OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stre...OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress(CSDS)-induced depressive-like behaviors and its related mechanism.METHODS AND RE⁃SULTS The daily oral administration of Rb1(35 and 70 mg·kg-1)and imipramine(15 mg·kg-1)for 28 d significantly reversed the social avoidance behavior,anhedonia,and behavioral despair via CSDS exposure,as demonstrated by the consid⁃erable elevation in the time in the zone in social interaction test and consumption of sucrose solu⁃tion in sucrose preference test and decrease of immobility time in forced swim test.Moreover,Rb1 obviously restored the CSDS-induced decrease of BDNF-signaling pathway and hippo⁃campal neurogenesis.Rb1 significantly increased the hippocampal levels of ERK,AKT,and CREB phosphorylation and increased the number of DCX+cells in DG.Importantly,the antidepres⁃sant effects of Rb1 were completely blocked in mice by using K252a(the nonselective tyrosine kinase B inhibitor).CONCLUSION Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression,and its effects was facilitated by enhancing the BDNF signaling cas⁃cade and up-regulation of hippocampal neuro⁃genesis.展开更多
AIM: To study the effect of ginsenoside Rgl and Rhl on the anti - tumor activity of dendritic cells (DC). METHODS: Effect of Rgl and Rhl on the production of IL- 12 p40 protein was detected by ELISA, and the IL- 12 p4...AIM: To study the effect of ginsenoside Rgl and Rhl on the anti - tumor activity of dendritic cells (DC). METHODS: Effect of Rgl and Rhl on the production of IL- 12 p40 protein was detected by ELISA, and the IL- 12 p40 mRNA level of DC was monitored by RT- PCR. Anti - tumor activity of DC- LPAK was detemnined by neutral red staining assay. RESULTS: The results of ELLSA showed that Rgl and Rhl significantly enhanced the production of IL- 12 p40 of DC. Rgl at 1 mg/L and Rhl at 100 mg/L upregulated the IL- 12 p40 mRNA level. Rgl and Rhl enhanced the anti - tumor ability of DC, induced lyrnphokine and PHA activated killer (DC-LPAK) on human papillate tumor cell line. Each dose of Rgl can obviously accelerate the eytotoxity to L929 at the E: T ratio of 5 : 1 (P<0.05,0.01 ), while only Rhl 10 mg/L enhanced the eytotoxity ability of DC- LPAK (P < 0.05). CONCLUSION: Rgl and Rhl enhanced the production of IL-12 p40. This effect may be mediated by the increase in the mRNA level. As a result, Rg1 and Rhl oromote the ability of DC to stimulate the cytotoxitie aetieity of DC - LPAK.展开更多
OBJECTIVE Ginsenoside Rg1(Rg1),a purified compound from Panax ginseng,has been well documented to be effective against ischemia/reperfusion(I/R) neurotoxicity.However,the underlying mechanism is stil obscure.METHODS T...OBJECTIVE Ginsenoside Rg1(Rg1),a purified compound from Panax ginseng,has been well documented to be effective against ischemia/reperfusion(I/R) neurotoxicity.However,the underlying mechanism is stil obscure.METHODS The anti-I/R effect of Rg1 were investigated in vitro and in vivo,and the dynamics of nuclear accumulation and the transcriptional activity of NF-E2-related factor 2(Nrf2) determined by Western blotting and Dual Luciferase Reporter Assay,respectively.Nrf2 siRNA was employed to investigate Nrf2′s role in the protective effect of Rg1 against I/R.Furthermore,the role of miR-144,which could regulate post-translational Nrf2 levels,was investigated in the anti-I/R effect of Rg1 by injection of AAV-hypoxia-inducible factor miR-144-shRNA in the predicted ischemic penumbra.RESULTS It was found that the anti-I/R effect of Rg1 was related to its anti-oxidative capacity,which is mainly regulated by the Nrf2/antioxidant response element(ARE) pathway.Further study suggested that Rg1 contributes to the enhancement of the Nrf2/ARE pathway,as manifested by increasing the dynamic peak content of Nrf2,which prolonged the maintenance stage,and promoting the expression of ARE-target genes after oxygen glucose deprivation/reperfusion(OGD/R) in PC12 cells.Nrf2-siRNA application significantly reduced these changes.Furthermore,the enhancement of the Nrf2/ARE pathway by Rg1 was independent of disassociation from Keap1;rather it was a result of posttranslational regulations.It was found that Rg1 significantly reduced the expression of miR-144,which down-regulates Nrf2 production by targeting its 3′-untranslated region,after OGD/R.Knockdown of Nrf2 showed no effect on the expression of miR-144,indicating that miR-144 is an upstream regulator of Nrf2.Moreover,direct binding between Nrf2 and miR-144 in the PC12 cells was identified.Application of anti-miR-144 significantly reduced Rg1′s anti-OGD/R capacity.Final y,the role of miR-144 in Rg1′ s anti-I/R effect was tested by inhibiting miR-144 in the predicted ischemic penumbra when hypoxia-inducible-factor was activated.The results showed that loss of miR-144 abolished the anti-I/R effect of Rg1,which included reduced infarct volume,improved neurological scores,attenuated oxidative impairment,as well as activation of the Nrf2/ARE pathway.CONCLUSION Oxidative stress after I/R is alleviated by Rg1 through inhibition of miR-144 activity and subsequent promotion of the Nrf2/ARE pathway at the post-translational level.展开更多
Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macol...Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rgl is the most pharmacological active one. Based on prior experi- mental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rgl is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the under- lying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g · kg^-1 alcohol 1 h after treated with Rgl （ 10, 20 and 40 mg · kg^-1） or dexamethasone （ 1 mg · kg^-1） for 9 consecutive days. Biochemi- cal analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rgl treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but re- stored in Rgl-treated groups. Overproductive inflammatory cytokines were also suppressed by Rgl in alcohol-intoxi- cated mouse livers. In addition, changes of GR related NF-KB pathway, including phospho-IKB-ot, were also mod- ulated to normal levels. Conclusion This study demonstrates that Rgl might promote GR mediating the repression of NF-KB and inhibit the inflammatory reactions in alcoholic hepatitis.展开更多
