THE CLINICAL EVALUATION OF ANGIOGENESIS INHIBITOR-20(R)-GINSENOSIDE RG_3 IN LUNG CANCER

Objective The aim of the study was to make a further evaluation of Ginsenoside Rg3. Methods The clinical effects of the drug on moderate and advanced lung cancer, including side effects, were observed. Results Ginsenoside Rg3 improved chemotherapy significantly. The clinical relief rate of patients treated with antiangiogenic agent 20 (R) Ginsenoside Rg3 was 36.6%, which was higher than that of the patients not treated with it (16.7%)( P <0.05). It had no significantly different effects on lung cancers of different types of tissues ( P >0.05). It provided better treatment on the cancer at early stage than that at advanced stage ( P <0.05). Moreover the living qualities of the patients were improved notably ( P <0.05). Conclusion Combined with chemotherapy, angiogenesis inhibitor 20(R) Ginsenoside Rg3 can improve clinical therapeutic efficacy and the living qualities of patients significantly.

Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma

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.

Ginsenoside Rg1 protects against ischemia-induced neuron damage by regulating the rno-miRNA-27a-3p/PPARγaxis

A preliminary miRNA screening showed that expression levels of rno-miRNA-27a-3p were significantly increased in the serum and brain tissues of rats undergoing cerebral ischemia.In recent years,there is evidence of the protective capacity of the saponins extracted from panax ginseng and its primary active ingredient ginsenosideRg1oncerebral ischemic injury.Methods:Fetal rat neurons(FRNs)were cultured in glucose-and-serumfree medium and exposed to hypoxia to establish a cerebral ischemia model in vitro(oxygen and glucose deprivation model,OGD).Antioxidant indexes(CAT,SOD),inflammatory markers(MPO,TNF-αand IL-6),and the expression of apoptosis and proliferation associated proteins(NF kB-p65,Caspase 3-cleaved,BCL-2)were examined.Results:Pre-treatment of Rg1(30–100μg/mL)could effectively inhibit the decline of antioxidant indexes(CAT,SOD)and increase in inflammatory markers(MPO,TNF-αand IL-6),and effectively inhibited the apoptosis in FRNs induced by OGD in a gradient-dependent manner.The mechanism analysis showed that the role of Rg1 in protecting against ischemia-induced neuron damage depends on its indirect up-regulation of PPAR protein via suppression of rnomiRNA-27a-3p.Moreover,these effects of Rg1 could be reversed by exogenous rno-miRNA-27a-3p and PPAR gene silencing in FRNs exposed to OGD.Conclusion:To summarize,our study demonstrates that Rg1 could effectively attenuate neuronal damage caused by cerebral ischemia via the rno-miRNA-27a-3p/PPARγpathway.Further,clarification of the novel mechanism will certainly improve our previous understanding of the role of Rg1 and enhancing its level in treatments for alleviating ischemic brain injury.

Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice

Heavy alcohol consumption results in alcoholic liver disease(ALD)with inadequate therapeutic options.Here,we first report the potential beneficial effects of ginsenoside Rk2(Rk2),a rare dehydroprotopanaxadiol saponin isolated from streamed ginseng,against alcoholic liver injury in mice.Chronic-plus-single-binge ethanol feeding caused severe liver injury,as manifested by significantly elevated serum aminotransferase levels,hepatic histological changes,increased lipid accumulation,oxidative stress,and inflammation in the liver.These deleterious effects were alleviated by the treatment with Rk2(5 and 30 mg/kg).Acting as an nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inhibitor,Rk2 ameliorates alcohol-induced liver inflammation by inhibiting NLRP3 inflammasome signaling in the liver.Meanwhile,the treatment with Rk2 alleviated the alcohol-induced intestinal barrier dysfunction via enhancing NLRP6 inflammasome in the intestine.Our findings indicate that Rk2 is a promising agent for the prevention and treatment of ALD and other NLPR3-driven diseases.

