas Ligand Expression by Sirtuin 1 in both Flow-restricted Vessels and Serum-stimulated Vascular Smooth Muscle Cells

Objective To study the role of sirtuin 1 （SIRT1） in Fas ligand （FasL） expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell （VSMC） lysate. Smooth muscle cell （SMC）-specific human SIRT1 transgenic （Tg） C57BL/6 mice and their littermate wild-type （WT） controls underwent complete carotid artery ligation （ligation groups） or the ligation-excluded operation （sham groups）. The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 （SIRT1H363Y）, and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation （P〈0.001） and VSMCs treated with serum （P〈0.05 at the transcriptional level, P〈0.001 at the protein level）. No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL （P〈0.001）. The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 （P〈0.001）, while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 （P〈0.001）. Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.

Effect of Guizhi Fuling capsule and its extracts on human breast cancer cells proliferation

OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.

Xiao-Xu-Ming decoction protects against chronic cerebral ischemia injury in rats and profile of differentially expression proteins analysis in hippocampus

OBJECTIVE Vascular dementia(VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia.2-Vessels occlusion(2-VO) has been widely used as a model of VD.Xiao-Xu-Ming decoction,a well-known traditional Chinese medicine prescrip.tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats.METHODS After XXM treatment,rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody.Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics.RESULTS XXM significantly alleviated 2-VOinduced learning and memory deficits,motor ability dysfunction,and neuronal plasticity injury in rats.The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process,intracellular signaling cascade process,and protein catabolic process,etc.The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system.CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.

Withaferin A exerts anti-tumor effects in glioblastoma cells by arresting cell cycle at G_2/M phase

Glioblastoma(GBM) is the most common,malignant,and lethal primary brain tumor in adults.Up to now,there is no effective drug for GBM.Withaferin A(WFA) is mainly derived from Indian Winter cherry.It has been traditionally used in ayurvedic medicine.WFA has wide range of pharmaco.logical activities including cardioprotective,anti-inflammatory,immuno-modulatory properties.Recently,WFA was reported to inhibit the growth of many cancer cells;however,the precise molecular mecha.nisms of its anti-cancer activities in GBM remain unclear.Here,we found that treatment of WFA in U251 and U87-MG glioma cells inhibited the cell proliferation,released the cellular LDH,decreased the DNA synthesis,and inhibited the migration,invasion,and colony formation of cells.WFA also in.creased the apoptotic rate of cells,decreased the mitochondrial membrane potential,arrested cell cy.cle at G_2/M,inhibited the activity of caspase 3/7,and increased the protein expression of cleaved-cas.pase 3,cleaved PARP in U251 and U87-MG cells.In addition,cell apoptosis induced by WFA was as.sociated with increasing level of Bim,Bad,P21,P53 and decreasing the level of p-CDK1,cyclin A and B.It was also shown that cell apoptosis induced by WFA was associated with P38 signal pathway.These results demonstrated that WFA induced mitochondrial dependent apoptosis in glioblastoma cells which was associated with arresting the cell cycle at G_2/M phase by P38 pathway.Taken together,our findings suggest that WFA might be a promising chemotherapy drug in the treatment of GBM.

Study,application and communication of traditional medicine among the Belt and Road Countries

Most medicines used in the ancient people were the natural raw products,and most of them were discovered during the life.As the differences of the geography,climate and living habits among the different regions,various medicines were used for treatment of diseases in local people.The communication of medicines made a lot of benefits for people living in different regions.Communication of medicines promote the application of medicines and natural resources.As early as 2000 year ago,the ancient Chinese people had sent a lot of medicines to many countries among the Belt and Road during their visiting to these countries.The medicines were the main contents for communication besides of the silk and porcelain.These medicines has been used for treatment of diseases for local people till now.On the Belt and Road,many spices,fruits,seeds produced in different regions were spread among the countries.Most of them were planted and produced in China.But the important events were the application of these special products,such as spices,fruits and seeds used as medicines under the guidance of traditional Chinese medical theory.These drugs have played major roles in the treatment of diseases and development of traditional Chinese medicine.Communication of the medicines,including the medical theory and drugs,improved the medical standards in China.For example,ancient Persian medicine had a significant impact on the use of traditional Chinese medicine in the prescription application.And also,the medicines made important contributions to the health of people in the countries on the Belt and Road.Now,the science and techniques have been developed.Many principles and understandings are different from the ancient people.However,the medicines developed in the countries on the Belt and Road still used for the health of human beings.To research the ancient medicines by the modern techniques and through co-operation will greatly contribute to human healthand promote the social progress and economic development of the countries on the Belt and Road.