Aim To investigate the effects of general ginsenoside on the pulmonary fibrosis in mice. Methods All the animals were divided into the sham operation group, model control group and the groups administered with gen- er...Aim To investigate the effects of general ginsenoside on the pulmonary fibrosis in mice. Methods All the animals were divided into the sham operation group, model control group and the groups administered with gen- eral ginsenoside （40, 80, 160 mg · kg^-1） and prednisone （5 mg · kg^-1） group. The mice pulmonary fibrosis was induced by bleomycin （BLM 5 mg · kg^-1） and general ginsenoside （40, 80 and 160 mg · kg^-1） and prednisone （ 5 mg · kg^- 1 ） were given the day after surgery for 28consecutive days. The pulmonary fibrosis induced by bleomy- cin （BLM 5 mg · kg^-1） was evidenced by the pulmonary index, histopathology, and by the expression of alpha smooth muscle actin （oL-SMA）. Results Compared with that of the sham operation control, the pulmonary index were remarkably increased, Pathological examination demonstrated that BLM administration induced focal fibrotie lesions （ Alveolitis and pulmonary fibrosis） in mice lungs, and the expression of α-SMA mRNA was elevated for sev- eral time in the model control. However, compared with model control, general ginsenoside and prednisone admin- istrated could cause significantly decreases in the pulmonary index, the degree and extent of alveolitis and fibrosis had different degree of ease, reduce the elevated α-SMA mRNA expression. Conclusion General ginsenoside in- duced protection against the pulmonary fibrosis induced by bleomycin in mice.展开更多
OBJECTIVE To evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/probenecid(MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms.METHODS M...OBJECTIVE To evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/probenecid(MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms.METHODS Male C57BL/6 mice were randomly assigned to six groups.One hour prior to MPTP/p injection,GroupⅢ-Ⅵmice received 10 mg·kg^(-1),20 mg·kg^(-1),or 40 mg·kg^(-1) Rg1 or 3 mg·kg^(-1) selegiline,respectively,orally from D(-3) to D49.GroupⅠ-Ⅱmice received solvent water.Subsequently,GroupⅡ-Ⅵmice received by injection MPTP-HCl(25 mg·kg^(-1) bw dissolved in0.9%saline,sc)on a 40-d schedule at intervals of 4 d between consecutive doses in combination with an adjuvant drug,probenecid(250 mg·kg^(-1) bw in 0.03 mL of DMSO,ip);GroupⅠmice were injected with saline and probenecid.Behavioral performance was assessed in the open field test,pole test and rotarod test.Neurotransmitters in the striatum were detected using HPLC.Protein levels were measured by Western blot.Pathological characteristics were examined by immunohistochemistry.Ultrastructure changes were observed by electron microscopy.RESULTS Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality,behavior defects,loss of dopamine neurons and abnormal ultrastructure changes in the SNpc.Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties.Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-1b(IL^(-1)b)in the SNpc.Rg1 also al eviated the unusual MPTP induced increase in oligomeric,phosphorylated and disease-related a-synuclein in the SNpc.CONCLUSION Rg1 protects dopaminergic neurons,most likely by reducing aberrant a-synuclein-mediated neuroinflammation,and holds promise for Parkinson disease therapeutics.展开更多
OBJECTIVE To evaluate whether ginsenoside Rb1 has antiepileptic effects on pen⁃tylenetetrazole(PTZ)-induced epileptic mice via intranasal therapeutic administration.METHODS Rb1 monoclonal antibody was used to observe ...OBJECTIVE To evaluate whether ginsenoside Rb1 has antiepileptic effects on pen⁃tylenetetrazole(PTZ)-induced epileptic mice via intranasal therapeutic administration.METHODS Rb1 monoclonal antibody was used to observe the distribution of Rb120 mg·kg-1 in mouse brain tissues under different administration routes and to explore the feasibility of intranasal Rb1.PTZ was injected intraperitoneally into healthy ICR mice every 48 hours to construct a tonic-clonic epileptic model.Then Rb120 or 40 mg·kg-1 or valproate 300 mg·kg-1 or saline was administered intranasally for 30 d,and PTZ was continued every five days to imitate occa⁃sional convulsions in the clinic.Racine scale(RCS)and wireless electroencephalogram(EEG)monitoring were used to assess the presence and severity of seizure.Immunofluorescence(IF)was performed after drug treatment to evalu⁃ate the effect of Rb1 on brain neuron,microglia and astrocyte in epileptic mice.RESULTS Rb1 had specific binding with anti-Rb1 in the brain under different administration routes,and intrana⁃sal Rb1 was able to enter the brain and play a therapeutic role(P<0.01).PTZ-injured mice pre⁃sented body mass loss,higher seizure stage and shorter seizure latency.At the same time,epilep⁃tic waves,mainly spikes,were detected by wire⁃less EEG.Compared with PTZ group,intranasal Rb1 increased mice weight(P<0.01)and seizure latency(P<0.05),reduced seizure stage(P<0.01)and EEG spikes.In addition,Rb1 significantly reduced neuron loss(P<0.01)indicated by NeuN staining and decreased the number of acti⁃vated microglia(P<0.01)indicated by Iba-1 staining in the cortex and CA1 area of hippocam⁃pus.Moreover,Rb1 reduced the decrease of GLT-1 and GS expression(P<0.05)induced by PTZ.CONCLUTION Intranasal Rb1 has anti-epi⁃leptic effects on PTZ mice.Moreover,Intranasal Rb1 affects the functions of neurons,astrocytes and microglia through regulating the expression of GLT and GS in astrocytes,which may be related to its anti-epileptic effect.展开更多
OBJECTIVE Ginsenoside metabolite compound K(CK)is a degradation product of ginsenoside in the intestine by bacteria.The anti-inflammatory and immunomodulatory activities of CK have been reported.This study investigate...OBJECTIVE Ginsenoside metabolite compound K(CK)is a degradation product of ginsenoside in the intestine by bacteria.The anti-inflammatory and immunomodulatory activities of CK have been reported.This study investigated whether CK exerted its immunoregulatory effect through modulation of dendritic cells(DCs)function.METHODS In vivo,severity of collegen-induced arthritis(CIA),T cells and DCs subsets,phenotype of DC were assayed by flow cytometry,CCL19 and CCL21 level in lymph nodes assayed by ELISA.In vitro,bone marrow-derived DCs from normal mice were matured with lipopolysaccharide and treated with CK for 48 h.In vivo,bone marrow-derived DCs were generated from CIA mice before and 2 weeks into CK treatment.DCs were analyzed for migration,phenotype and T-cell stimulatory capacity.RESULTS CK alleviated the severity of CIA,decreased pD Cs and mo-DCs,increased na?ve T cells in CIA mice lymph nodes,and suppressed CCL21 expression in lymph nodes.CK suppressed DCs migration induced by CCL21 and T cells-stimulatory capability of DC,down-regulated LPS-induced expression of CD80,CD86,MHCII and CCR7 on DCs.CONCLUSION This study elucidated the novel immunomodulatory property of CK via impairing function of DCs in priming T cells activation.These results provide an interesting novel insight into the potential mechanism by which CK contribute to the restoration of immunoregulation in autoimmune conditions.展开更多