Ginsenoside Rb1 improves energy metabolism after spinal cord injury

Mitochondrial damage caused by oxidative stress and energy deficiency induced by focal ischemia and hypoxia are important factors that aggravate diseases.Studies have shown that ginsenoside Rb1 has neurotrophic and neuroprotective effects.However,whether it influences energy metabolism after spinal cord injury remains unclear.In this study,we treated mouse and cell models of spinal cord injury with ginsenoside Rb1.We found that ginsenoside Rb1 remarkably inhibited neuronal oxidative stress,protected mitochondria,promoted neuronal metabolic reprogramming,increased glycolytic activity and ATP production,and promoted the survival of motor neurons in the anterior horn and the recovery of motor function in the hind limb.Because sirtuin 3 regulates glycolysis and oxidative stress,mouse and cell models of spinal cord injury were treated with the sirtuin 3 inhibitor 3-TYP.When Sirt3 expression was suppressed,we found that the therapeutic effects of ginsenoside Rb1 on spinal cord injury were remarkably inhibited.Therefore,ginsenoside Rb1 is considered a potential drug for the treatment of spinal cord injury,and its therapeutic effects are closely related to sirtuin 3.

Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance

Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.

人参皂甙Rg_3对免疫功能的影响

对人参皂甙Ｒｇ３的免疫功能进行了实验研究，结果表明：人参皂甙Ｒｇ３能明显提高小鼠碳粒廓清速率、免疫器官重量、血清溶血素含量、脾淋巴细胞转化和ＮＫ活性，其结果均具有显著性差异（Ｐ＜０．０５），表明人参皂甙Ｒｇ３具有提高免疫功能的作用。

人参皂苷Rg_3对H_2O_2导致海马神经元损伤的保护作用研究

目的探讨人参皂苷Rg3对H2O2所致海马神经元损伤的保护作用及其可能机制。方法人参皂苷Rg3预处理体外培养C57小鼠胎鼠海马神经元,再加入H2O2继续培养,显微镜观察细胞状态并采用细胞活性检测(CCK-8)神经元的活性,生化法测定乳酸脱氢酶(LDH)释放量和丙二醛(MDA)、超氧化物歧化酶(SOD)的活性,实时荧光定量聚合酶链式反应(RT-PCR)检测神经元凋亡相关基因Caspase-3 mRNA的表达。结果与模型组比较,中、高浓度人参皂苷Rg3预处理组细胞状态好于模型组,细胞活性明显增强,培养液中LDH的漏出量明显降低,细胞内MDA的生成明显减少,SOD活性增强,Caspase-3 mRNA表达显著下调(P<0.05)。结论人参皂苷Rg3预处理对H2O2所致海马神经元的损伤具有保护作用。

人参皂苷Rg_(3)对人晶状体上皮细胞氧化应激损伤的影响

目的探讨人参皂苷Rg_(3)对过氧化氢诱导的人晶状体上皮细胞氧化损伤的改善作用及对核转录因子E2相关因子2(nuclear factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)信号通路的调节作用。方法用不同浓度人参皂苷Rg_(3)处理过氧化氢诱导的SRA01/04细胞,用噻唑盐(methyl thiazolyl tetrazolium,MTT)法检测细胞存活率。将第3代对数生长期SRA01/04细胞随机分为正常组、氧化损伤组(用200μmol∙mL^(−1)过氧化氢处理)、人参皂苷Rg_(3)低剂量组和人参皂苷Rg_(3)高剂量组(分别用40、80μg∙mL^(−1)人参皂苷Rg_(3)处理6 h,更换培养基后用200μmol∙mL^(−1)过氧化氢处理12 h),用MTT法检测细胞存活率,用流式细胞仪检测细胞凋亡率,用试剂盒检测丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxidedismutase,SOD)和谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)的含量,用蛋白印迹法检测Nrf2、Kelch样环氧氯丙烷相关蛋白1(Kelch like epichlorohydrin related protein 1,Keap1)和HO-1蛋白的相对表达量。结果与0μg∙mL^(−1)人参皂苷Rg_(3)组比较,10、20、40、80μg∙mL^(−1)人参皂苷Rg_(3)组的细胞存活率逐渐升高(P<0.05)。与正常组比较,氧化损伤组的细胞存活率、SOD和GSHPx含量以及Nrf2、Keap1和HO-1蛋白相对表达量降低,细胞凋亡率和MDA含量升高(P<0.05);与氧化损伤组比较,人参皂苷Rg_(3)低剂量和人参皂苷Rg_(3)高剂量组的细胞存活率、SOD和GSH-Px含量以及Nrf2、Keap1和HO-1蛋白的相对表达量升高,细胞凋亡率和MDA含量降低(P<0.05);人参皂苷Rg_(3)低剂量和人参皂苷Rg_(3)高剂量组各项指标水平变化规律相同,人参皂苷Rg_(3)高剂量组更显著(P<0.05)。结论人参皂苷Rg_(3)可抑制过氧化氢诱导的人晶状体上皮细胞凋亡,减轻氧化应激损伤,其可能是通过激活Nrf2/HO-1信号通路发挥调节作用的。

