Heat stress(HS)reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases.Ginsenoside Rg3(G-Rg3)is a representative component of ginseng rare saponin and can prote...Heat stress(HS)reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases.Ginsenoside Rg3(G-Rg3)is a representative component of ginseng rare saponin and can protect against multiple organs,also used as functional food to adjust the balance of the human body,but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored.The aim of the present study,G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS.All mice were divided into four groups as follows:normal group,HS group,and HS+G-Rg3(5 and 10 mg/kg)groups.G-Rg3 was administered orally for 14 days,then exposed to a single scrotal heat treatment(43°C,18min)on the 7th day.After HS treatment,the morphology of testis and epididymis changes,and caused a significant loss of multinucleated giant cells,desquamation of germ cells in destructive seminiferous tubules,and degenerative Leydig cells,further destroying the production of sperm.After administration G-Rg3(5 and 10 mg/kg/day)for 2 weeks,the spermatogenic-related indexes of testosterone levels and superoxide dismutase(SOD)activity,glutathione(GSH)content significantly(p<0.01)increase compared with the HS group.Moreover,G-Rg3 treatment effectively ameliorated the production of malondialdehyde(MDA)(p<0.05 or p<0.01).Importantly,G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1(HO-1),hypoxia-inducible factor-1α(HIF-1α),and heat shock protein 70(HSP70)but also modulating the Bcl-2 family(p<0.01 or p<0.001)and activation of mitogen-activated protein kinase(MAPK)signaling pathways(p<0.01).For most of the parameters tested,the HS+G-Rg3(10 mg/kg)group exhibited potent effects compared with those exhibited by the low dose(5 mg/kg)group.In conclusion,the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.展开更多
Objective:To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors.Methods:Eight...Objective:To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors.Methods:Eight-week-old C57BL/6J male mice were fed a high-fat diet for 12 successive weeks to construct the obese model.C57BL/6J male mice were fed a standard chow diet to construct normal control group.After 8 weeks of intervention with ginsenoside rg3,the food intake,body weight,body fat mass,blood sugar,and lipid profiles of the mice in each group were detected.Hematoxylin and eosin(HE)staining was used to observe the histological morphology of the adipose tissues.Real-time polymerase chain reaction(RT-PCR)and Western blotting(WB)were applied to detect the gene and protein expression levels of peroxisome proliferators-activated receptor gama(PPARg),Peroxisome proliferatoractivated receptor-gamma coactivator-1alpha(PGC-1a),PR domain containing 16(PRDM16),and uncoupling protein 1(UCP-1).Results:Compared to normal control group mice,the body weight,food intake,body fat composition,and blood lipid levels of model group mice increased significantly.After 8 weeks of intervention with ginsenoside rg3,body weight,body fat composition,food intake,and blood lipid profiles decreased.HE staining showed that ginsenoside rg3 can improve white adipocyte hypertrophy to a certain extent.RTPCR and WB demonstrated that ginsenoside rg3 can increase the mRNA and protein expression levels of PPARg,PGC-1a,PRDM16,and UCP-1 in the adipose tissues of obese mice.Conclusion:The weight reduction effect of ginsenoside rg3 may be related to the promotion of white fat browning.展开更多