OBJECTIVE To investigate the transcriptomic details on the biosynthetic pathways in different parts of the Panax notoginseng and the pharmacological activity of the saponins extracted from the flower(FS)on vascular in...OBJECTIVE To investigate the transcriptomic details on the biosynthetic pathways in different parts of the Panax notoginseng and the pharmacological activity of the saponins extracted from the flower(FS)on vascular insufficiency conditions.METHODS RNA sequencing of three different Panax notoginseng tissues was performed using next generation DNA sequencing and differential gene expression was validated by real-time PCR.In order to determine pro-angiogenic and therapeutic effects of FS on myocardial infraction(MI),FS was examined on the endothelial cell migration assay,vascular insufficiency model in zebrafish and MI model in rats.RESULTS After assembling the high quality sequencing reads into 107 340 unigenes,biochemical pathways were predicted and 9 908 unigenes were assigned to 135 KEGG pathways.Among them,270 unigenes were identified to be involved in triterpene saponin biosynthesis as well as 350 and 342unigenes were predicted to encode cytochrome P450 sand glycosyltransferases,respectively.One unigene was annotated as CYP716A53v2,probably participates in the formation of protopanaxatriol from protopanaxadiol and the differential expression of this gene was confirmed by real-time PCR.In addition,the pharmacological evaluation demonstrate that FS significantly promoted vascular endothelial growth factor(VEGF)induced the migration of human umbilical vein endothelial cells(HUVECs)and partially restored defective intersegmental vessels in a chemically induced vascular insufficiency model of zebrafish larva.Moreover,the two week posttreatment of the rat MI model with FS(25-50mg·kg-1·d-1)induced approximately 3-fold upregulation of VEGF mRNA expression,with a concomitant increase in blood vessel density in the peri-infarct area of the heart by 50.7%,compared to 41.4%in the MI group.Furthermore,TUNEL analysis indicates a reduction in the mean apoptotic nuclei per field in peri-infarct myocardium upon FS treatment.CONCLUSION We have established a global transcriptome dataset for Panax notoginseng and provided additional genetic information for further genome-wide research and analyses.Candidate genes involved in ginsenoside biosynthesis,including putative cytochrome P450 sand glycosyltransferases were obtained.The transcriptomes in different plant tissues also provide invaluable resources for future study of the differences in physiological processes and secondary metabolites in different parts of P.notoginseng.And the significant pro-angiogenic effect of FS in multiple experimental models renders the purified saponin preparation as potential preventive and therapeutic agent for cardiovascular diseases yet to be developed.展开更多
OBJECTIVE To investigate the anti-arthritic effect and mechanism of action of ginsenoside Rb1 on adju⁃vant-induced arthritis(AIA)in rats.METHODS Male SD rats were received 0.1 mL injections of FCA(10 g·L^-1)emuls...OBJECTIVE To investigate the anti-arthritic effect and mechanism of action of ginsenoside Rb1 on adju⁃vant-induced arthritis(AIA)in rats.METHODS Male SD rats were received 0.1 mL injections of FCA(10 g·L^-1)emulsion into the right hind metatarsal foot pad for arthritis induction.After that,rats were randomly divided into six groups,namely control group,untreated group,dexamethasone(DEX,2.5 mg·kg^-1)group,low(5 mg·kg^-1),medium(10 mg·kg^-1)and high(20 mg·kg^-1)doses of ginsenoside Rb1 groups,and treated intraperitoneally at the above dosage once a day for 2 weeks.After treatment,paw swelling and arthritis indexes were evaluated,the thymus and spleen index were calculated as well.HE staining were used to observe the joint histopathology in rats.Rat ELISA kits were used to determinate the TNF-α,IL-1βand IL-6 levels.Western blotting were used to detect the related protein expression of NF-κB signaling pathway in the tissues of inflamed joints.RESULTS Rb1 significantly decreased the paw swelling and arthritis index,Compared with AIA group.HE staining results revealed that medium and high doses of Rb1 significantly reduced synovial inflammatory cell infiltration,synovial lining hyperplasia and bone destruction,compared with AIA group.Elisa results showed that Rb1 significantly decreased the TNF-α,IL-1β and IL-6 levels(P<0.05,P<0.01).Western blotting results revealed that the expression of p-IκB and p-P65 were significantly reduced in 20 mg·kg^-1 of Rb1 group,compared with AIA group(P<0.05,P<0.01).CONCIUSION Rb1 manifests therapeutic anti-inflammatory effects on rats with AIA,poten⁃tially through a mechanism of inhibiting activation of the NF-κB.展开更多
Panax Ginseng has been used for thousands of years in traditional Chinese medicine(TCM)as a tonic to improver stamina and vitality.Ginsenoside Rg1(Rg1),a saponin extracted from Panax ginseng,is considered one of the m...Panax Ginseng has been used for thousands of years in traditional Chinese medicine(TCM)as a tonic to improver stamina and vitality.Ginsenoside Rg1(Rg1),a saponin extracted from Panax ginseng,is considered one of the most potent pharmacological candidates among TCM.In various diseases related to nervous system,Rg1 has shown excellent pharmacological activities.①Stroke:Rg1 has been well documented to be effective against ischemic/reperfusion(I/R)neuronal injury.A systematic review and meta-analysis revealed a marked efficacy of Rg1 in experi⁃mental acute ischemic stroke,as manifested by its ability to reduce infract volume and improve neurological score.The protective effects of Rg1 were abolished by injecting of AAV-HIF-miR-144-shRNA into the predicted ischemic penumbra.②Depression:In addition,Rg1 showed antidepressive effects in chronic unpredictable mild stress(CUMS)model of depression and in gonadectomized(GDX)model of neuroendocrine disturbance.Rg1 displayed antidepressant activity through the modulation of HPA and HPG axis,markedly alleviated depression-like behavior in rats.Long-term Rg1 treat⁃ment of CUS-exposed rats also significantly prevented the decrease in dye diffusion and improved the ultrastructure of astrocyte gap junctions in the PFC.Rg1 upregulated Cx43 expression in PFC reduced by CUS exposure,indicating beneficial effects on the functional activity of gap junction channels in the brain.