20(S/R)-人参皂苷Rg_3的制备及调节Th1/Th2免疫失衡活性

采用醋酸溶液作为提取溶剂,使西洋参叶中的二醇组人参皂苷在提取过程中发生降解,从而直接获得20(S)-人参皂苷Rg_3和20(R)-人参皂苷Rg_3,并对其调节Th1/Th2免疫失衡活性进行了研究.正交实验结果表明,当醋酸浓度为50%(体积分数),提取温度为80℃,提取时间为1 h时,20(S)-人参皂苷Rg_3和20(R)-人参皂苷Rg_3的转化率最高,分别为12. 30%和14. 80%.将20(S)-人参皂苷Rg_3和20(R)-人参皂苷Rg_3处理后的朗格汉斯状树突细胞(LDCs)分别作用于小鼠抗原诱导的Th1/Th2免疫失衡模型,发现细胞上层清液中IL-4的水平均显著降低,说明20(S)-人参皂苷Rg_3和20(R)-人参皂苷Rg_3对小鼠Th1/Th2免疫失衡具有调节作用.本文不仅建立了一种制备20(S)-人参皂苷Rg_3和20(R)-人参皂苷Rg_3的新方法,也为人参皂苷Rg_3在免疫系统疾病中的应用提供了新的科学依据.

人参皂苷Rg_3抑制B16黑色素瘤生长和诱导凋亡的实验研究

目的观察人参皂苷Rg3抑制黑色素瘤生长和诱导其凋亡的作用并探讨其可能的作用机制。方法采用B16黑色素瘤实体瘤模型和TUNEL(TdT-mediated dUTP nick-end labeling)染色观察Rg3对黑色素瘤生长和诱导凋亡的作用,免疫荧光染色方法检测caspase-3的表达情况。结果实体瘤模型中,Rg3各组瘤重明显低于对照组(P<0.01),并且TUNEL染色和caspase-3免疫荧光染色见Rg3各组细胞阳性率均高于对照组(P<0.05)。结论Rg3抑制B16黑色素瘤生长,并且促进肿瘤细胞caspase-3的活化和表达,诱导肿瘤细胞凋亡。

HPLC法同时测定腰息痛胶囊中3种活性成分含量

目的 建立HPLC法同时测定腰息痛胶囊中的三七皂苷R_(1)、人参皂苷Rg_(1)、人参皂苷Rb_(1)的含量。方法 采用Omini MP C_(18)(4.6 mm×200 mm,5μm)为色谱柱;流动相为乙腈-0.1%磷酸溶液,梯度洗脱;流速为0.7 ml/min;检测波长为203 nm;柱温为25℃。结果 三七皂苷R_(1)、人参皂苷Rg_(1)、人参皂苷Rb_(1)分别在40.402~1010.500,40.480~1012.000,41.480~1037.000μg范围内呈线性关系(r<0.99);平均加样回收率分别为97.8%,97.5%,98.7%(RSD<2.0%,n=6);精密度、重复性等试验均符合规定。结论 此法简便易行、结果科学,可为中西药复方制剂腰息痛胶囊中的3种皂苷类成分定量控制提供技术依据。