Objective: To study the inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Methods: Female mice were selected as experimental animals, and breast cancer tu...Objective: To study the inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Methods: Female mice were selected as experimental animals, and breast cancer tumor-bearing mouse models were established and then divided into group A, B, C and D that respectively received saline, recombinant human endostatin, ginsenosides Rg3 and recombinant human endostatin combined with Rg3 intervention; 7 d, 14 d and 21 d after intervention, tumor tissue volume was measured; 21 d after intervention, mice were killed, tumor tissue was collected, and m RNA contents of angiogenesis molecules, invasion molecules, autophagy marker molecules and autophagy signaling pathway molecules were detected. Results: At 7 d, 14 d and 21 d after intervention, tumor tissue volume of group B, C and D was lower than that of group A, and tumor tissue volume of group D was lower than that of group B and C; m RNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, m TOR, PI3 K, Akt, JNK and Beclin-1 in tumor tissue of group B, C and D were significantly lower than those of group A, and LC3-II/LC3-I was significantly higher than that of group A; m RNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, m TOR, PI3 K, Akt, JNK and Beclin-1 in tumor tissue of group D were significantly lower than those of group B and C, and LC3-II/LC3-I was higher than that of group B and C. Conclusions: Endostar combined with ginsenoside Rg3 has stronger inhibiting effect on breast cancer tumor growth in tumor-bearing mice than single drug, and it can inhibit angiogenesis and cell invasion, and enhance cell autophagy.展开更多
In this study, the process of a biodegradable polylactide(PLA) microsphere encapsulating ginsenoside Rg3 was first studied by the emulsion solvent evaporation method, for enhancing solubility and stability of ginsenos...In this study, the process of a biodegradable polylactide(PLA) microsphere encapsulating ginsenoside Rg3 was first studied by the emulsion solvent evaporation method, for enhancing solubility and stability of ginsenoside Rg3. Alabum was also first used as a modifier in this method. The mean diameter of the prepared PLA microspheres containing Rg3 was 40 μm. Ginsenoside Rg3 released from the microspheres was studied by HPLC and detected by UV. It was found that the drug release curve fitted the Model Heller-Baker best.展开更多
The ginsenoside Rgfound in Panax species has extensive pharmacological properties,in particular anti-cancer effects.However,its natural yield in Panax plants is limited.Here,we report a multimodular strategy to improv...The ginsenoside Rgfound in Panax species has extensive pharmacological properties,in particular anti-cancer effects.However,its natural yield in Panax plants is limited.Here,we report a multimodular strategy to improve yields of Rgin a Panax ginseng chassis,combining engineering of triterpene metabolism and overexpression of a lignin biosynthesis gene,phenylalanine ammonia lyase(PAL).We first performed semi-rational design and site mutagenesis to improve the enzymatic efficiency of Pq3-O-UGT2,a glycosyltransferase that directly catalyzes the biosynthesis of Rgfrom Rh.Next,we used clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing to knock down the branch pathway of protopanaxatriol-type ginsenoside biosynthesis to enhance the metabolic flux of the protopanaxadiol-type ginsenoside Rg.Overexpression of PAL accelerated the formation of the xylem structure,significantly improving ginsenoside Rgaccumulation(to 6.19-fold higher than in thecontrol).Wecombinedoverexpression of the ginsenoside aglycon synthetic genes squalene epoxidase,Pq3-O-UGT2,and PAL with CRISPR/Cas9-based knockdown of CYP716A53v2 to improve ginsenoside Rgaccumulation.Finally,we produced ginsenoside Rgat a yield of 83.6 mg/L in a shake flask(7.0 mg/g dry weight,21.12-fold higher than with wild-type cultures).The highproduction system established in this study could be a potential platform to produce the ginsenoside Rgcommercially for pharmaceutical use.展开更多