③Parkinson disease(PD):Oral treatment with Rg1 significantly attenuated high MPTP-induced mortality,behavior defects,loss of dopamine neurons and abnormal unltrastructure changes in SNpc.It regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as TNF-alpha and IL-1βin SNpc.Rg1 also alleviated the unusual MPTP-induced increase in oligomeric,phosphorylated and disease-relatedα-synuclein in SNpc.④Alzheimer disease(AD):Okadaic acid(OKA)intracerebroventricular injection induced memory impairment,including changes in the ability of orientation navigate,spatial probe and relearning memory in behavioral test of Morris water maze(MWM).OKA treated rats showed memory impair⁃ment including increasing of phospho-tau,decreasing of phospho-GSK3βand the formation ofβ-amyloid in special brain regions,which were reversed by Rg1.The possible neuroprotective mechanism might be that Rg1 decreases OKAinduced memory impairment through GSK3β/tau signaling pathway and/or attenuating Aβformation.Meanwhile,Rg1 activated ERK/MAPK pathway by CaMKIIα,and the activation of CREB was not only dependent on ERK induced by Rg1.Additionally,Rg1 inhibited microglial activation by suppressing Iba1 expression.Rg1 inhibited the inflammation mediated by LPS through suppressing NF-κB and MAPK pathway,which provided the explanation for its therapeutic ef⁃fect on neurodegenerative diseases.展开更多
OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(Lo...OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(LoVo)xenografts were treated with SMI 10 mL·kg^-1 daily for 1 or 8 d.Multidimensional PK profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.For PD studies,the tumor-bearing mice Intravital multi-photon imaging and CD31 immunofluorescence staining were used to evaluate the number of microves⁃sels and braches.Double staining of CD31 and α-SMA was performed to evaluate pericytes coverage ratios around vessels.ELISA was performed to determine the concentrations of VEGF and FGF in tumor tissues.For synergistic anti-tumor study,the tumor-bearing mice were treated with SMI 10 mL·kg^-1 daily,Rd 5 mg·kg^-1 daily with or without 5-FU 15 mg·kg^-1 every 3 d for 20 d.HPLC-MS/MS was used to determine the concentrations of 5-FU in plasma and tumor tissues.RESULTS SMI decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and improved vascular pericytes coverage(P<0.05).PK studies showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both,plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In fact,the proportion of Rd in the detectable components of SMI gradually increased in the following order:SMI formula(2.8%),plasma(16.0%),tumor tissues(34.3%),and TECs(40.3%).In vivo bioactivity results showed that Rd 5 mg·kg^-1 daily significantly decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and increased pericytes coverage(P<0.05)while Rd 0.5 mg·kg^-1 daily,Rb1 and Rg1 had no significant effect on them.Rd 5 mg·kg^-1 suppressed the expression of VEGF and FGF simultaneously.Rd 5 mg·kg^-1 enhanced the antitumor effect of 5-FU via increasing the distribution of 5-FU in tumor tissues(P<0.05)in xenograft mice.CONCLUSION Ginsenoside Rd may be the major bioactive anti-angiogenic constituent targeting TECs after SMI treatment.展开更多
OBJECTIVE Panax ginseng C.A.Meyer(ginseng)is a well-known medicinal plant worldwide and a key ingredient in many commercially-available health products.It is used as a tonic for invigoration and for tification in time...OBJECTIVE Panax ginseng C.A.Meyer(ginseng)is a well-known medicinal plant worldwide and a key ingredient in many commercially-available health products.It is used as a tonic for invigoration and for tification in times of fatigue and debility or declining capacity for work and concentration.Previous in-house study has surveyed over three hundred ginseng and ginseng products(including P.ginseng,P.quinquefolius,P.notoginseng,P.pseudoginseng)available in Singapore.This review presents an overview of the pharmacological activities and herb-drug interactions of P.ginseng and its ginsenosides.METHODS Literature searches of PubMed and ScienceDirect were done to identify pharmacological activities and herb-drug interactions of P.ginseng,its extracts and its chemical components,including ginsenosides.Studies of whole plant extracts include both White ginseng and Red ginseng.The studies for the pharmacological activities of whole plant extract were limited to those published from 2009 to 2015.There was no restriction on the time frame of other studies.Terms such as″P.ginseng″,″Ginsenosides″were searched.Studies found included in vitro assays,in vivo animal studies,human clinical trials as well as individual case reports.RESULTS A total of 112 studies were found on whole plant extracts and 257 studies on its individual components.Whole plant extracts of ginseng were found to possess over fifty different pharmacological activities,while its individual components exhibit parts of this spectrum.P.ginseng was found to interact with drugs such as 5-fluorouracil,irinotecan,mitomycin C,docetaxel,cisplatin,alcohol,midazolam,warfarin,phenelzine,raltegravir and imatinib.CONCLUSION P.ginseng and its components exhibit a wide range of pharmacological activities and interact with some drugs.There remain much opportunities for future research.展开更多
基金Ministry of Science and Tech⁃nology of China(2017ZX09301029)and Space Medical Experiment Project of China Manned Space Program(HYZHXM05003)。
文摘OBJECTIVE Ginsenoside Rb1(Rb1),an important bioactive ingredient of Panax ginseng,has potent neuroprotective effects.The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress(CSDS)-induced depressive-like behaviors and its related mechanism.METHODS AND RE⁃SULTS The daily oral administration of Rb1(35 and 70 mg·kg-1)and imipramine(15 mg·kg-1)for 28 d significantly reversed the social avoidance behavior,anhedonia,and behavioral despair via CSDS exposure,as demonstrated by the consid⁃erable elevation in the time in the zone in social interaction test and consumption of sucrose solu⁃tion in sucrose preference test and decrease of immobility time in forced swim test.Moreover,Rb1 obviously restored the CSDS-induced decrease of BDNF-signaling pathway and hippo⁃campal neurogenesis.Rb1 significantly increased the hippocampal levels of ERK,AKT,and CREB phosphorylation and increased the number of DCX+cells in DG.Importantly,the antidepres⁃sant effects of Rb1 were completely blocked in mice by using K252a(the nonselective tyrosine kinase B inhibitor).CONCLUSION Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression,and its effects was facilitated by enhancing the BDNF signaling cas⁃cade and up-regulation of hippocampal neuro⁃genesis.