Background:Previous studies showed that New Zealand-grown ginseng contains an abundance of ginsenosides and that rare less polar ginsenosides,such as Rg3,exhibit more pharmacological activities than polar ginsenosides...Background:Previous studies showed that New Zealand-grown ginseng contains an abundance of ginsenosides and that rare less polar ginsenosides,such as Rg3,exhibit more pharmacological activities than polar ginsenosides,which are the major components of ginseng.Methods:The ginsenoside profile of New Zealand-grown Panax ginseng was manipulated by treatment with acetic acid,sodium hydroxide,pH,and high temperature.The abundance of 23 ginsenosides extracted by different treatments was quantified using high-performance liquid chromatography.Results:Treatment with 0.5 mol/L acetic acid can stimulate the degradation of polar ginsenosides to less polar ginsenosides(5.6%Rg3 was accumulated,P<0.0001).Furthermore,when ginseng root was treated at 121℃ for 100 min in a pH 3.0 acetic acid aqueous solution,the majority of the polar ginsenosides were converted into less polar ginsenosides.Specifically,83.46±3.69%(P=0.0360)of the less polar ginsenosides and 41.01±2.39%(P=0.0412)of Rg3 were enriched.In contrast,alkali treatment did not convert the polar ginsenosides into less polar ginsenosides at mild temperature and less conversion was observed compared with acid treatment at high temperature.Conclusion:This is the first attempt to manipulate the ginsenoside profile of New Zealand-grown ginseng.The conditions(high temperature with low pH)may be modified to produce and enrich the less polar ginsenoside fraction(especially Rg3)from the total ginseng extract.展开更多
A murine primary mammary tumor model was established to investigate the treatment with ginsenosides Rg3.The relationship between ginsenosides Rg3 and primary mammary tumor was explored.Mammary tumor was induced by usi...A murine primary mammary tumor model was established to investigate the treatment with ginsenosides Rg3.The relationship between ginsenosides Rg3 and primary mammary tumor was explored.Mammary tumor was induced by using the 7,12-dimethybenz(a)anthracene(DMBA).Ginsenoside Rg3 was employed for treatment.The incidence of mammary tumor in every group was compared,and the expressions of vascular endothelial growth factor(VEGF)and microvessel density(MVD)were detected by immunohistochemical method.The cell cycle and apoptosis percentage were determined by means offlow cytometry.The incidence of tumor in treatment group was significantly lower than that in control group(60.00%vs 33.33%,P<0.05).The average diameter of mammary tumor was(0.86�0.27)cm in control group and(0.39�0.09)cm in treatment group,with the difference being significant between control and treatment groups(P<0.01).The MVD value was(31.9�5.3)in control group and(20.1�4.9)in treatment group,respectively.There was a significant difference between the two groups(P<0.05).The apoptosis percentage in control group was significantly lower than that in treatment group[(2.47�0.69)%vs(5.67�0.99)%,P<0.05].Ginsenoside Rg3 can play an antitumor role in primary mammary tumor model by inhibiting angiogenesis,cell cycle progression,and promoting cell apoptosis.展开更多
目的探讨人参皂苷Rg3调节CD8^(+)T细胞功能从而增加抗肿瘤的作用,并阐明其作用机制。方法MTT法检测Rg3对CD8^(+)T细胞的影响以及对Rg3作用后的CD8^(+)T细胞对黑色素瘤B16F10的杀伤能力,并通过显微镜进行细胞形态学观察;EDU检测B16F10细...目的探讨人参皂苷Rg3调节CD8^(+)T细胞功能从而增加抗肿瘤的作用,并阐明其作用机制。方法MTT法检测Rg3对CD8^(+)T细胞的影响以及对Rg3作用后的CD8^(+)T细胞对黑色素瘤B16F10的杀伤能力,并通过显微镜进行细胞形态学观察;EDU检测B16F10细胞增殖情况;流式细胞术分析对CD8^(+)T细胞功能作用;Western blot检测相关蛋白表达;实时定量PCR检测mRNA变化。结果Rg3可显著增加CD8^(+)T细胞对肿瘤细胞的杀伤能力,并促进功能性记忆T细胞的转化。Rg3增加T细胞释放杀伤因子IL-2及IFN-γ及其mRNA的表达,增加功能性T细胞(central memory T cell,TCM)的比例。进一步数据显示,Rg3促进功能性T细胞分化进而促进T细胞杀伤活性抗肿瘤与激活MAPK/ERK通路正相关。结论人参皂苷Rg3通过激活MAPK/ERK通路促进CD8^(+)T淋巴细胞的杀伤性作用而增加抗肿瘤作用。展开更多
Objective:To study the effect of arsenic trioxide(As_2O_3)combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measu...Objective:To study the effect of arsenic trioxide(As_2O_3)combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measure the inhibition effect of(As_2O_3)combined Rg3 on NC1-H1299 cells,and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro.A total of 40 tumor-bearing nude mice were randomly divided into normal saline group,(As_2O_3),Rg3 and As_2O_3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As_2O_3,ginseng saponin Rg3 and As_2O_3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made;microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining.Results:After 72 h of injection.inhibition rate of tumor cell in normal saline group,As_2O_3 group.Rg3 group and As_2O_3+Rg3 group was(5.66±0.31)%,(65.58±4.75)%,(44.69±3.32)%and(82.67±5.43)%,respectively.Inhibition rate of tumor cell in As_2O_3 group.Rg3 groap and As_2O_3+Rg3 group was significantly higher than that of normal saline group(P<0.01);inhibition rate of tumor cells of As_2O_3+Rg3 group was significantly higher than that of the two groups given As_2O_3 or Rg3 alone(P<0.01).The tumor volume of As_2O_3 group,Rg3 group and As_2O_3+Rg3 group shrank to(65.38±3.25)%,(77.68±3.43)%and(42.65±3.55)%of the original,tumor volume of saline group was 1.21 times of the original size(P<0.01);Median survival of saline group,Rg3 group,As_2O_3 group were significantly shorter than that of As_2O_3+Rg3 group(P<0.01);co-ordinated intervention ability of As_2O_3+Rg3 on NCI-H1299 cell was significantly higher than that of As_2O_3 or Rg3,separately.Conclusions:As_2O_3 combined with Rg3 can significantly inhibit prolifaration of NCI-H1299 cells in lung cancer,prolong survival fo tumor-bearing nude mice,and promote tumor cell apoptosis,and have significant effect on lung cancer treatment.展开更多
Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,...Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.展开更多
基金the grants of the Jilin Science&Technology Development Plan(Nos.20170101011JC,20200301037RQ and 20190103092JH)the Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization(KF202004).
文摘Heat stress(HS)reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases.Ginsenoside Rg3(G-Rg3)is a representative component of ginseng rare saponin and can protect against multiple organs,also used as functional food to adjust the balance of the human body,but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored.The aim of the present study,G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS.All mice were divided into four groups as follows:normal group,HS group,and HS+G-Rg3(5 and 10 mg/kg)groups.G-Rg3 was administered orally for 14 days,then exposed to a single scrotal heat treatment(43°C,18min)on the 7th day.After HS treatment,the morphology of testis and epididymis changes,and caused a significant loss of multinucleated giant cells,desquamation of germ cells in destructive seminiferous tubules,and degenerative Leydig cells,further destroying the production of sperm.After administration G-Rg3(5 and 10 mg/kg/day)for 2 weeks,the spermatogenic-related indexes of testosterone levels and superoxide dismutase(SOD)activity,glutathione(GSH)content significantly(p<0.01)increase compared with the HS group.Moreover,G-Rg3 treatment effectively ameliorated the production of malondialdehyde(MDA)(p<0.05 or p<0.01).Importantly,G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1(HO-1),hypoxia-inducible factor-1α(HIF-1α),and heat shock protein 70(HSP70)but also modulating the Bcl-2 family(p<0.01 or p<0.001)and activation of mitogen-activated protein kinase(MAPK)signaling pathways(p<0.01).For most of the parameters tested,the HS+G-Rg3(10 mg/kg)group exhibited potent effects compared with those exhibited by the low dose(5 mg/kg)group.In conclusion,the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.
基金This study received support from the Key Research Project of Beijing University of Chinese Medicine(2020-JYB-ZDGG-029)the National Natural Science Foundation of China(81274041 and 81503540)+1 种基金the Key Drug Development Programme of the Ministry of Science and Technology(20122X09103201-005)the International Cooperation Projects of the Ministry of Education(2011DFA30920).