文摘AIM: To study the effect of ginsenoside Rgl and Rhl on the anti - tumor activity of dendritic cells (DC). METHODS: Effect of Rgl and Rhl on the production of IL- 12 p40 protein was detected by ELISA, and the IL- 12 p40 mRNA level of DC was monitored by RT- PCR. Anti - tumor activity of DC- LPAK was detemnined by neutral red staining assay. RESULTS: The results of ELLSA showed that Rgl and Rhl significantly enhanced the production of IL- 12 p40 of DC. Rgl at 1 mg/L and Rhl at 100 mg/L upregulated the IL- 12 p40 mRNA level. Rgl and Rhl enhanced the anti - tumor ability of DC, induced lyrnphokine and PHA activated killer (DC-LPAK) on human papillate tumor cell line. Each dose of Rgl can obviously accelerate the eytotoxity to L929 at the E: T ratio of 5 : 1 (P<0.05,0.01 ), while only Rhl 10 mg/L enhanced the eytotoxity ability of DC- LPAK (P < 0.05). CONCLUSION: Rgl and Rhl enhanced the production of IL-12 p40. This effect may be mediated by the increase in the mRNA level. As a result, Rg1 and Rhl oromote the ability of DC to stimulate the cytotoxitie aetieity of DC - LPAK.
基金The project supported by National Natural Science Foundation of China(81603315 81730096+4 种基金 81373551 81730093U1402221)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-004)the Opening Program of Shanxi Key Laboratory of Chinese Medicine Encephalopathy(CME-OP-2017001)
文摘OBJECTIVE Ginsenoside Rg1(Rg1),a purified compound from Panax ginseng,has been well documented to be effective against ischemia/reperfusion(I/R) neurotoxicity.However,the underlying mechanism is stil obscure.METHODS The anti-I/R effect of Rg1 were investigated in vitro and in vivo,and the dynamics of nuclear accumulation and the transcriptional activity of NF-E2-related factor 2(Nrf2) determined by Western blotting and Dual Luciferase Reporter Assay,respectively.Nrf2 siRNA was employed to investigate Nrf2′s role in the protective effect of Rg1 against I/R.Furthermore,the role of miR-144,which could regulate post-translational Nrf2 levels,was investigated in the anti-I/R effect of Rg1 by injection of AAV-hypoxia-inducible factor miR-144-shRNA in the predicted ischemic penumbra.RESULTS It was found that the anti-I/R effect of Rg1 was related to its anti-oxidative capacity,which is mainly regulated by the Nrf2/antioxidant response element(ARE) pathway.Further study suggested that Rg1 contributes to the enhancement of the Nrf2/ARE pathway,as manifested by increasing the dynamic peak content of Nrf2,which prolonged the maintenance stage,and promoting the expression of ARE-target genes after oxygen glucose deprivation/reperfusion(OGD/R) in PC12 cells.Nrf2-siRNA application significantly reduced these changes.Furthermore,the enhancement of the Nrf2/ARE pathway by Rg1 was independent of disassociation from Keap1;rather it was a result of posttranslational regulations.It was found that Rg1 significantly reduced the expression of miR-144,which down-regulates Nrf2 production by targeting its 3′-untranslated region,after OGD/R.Knockdown of Nrf2 showed no effect on the expression of miR-144,indicating that miR-144 is an upstream regulator of Nrf2.Moreover,direct binding between Nrf2 and miR-144 in the PC12 cells was identified.Application of anti-miR-144 significantly reduced Rg1′s anti-OGD/R capacity.Final y,the role of miR-144 in Rg1′ s anti-I/R effect was tested by inhibiting miR-144 in the predicted ischemic penumbra when hypoxia-inducible-factor was activated.The results showed that loss of miR-144 abolished the anti-I/R effect of Rg1,which included reduced infarct volume,improved neurological scores,attenuated oxidative impairment,as well as activation of the Nrf2/ARE pathway.CONCLUSION Oxidative stress after I/R is alleviated by Rg1 through inhibition of miR-144 activity and subsequent promotion of the Nrf2/ARE pathway at the post-translational level.
文摘Aim Ginseng is the dried root of Panax ginseng C. A. Mayer. Since ancient times, ginseng has been used as one kind of treatment drug or tonic in China and even other eastern countries like Korea and Japan. Phar- macological active chemical ingredients and its extract of ginseng are a mixture of triterpenoid saponins, collectively called ginsenosides. Among them, ginsenoside Rgl is the most pharmacological active one. Based on prior experi- mental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rgl is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the under- lying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g · kg^-1 alcohol 1 h after treated with Rgl （ 10, 20 and 40 mg · kg^-1） or dexamethasone （ 1 mg · kg^-1） for 9 consecutive days. Biochemi- cal analyses were performed and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results According to our data, Rgl treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but re- stored in Rgl-treated groups. Overproductive inflammatory cytokines were also suppressed by Rgl in alcohol-intoxi- cated mouse livers. In addition, changes of GR related NF-KB pathway, including phospho-IKB-ot, were also mod- ulated to normal levels. Conclusion This study demonstrates that Rgl might promote GR mediating the repression of NF-KB and inhibit the inflammatory reactions in alcoholic hepatitis.
文摘Aim To investigate the effects of general ginsenoside on the pulmonary fibrosis in mice. Methods All the animals were divided into the sham operation group, model control group and the groups administered with gen- eral ginsenoside （40, 80, 160 mg · kg^-1） and prednisone （5 mg · kg^-1） group. The mice pulmonary fibrosis was induced by bleomycin （BLM 5 mg · kg^-1） and general ginsenoside （40, 80 and 160 mg · kg^-1） and prednisone （ 5 mg · kg^- 1 ） were given the day after surgery for 28consecutive days. The pulmonary fibrosis induced by bleomy- cin （BLM 5 mg · kg^-1） was evidenced by the pulmonary index, histopathology, and by the expression of alpha smooth muscle actin （oL-SMA）. Results Compared with that of the sham operation control, the pulmonary index were remarkably increased, Pathological examination demonstrated that BLM administration induced focal fibrotie lesions （ Alveolitis and pulmonary fibrosis） in mice lungs, and the expression of α-SMA mRNA was elevated for sev- eral time in the model control. However, compared with model control, general ginsenoside and prednisone admin- istrated could cause significantly decreases in the pulmonary index, the degree and extent of alveolitis and fibrosis had different degree of ease, reduce the elevated α-SMA mRNA expression. Conclusion General ginsenoside in- duced protection against the pulmonary fibrosis induced by bleomycin in mice.
基金supported by National Natural Science Foundation of China(81274122,81373997,U1402221,81573640,81273629)Beijing Natural Science Foundation(7131013)+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education of China(20121106130001)Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study(BZ0150)
文摘OBJECTIVE To evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/probenecid(MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms.METHODS Male C57BL/6 mice were randomly assigned to six groups.One hour prior to MPTP/p injection,GroupⅢ-Ⅵmice received 10 mg·kg^(-1),20 mg·kg^(-1),or 40 mg·kg^(-1) Rg1 or 3 mg·kg^(-1) selegiline,respectively,orally from D(-3) to D49.GroupⅠ-Ⅱmice received solvent water.Subsequently,GroupⅡ-Ⅵmice received by injection MPTP-HCl(25 mg·kg^(-1) bw dissolved in0.9%saline,sc)on a 40-d schedule at intervals of 4 d between consecutive doses in combination with an adjuvant drug,probenecid(250 mg·kg^(-1) bw in 0.03 mL of DMSO,ip);GroupⅠmice were injected with saline and probenecid.Behavioral performance was assessed in the open field test,pole test and rotarod test.Neurotransmitters in the striatum were detected using HPLC.Protein levels were measured by Western blot.Pathological characteristics were examined by immunohistochemistry.Ultrastructure changes were observed by electron microscopy.RESULTS Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality,behavior defects,loss of dopamine neurons and abnormal ultrastructure changes in the SNpc.Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties.Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-1b(IL^(-1)b)in the SNpc.Rg1 also al eviated the unusual MPTP induced increase in oligomeric,phosphorylated and disease-related a-synuclein in the SNpc.CONCLUSION Rg1 protects dopaminergic neurons,most likely by reducing aberrant a-synuclein-mediated neuroinflammation,and holds promise for Parkinson disease therapeutics.
文摘OBJECTIVE To evaluate whether ginsenoside Rb1 has antiepileptic effects on pen⁃tylenetetrazole(PTZ)-induced epileptic mice via intranasal therapeutic administration.METHODS Rb1 monoclonal antibody was used to observe the distribution of Rb120 mg·kg-1 in mouse brain tissues under different administration routes and to explore the feasibility of intranasal Rb1.PTZ was injected intraperitoneally into healthy ICR mice every 48 hours to construct a tonic-clonic epileptic model.Then Rb120 or 40 mg·kg-1 or valproate 300 mg·kg-1 or saline was administered intranasally for 30 d,and PTZ was continued every five days to imitate occa⁃sional convulsions in the clinic.Racine scale(RCS)and wireless electroencephalogram(EEG)monitoring were used to assess the presence and severity of seizure.Immunofluorescence(IF)was performed after drug treatment to evalu⁃ate the effect of Rb1 on brain neuron,microglia and astrocyte in epileptic mice.RESULTS Rb1 had specific binding with anti-Rb1 in the brain under different administration routes,and intrana⁃sal Rb1 was able to enter the brain and play a therapeutic role(P<0.01).PTZ-injured mice pre⁃sented body mass loss,higher seizure stage and shorter seizure latency.At the same time,epilep⁃tic waves,mainly spikes,were detected by wire⁃less EEG.Compared with PTZ group,intranasal Rb1 increased mice weight(P<0.01)and seizure latency(P<0.05),reduced seizure stage(P<0.01)and EEG spikes.In addition,Rb1 significantly reduced neuron loss(P<0.01)indicated by NeuN staining and decreased the number of acti⁃vated microglia(P<0.01)indicated by Iba-1 staining in the cortex and CA1 area of hippocam⁃pus.Moreover,Rb1 reduced the decrease of GLT-1 and GS expression(P<0.05)induced by PTZ.CONCLUTION Intranasal Rb1 has anti-epi⁃leptic effects on PTZ mice.Moreover,Intranasal Rb1 affects the functions of neurons,astrocytes and microglia through regulating the expression of GLT and GS in astrocytes,which may be related to its anti-epileptic effect.
基金supported by National Nature Science Foundation of China(81503084,81330081,31200675,and 81173075)
文摘OBJECTIVE Ginsenoside metabolite compound K(CK)is a degradation product of ginsenoside in the intestine by bacteria.The anti-inflammatory and immunomodulatory activities of CK have been reported.This study investigated whether CK exerted its immunoregulatory effect through modulation of dendritic cells(DCs)function.METHODS In vivo,severity of collegen-induced arthritis(CIA),T cells and DCs subsets,phenotype of DC were assayed by flow cytometry,CCL19 and CCL21 level in lymph nodes assayed by ELISA.In vitro,bone marrow-derived DCs from normal mice were matured with lipopolysaccharide and treated with CK for 48 h.In vivo,bone marrow-derived DCs were generated from CIA mice before and 2 weeks into CK treatment.DCs were analyzed for migration,phenotype and T-cell stimulatory capacity.RESULTS CK alleviated the severity of CIA,decreased pD Cs and mo-DCs,increased na?ve T cells in CIA mice lymph nodes,and suppressed CCL21 expression in lymph nodes.CK suppressed DCs migration induced by CCL21 and T cells-stimulatory capability of DC,down-regulated LPS-induced expression of CD80,CD86,MHCII and CCR7 on DCs.CONCLUSION This study elucidated the novel immunomodulatory property of CK via impairing function of DCs in priming T cells activation.These results provide an interesting novel insight into the potential mechanism by which CK contribute to the restoration of immunoregulation in autoimmune conditions.