文摘Objective:To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors.Methods:Eight-week-old C57BL/6J male mice were fed a high-fat diet for 12 successive weeks to construct the obese model.C57BL/6J male mice were fed a standard chow diet to construct normal control group.After 8 weeks of intervention with ginsenoside rg3,the food intake,body weight,body fat mass,blood sugar,and lipid profiles of the mice in each group were detected.Hematoxylin and eosin(HE)staining was used to observe the histological morphology of the adipose tissues.Real-time polymerase chain reaction(RT-PCR)and Western blotting(WB)were applied to detect the gene and protein expression levels of peroxisome proliferators-activated receptor gama(PPARg),Peroxisome proliferatoractivated receptor-gamma coactivator-1alpha(PGC-1a),PR domain containing 16(PRDM16),and uncoupling protein 1(UCP-1).Results:Compared to normal control group mice,the body weight,food intake,body fat composition,and blood lipid levels of model group mice increased significantly.After 8 weeks of intervention with ginsenoside rg3,body weight,body fat composition,food intake,and blood lipid profiles decreased.HE staining showed that ginsenoside rg3 can improve white adipocyte hypertrophy to a certain extent.RTPCR and WB demonstrated that ginsenoside rg3 can increase the mRNA and protein expression levels of PPARg,PGC-1a,PRDM16,and UCP-1 in the adipose tissues of obese mice.Conclusion:The weight reduction effect of ginsenoside rg3 may be related to the promotion of white fat browning.
基金supported by Linyi City Science and Technology Development Plan in 2014(No.201413010)
文摘Objective: To study the inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Methods: Female mice were selected as experimental animals, and breast cancer tumor-bearing mouse models were established and then divided into group A, B, C and D that respectively received saline, recombinant human endostatin, ginsenosides Rg3 and recombinant human endostatin combined with Rg3 intervention; 7 d, 14 d and 21 d after intervention, tumor tissue volume was measured; 21 d after intervention, mice were killed, tumor tissue was collected, and m RNA contents of angiogenesis molecules, invasion molecules, autophagy marker molecules and autophagy signaling pathway molecules were detected. Results: At 7 d, 14 d and 21 d after intervention, tumor tissue volume of group B, C and D was lower than that of group A, and tumor tissue volume of group D was lower than that of group B and C; m RNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, m TOR, PI3 K, Akt, JNK and Beclin-1 in tumor tissue of group B, C and D were significantly lower than those of group A, and LC3-II/LC3-I was significantly higher than that of group A; m RNA contents of VEGFA, VEGFB, VEGFC, MMP2, MMP9, p62, m TOR, PI3 K, Akt, JNK and Beclin-1 in tumor tissue of group D were significantly lower than those of group B and C, and LC3-II/LC3-I was higher than that of group B and C. Conclusions: Endostar combined with ginsenoside Rg3 has stronger inhibiting effect on breast cancer tumor growth in tumor-bearing mice than single drug, and it can inhibit angiogenesis and cell invasion, and enhance cell autophagy.
文摘In this study, the process of a biodegradable polylactide(PLA) microsphere encapsulating ginsenoside Rg3 was first studied by the emulsion solvent evaporation method, for enhancing solubility and stability of ginsenoside Rg3. Alabum was also first used as a modifier in this method. The mean diameter of the prepared PLA microspheres containing Rg3 was 40 μm. Ginsenoside Rg3 released from the microspheres was studied by HPLC and detected by UV. It was found that the drug release curve fitted the Model Heller-Baker best.