基金The project supported by the Scheme B funding of the project′Establishment of the Centre for Microbial Genomics and Proteomics′and the Scheme D funding of the project′Enhancing the capabilities and strengthening the research personnel of CUHK in Bioinformatics′of the Focused Investment Scheme of The Chinese University of Hong Kongthe Overseas and Hong Kong,Macao Young Scholars Collaborative Research Fund by the Natural National Science Foundation of China(81328025)+1 种基金Science and Technology Development Fund of Macao SAR(058/2009and 078/2011/A3)Research Committee,University of Macao
文摘OBJECTIVE To investigate the transcriptomic details on the biosynthetic pathways in different parts of the Panax notoginseng and the pharmacological activity of the saponins extracted from the flower(FS)on vascular insufficiency conditions.METHODS RNA sequencing of three different Panax notoginseng tissues was performed using next generation DNA sequencing and differential gene expression was validated by real-time PCR.In order to determine pro-angiogenic and therapeutic effects of FS on myocardial infraction(MI),FS was examined on the endothelial cell migration assay,vascular insufficiency model in zebrafish and MI model in rats.RESULTS After assembling the high quality sequencing reads into 107 340 unigenes,biochemical pathways were predicted and 9 908 unigenes were assigned to 135 KEGG pathways.Among them,270 unigenes were identified to be involved in triterpene saponin biosynthesis as well as 350 and 342unigenes were predicted to encode cytochrome P450 sand glycosyltransferases,respectively.One unigene was annotated as CYP716A53v2,probably participates in the formation of protopanaxatriol from protopanaxadiol and the differential expression of this gene was confirmed by real-time PCR.In addition,the pharmacological evaluation demonstrate that FS significantly promoted vascular endothelial growth factor(VEGF)induced the migration of human umbilical vein endothelial cells(HUVECs)and partially restored defective intersegmental vessels in a chemically induced vascular insufficiency model of zebrafish larva.Moreover,the two week posttreatment of the rat MI model with FS(25-50mg·kg-1·d-1)induced approximately 3-fold upregulation of VEGF mRNA expression,with a concomitant increase in blood vessel density in the peri-infarct area of the heart by 50.7%,compared to 41.4%in the MI group.Furthermore,TUNEL analysis indicates a reduction in the mean apoptotic nuclei per field in peri-infarct myocardium upon FS treatment.CONCLUSION We have established a global transcriptome dataset for Panax notoginseng and provided additional genetic information for further genome-wide research and analyses.Candidate genes involved in ginsenoside biosynthesis,including putative cytochrome P450 sand glycosyltransferases were obtained.The transcriptomes in different plant tissues also provide invaluable resources for future study of the differences in physiological processes and secondary metabolites in different parts of P.notoginseng.And the significant pro-angiogenic effect of FS in multiple experimental models renders the purified saponin preparation as potential preventive and therapeutic agent for cardiovascular diseases yet to be developed.
文摘OBJECTIVE To investigate the anti-arthritic effect and mechanism of action of ginsenoside Rb1 on adju⁃vant-induced arthritis(AIA)in rats.METHODS Male SD rats were received 0.1 mL injections of FCA(10 g·L^-1)emulsion into the right hind metatarsal foot pad for arthritis induction.After that,rats were randomly divided into six groups,namely control group,untreated group,dexamethasone(DEX,2.5 mg·kg^-1)group,low(5 mg·kg^-1),medium(10 mg·kg^-1)and high(20 mg·kg^-1)doses of ginsenoside Rb1 groups,and treated intraperitoneally at the above dosage once a day for 2 weeks.After treatment,paw swelling and arthritis indexes were evaluated,the thymus and spleen index were calculated as well.HE staining were used to observe the joint histopathology in rats.Rat ELISA kits were used to determinate the TNF-α,IL-1βand IL-6 levels.Western blotting were used to detect the related protein expression of NF-κB signaling pathway in the tissues of inflamed joints.RESULTS Rb1 significantly decreased the paw swelling and arthritis index,Compared with AIA group.HE staining results revealed that medium and high doses of Rb1 significantly reduced synovial inflammatory cell infiltration,synovial lining hyperplasia and bone destruction,compared with AIA group.Elisa results showed that Rb1 significantly decreased the TNF-α,IL-1β and IL-6 levels(P<0.05,P<0.01).Western blotting results revealed that the expression of p-IκB and p-P65 were significantly reduced in 20 mg·kg^-1 of Rb1 group,compared with AIA group(P<0.05,P<0.01).CONCIUSION Rb1 manifests therapeutic anti-inflammatory effects on rats with AIA,poten⁃tially through a mechanism of inhibiting activation of the NF-κB.
基金National Natural Sciences Foundation of China(8187302681473373+4 种基金8173009681603316U1402221)；CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-004)PUMC Graduate Education and Teaching Reform Project(10023201600801)
文摘Panax Ginseng has been used for thousands of years in traditional Chinese medicine(TCM)as a tonic to improver stamina and vitality.Ginsenoside Rg1(Rg1),a saponin extracted from Panax ginseng,is considered one of the most potent pharmacological candidates among TCM.In various diseases related to nervous system,Rg1 has shown excellent pharmacological activities.①Stroke:Rg1 has been well documented to be effective against ischemic/reperfusion(I/R)neuronal injury.A systematic review and meta-analysis revealed a marked efficacy of Rg1 in experi⁃mental acute ischemic stroke,as manifested by its ability to reduce infract volume and improve neurological score.The protective effects of Rg1 were abolished by injecting of AAV-HIF-miR-144-shRNA into the predicted ischemic penumbra.②Depression:In addition,Rg1 showed antidepressive effects in chronic unpredictable mild stress(CUMS)model of depression and in gonadectomized(GDX)model of neuroendocrine disturbance.Rg1 displayed antidepressant activity through the modulation of HPA and HPG axis,markedly alleviated depression-like behavior in rats.Long-term Rg1 treat⁃ment of CUS-exposed rats also significantly prevented the decrease in dye diffusion and improved the ultrastructure of astrocyte gap junctions in the PFC.Rg1 upregulated Cx43 expression in PFC reduced by CUS exposure,indicating beneficial effects on the functional activity of gap junction channels in the brain.③Parkinson disease(PD):Oral treatment with Rg1 significantly attenuated high MPTP-induced mortality,behavior defects,loss of dopamine neurons and abnormal unltrastructure changes in SNpc.It regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as TNF-alpha and IL-1βin SNpc.Rg1 also alleviated the unusual MPTP-induced increase in oligomeric,phosphorylated and disease-relatedα-synuclein in SNpc.④Alzheimer disease(AD):Okadaic acid(OKA)intracerebroventricular injection induced memory impairment,including changes in the ability of orientation navigate,spatial probe and relearning memory in behavioral test of Morris water maze(MWM).OKA treated rats showed memory impair⁃ment including increasing of phospho-tau,decreasing of phospho-GSK3βand the formation ofβ-amyloid in special brain regions,which were reversed by Rg1.The possible neuroprotective mechanism might be that Rg1 decreases OKAinduced memory impairment through GSK3β/tau signaling pathway and/or attenuating Aβformation.Meanwhile,Rg1 activated ERK/MAPK pathway by CaMKIIα,and the activation of CREB was not only dependent on ERK induced by Rg1.Additionally,Rg1 inhibited microglial activation by suppressing Iba1 expression.Rg1 inhibited the inflammation mediated by LPS through suppressing NF-κB and MAPK pathway,which provided the explanation for its therapeutic ef⁃fect on neurodegenerative diseases.
基金National Nature Science Foundation of China(81773989and 81530098)
文摘OBJECTIVE To identify the bioactive anti-angiogenic constitutes targeting tumor endothelial cells(TECs)in Shenmai Injection(SMI).METHEODS For pharmacokinetic(PK)studies,Balb/c mice harboring human colorectal cancer(LoVo)xenografts were treated with SMI 10 mL·kg^-1 daily for 1 or 8 d.Multidimensional PK profiles of ginsenosides in plasma,subcutaneous tumors,and TECs were investigated.For PD studies,the tumor-bearing mice Intravital multi-photon imaging and CD31 immunofluorescence staining were used to evaluate the number of microves⁃sels and braches.Double staining of CD31 and α-SMA was performed to evaluate pericytes coverage ratios around vessels.ELISA was performed to determine the concentrations of VEGF and FGF in tumor tissues.For synergistic anti-tumor study,the tumor-bearing mice were treated with SMI 10 mL·kg^-1 daily,Rd 5 mg·kg^-1 daily with or without 5-FU 15 mg·kg^-1 every 3 d for 20 d.HPLC-MS/MS was used to determine the concentrations of 5-FU in plasma and tumor tissues.RESULTS SMI decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and improved vascular pericytes coverage(P<0.05).PK studies showed that the concentrations of protopanaxadiol-type(PPD)ginsenosides(Rb1,Rb2/Rb3,Rc,and Rd)in both,plasma and tumors,were higher than those of protopanaxatriol-type(Rg1 and Re)and oleanane-type(Ro)ginsenosides.Among PPD ginsenosides,Rd exhibited the greatest concentrations in tumors and TECs after repeated injection.In fact,the proportion of Rd in the detectable components of SMI gradually increased in the following order:SMI formula(2.8%),plasma(16.0%),tumor tissues(34.3%),and TECs(40.3%).In vivo bioactivity results showed that Rd 5 mg·kg^-1 daily significantly decreased the number of microvessels(P<0.05)and vessel branches(P<0.05)and increased pericytes coverage(P<0.05)while Rd 0.5 mg·kg^-1 daily,Rb1 and Rg1 had no significant effect on them.Rd 5 mg·kg^-1 suppressed the expression of VEGF and FGF simultaneously.Rd 5 mg·kg^-1 enhanced the antitumor effect of 5-FU via increasing the distribution of 5-FU in tumor tissues(P<0.05)in xenograft mice.CONCLUSION Ginsenoside Rd may be the major bioactive anti-angiogenic constituent targeting TECs after SMI treatment.
基金The project supported by Lee Foundation Grant(TCH and KHL,R-184-000-200-720)and research scholarship(WHN)
文摘OBJECTIVE Panax ginseng C.A.Meyer(ginseng)is a well-known medicinal plant worldwide and a key ingredient in many commercially-available health products.It is used as a tonic for invigoration and for tification in times of fatigue and debility or declining capacity for work and concentration.Previous in-house study has surveyed over three hundred ginseng and ginseng products(including P.ginseng,P.quinquefolius,P.notoginseng,P.pseudoginseng)available in Singapore.This review presents an overview of the pharmacological activities and herb-drug interactions of P.ginseng and its ginsenosides.METHODS Literature searches of PubMed and ScienceDirect were done to identify pharmacological activities and herb-drug interactions of P.ginseng,its extracts and its chemical components,including ginsenosides.Studies of whole plant extracts include both White ginseng and Red ginseng.The studies for the pharmacological activities of whole plant extract were limited to those published from 2009 to 2015.There was no restriction on the time frame of other studies.Terms such as″P.ginseng″,″Ginsenosides″were searched.Studies found included in vitro assays,in vivo animal studies,human clinical trials as well as individual case reports.RESULTS A total of 112 studies were found on whole plant extracts and 257 studies on its individual components.Whole plant extracts of ginseng were found to possess over fifty different pharmacological activities,while its individual components exhibit parts of this spectrum.P.ginseng was found to interact with drugs such as 5-fluorouracil,irinotecan,mitomycin C,docetaxel,cisplatin,alcohol,midazolam,warfarin,phenelzine,raltegravir and imatinib.CONCLUSION P.ginseng and its components exhibit a wide range of pharmacological activities and interact with some drugs.There remain much opportunities for future research.