基金financial support from the National Key Research and Development Program(2020YFA0907903)a key project at the central government level:“The ability to establish a sustainable use for valuable Chinese medicine resources”(2060302)+2 种基金the National Science Foundation of China(91954112 and 31900501)the Young Elite Scientists Sponsorship Program of Tianjin(TJSQNTJ-2020-19)the Scientific Research Transformation Foundation of the Wenzhou Safety(Emergency)Institute of Tianjin University。
文摘The ginsenoside Rgfound in Panax species has extensive pharmacological properties,in particular anti-cancer effects.However,its natural yield in Panax plants is limited.Here,we report a multimodular strategy to improve yields of Rgin a Panax ginseng chassis,combining engineering of triterpene metabolism and overexpression of a lignin biosynthesis gene,phenylalanine ammonia lyase(PAL).We first performed semi-rational design and site mutagenesis to improve the enzymatic efficiency of Pq3-O-UGT2,a glycosyltransferase that directly catalyzes the biosynthesis of Rgfrom Rh.Next,we used clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing to knock down the branch pathway of protopanaxatriol-type ginsenoside biosynthesis to enhance the metabolic flux of the protopanaxadiol-type ginsenoside Rg.Overexpression of PAL accelerated the formation of the xylem structure,significantly improving ginsenoside Rgaccumulation(to 6.19-fold higher than in thecontrol).Wecombinedoverexpression of the ginsenoside aglycon synthetic genes squalene epoxidase,Pq3-O-UGT2,and PAL with CRISPR/Cas9-based knockdown of CYP716A53v2 to improve ginsenoside Rgaccumulation.Finally,we produced ginsenoside Rgat a yield of 83.6 mg/L in a shake flask(7.0 mg/g dry weight,21.12-fold higher than with wild-type cultures).The highproduction system established in this study could be a potential platform to produce the ginsenoside Rgcommercially for pharmaceutical use.
文摘Background:Previous studies showed that New Zealand-grown ginseng contains an abundance of ginsenosides and that rare less polar ginsenosides,such as Rg3,exhibit more pharmacological activities than polar ginsenosides,which are the major components of ginseng.Methods:The ginsenoside profile of New Zealand-grown Panax ginseng was manipulated by treatment with acetic acid,sodium hydroxide,pH,and high temperature.The abundance of 23 ginsenosides extracted by different treatments was quantified using high-performance liquid chromatography.Results:Treatment with 0.5 mol/L acetic acid can stimulate the degradation of polar ginsenosides to less polar ginsenosides(5.6%Rg3 was accumulated,P<0.0001).Furthermore,when ginseng root was treated at 121℃ for 100 min in a pH 3.0 acetic acid aqueous solution,the majority of the polar ginsenosides were converted into less polar ginsenosides.Specifically,83.46±3.69%(P=0.0360)of the less polar ginsenosides and 41.01±2.39%(P=0.0412)of Rg3 were enriched.In contrast,alkali treatment did not convert the polar ginsenosides into less polar ginsenosides at mild temperature and less conversion was observed compared with acid treatment at high temperature.Conclusion:This is the first attempt to manipulate the ginsenoside profile of New Zealand-grown ginseng.The conditions(high temperature with low pH)may be modified to produce and enrich the less polar ginsenoside fraction(especially Rg3)from the total ginseng extract.
文摘A murine primary mammary tumor model was established to investigate the treatment with ginsenosides Rg3.The relationship between ginsenosides Rg3 and primary mammary tumor was explored.Mammary tumor was induced by using the 7,12-dimethybenz(a)anthracene(DMBA).Ginsenoside Rg3 was employed for treatment.The incidence of mammary tumor in every group was compared,and the expressions of vascular endothelial growth factor(VEGF)and microvessel density(MVD)were detected by immunohistochemical method.The cell cycle and apoptosis percentage were determined by means offlow cytometry.The incidence of tumor in treatment group was significantly lower than that in control group(60.00%vs 33.33%,P<0.05).The average diameter of mammary tumor was(0.86�0.27)cm in control group and(0.39�0.09)cm in treatment group,with the difference being significant between control and treatment groups(P<0.01).The MVD value was(31.9�5.3)in control group and(20.1�4.9)in treatment group,respectively.There was a significant difference between the two groups(P<0.05).The apoptosis percentage in control group was significantly lower than that in treatment group[(2.47�0.69)%vs(5.67�0.99)%,P<0.05].Ginsenoside Rg3 can play an antitumor role in primary mammary tumor model by inhibiting angiogenesis,cell cycle progression,and promoting cell apoptosis.
文摘目的探讨人参皂苷Rg3调节CD8^(+)T细胞功能从而增加抗肿瘤的作用,并阐明其作用机制。方法MTT法检测Rg3对CD8^(+)T细胞的影响以及对Rg3作用后的CD8^(+)T细胞对黑色素瘤B16F10的杀伤能力,并通过显微镜进行细胞形态学观察;EDU检测B16F10细胞增殖情况;流式细胞术分析对CD8^(+)T细胞功能作用;Western blot检测相关蛋白表达;实时定量PCR检测mRNA变化。结果Rg3可显著增加CD8^(+)T细胞对肿瘤细胞的杀伤能力,并促进功能性记忆T细胞的转化。Rg3增加T细胞释放杀伤因子IL-2及IFN-γ及其mRNA的表达,增加功能性T细胞(central memory T cell,TCM)的比例。进一步数据显示,Rg3促进功能性T细胞分化进而促进T细胞杀伤活性抗肿瘤与激活MAPK/ERK通路正相关。结论人参皂苷Rg3通过激活MAPK/ERK通路促进CD8^(+)T淋巴细胞的杀伤性作用而增加抗肿瘤作用。
基金supported by New Medical Technology Import Project in Henan Province,Number:2011020113
文摘Objective:To study the effect of arsenic trioxide(As_2O_3)combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measure the inhibition effect of(As_2O_3)combined Rg3 on NC1-H1299 cells,and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro.A total of 40 tumor-bearing nude mice were randomly divided into normal saline group,(As_2O_3),Rg3 and As_2O_3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As_2O_3,ginseng saponin Rg3 and As_2O_3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made;microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining.Results:After 72 h of injection.inhibition rate of tumor cell in normal saline group,As_2O_3 group.Rg3 group and As_2O_3+Rg3 group was(5.66±0.31)%,(65.58±4.75)%,(44.69±3.32)%and(82.67±5.43)%,respectively.Inhibition rate of tumor cell in As_2O_3 group.Rg3 groap and As_2O_3+Rg3 group was significantly higher than that of normal saline group(P<0.01);inhibition rate of tumor cells of As_2O_3+Rg3 group was significantly higher than that of the two groups given As_2O_3 or Rg3 alone(P<0.01).The tumor volume of As_2O_3 group,Rg3 group and As_2O_3+Rg3 group shrank to(65.38±3.25)%,(77.68±3.43)%and(42.65±3.55)%of the original,tumor volume of saline group was 1.21 times of the original size(P<0.01);Median survival of saline group,Rg3 group,As_2O_3 group were significantly shorter than that of As_2O_3+Rg3 group(P<0.01);co-ordinated intervention ability of As_2O_3+Rg3 on NCI-H1299 cell was significantly higher than that of As_2O_3 or Rg3,separately.Conclusions:As_2O_3 combined with Rg3 can significantly inhibit prolifaration of NCI-H1299 cells in lung cancer,prolong survival fo tumor-bearing nude mice,and promote tumor cell apoptosis,and have significant effect on lung cancer treatment.
基金supported by the National Key R&D Program of China(Grant No.:2021YFC2101500)the National Natural Science Foundation of China(Grant Nos.:22078264,21978235,22108224,and 21978236)+2 种基金the Natural Science Basic Research Program of Shaanxi,China(Grant Nos.:2023-JC-JQ-17 and 2023-JCQN-0109)the Xi'an Science and Technology Project,China(Project No.:20191422315KYPT014JC016)Key Research and Development Program of Shaanxi,China(Grant No.:2022ZDLSF05-12).
文摘Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.