人参皂苷Rg_3对培养人视网膜色素上皮细胞增生的抑制作用

目的 研究人参皂苷Rg3(Ginsenoside Rg3)对体外培养视网膜色素上皮 (RPE)细胞增生的直接抑制作用及可能机制。方法 通过活细胞计数法与MTT比色法分别检测不同浓度 (10、2 0、5 0、80、10 0、15 0mg L)Rg3和Rg380mg L在不同作用时间 (6～ 12 0h)对RPE细胞增生及代谢的影响。结果 Rg3组细胞增殖受到抑制并出现细胞脱落 ,Rg310 0mg L具有最强的抑制效应 ,其明显抑制效应在 6h即出现 ,96h达高峰。Rg3组A值明显低于对照组 ,RPE细胞生存率下降。结论 Rg3可能通过抑制钙内流促进钾外流改变细胞膜电位、干扰RPE细胞代谢 。

基体辅助激光解吸电离飞行时间质谱用于人参皂甙Rg_3的定量分析

考察了基体辅助激光解吸电离时间飞行质谱用于人参皂甙Rg3 定量分析时内标的选择。加入棉子糖作为内标时 ,Rg3 的定量标准曲线的回归系数R2 =0 .938,平均相对误差为 2 8 6 % ;加入性质相近的芦丁后 ,Rg3 的定量标准曲线的回归系数R2 =0 993,平均相对误差为 7 5 %。分辨率的提高以及采用Rg3 和内标物的质谱峰的相对面积来代表Rg3

UPLC-MS/MS测定心悦胶囊中6个皂苷类成分的含量

目的:采用超高效液相色谱-质谱法(UPLC-MS/MS)建立心悦胶囊中主要成分人参皂苷Rg_(1)、人参皂苷Re、人参皂苷Rb_(1)、拟人参皂苷F_(11)、人参皂苷Rd和20(S)-人参皂苷F1的含量测定方法。方法:使用Waters ACQUITY BEH C_(18)色谱柱(100 mm×2.1 mm,1.7μm),以乙腈-水为流动相,梯度洗脱,流速为0.5 mL·min^(–1),柱温为40℃,电喷雾电离源,多反应离子监测扫描方式进行检测。结果:6个成分分别在质量浓度为9.638~963.800、9.839~983.900、9.951~995.100、5.270~1054.000、9.608~960.800、4.905~981.000 ng·mL^(–1)时与峰面积线性关系良好(r>0.998),平均加样回收率(RSD)分别为96.9%(2.2%)、100.1%(1.5%)、97.2%(1.8%)、98.5%(2.3%)、96.6%(2.8%)、100.2%(3.5%)。结论:所建立的方法快速、准确、灵敏度高,可用于心悦胶囊中西洋参茎叶总皂苷的质量控制。

人参皂苷Rb1对过敏性哮喘大鼠炎症反应、免疫功能及JAK2/STAT3信号通路的影响

目的探讨人参皂苷Rb1对过敏性哮喘大鼠炎症反应、免疫功能、Janus激酶(JAK)2/信号转导和转录激活因子(STAT)3信号通路的影响。方法卵清蛋白致敏建立过敏性哮喘大鼠模型,造模成功的SD大鼠随机分成模型组、地塞米松组(0.5 mg/kg)、人参皂苷Rb1低剂量组(25 mg/kg)、人参皂苷Rb1高剂量组(50 mg/kg),每组14只。取14只健康大鼠设为对照组,各组腹腔注射相应药物处理14 d。酶联免疫吸附试验检测大鼠血清白细胞介素(IL)-4、肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、免疫球蛋白(Ig)E水平,苏木素-伊红染色观察肺组织病理变化并进行肺损伤评分,分别采用荧光定量聚合酶链反应(PCR)法和Western印迹法测定大鼠肺组织JAK2、STAT3 mRNA和蛋白表达水平。结果对照组肺组织结构正常,未观察到病理学改变;模型组肺组织出现肺泡壁充血和炎性细胞浸润的明显病理变化;地塞米松组、人参皂苷Rb1高剂量组肺组织损伤的严重程度明显减轻,炎性细胞浸润明显被抑制;人参皂苷Rb1低剂量组肺组织仍可见炎症反应,但较模型组程度轻。与对照组比较,模型组血清IL-4、TNF-α、IgE水平、肺损伤评分、肺组织JAK2、STAT3 mRNA和蛋白表达水平显著升高,IFN-γ水平显著降低(P<0.05);与模型组比较,地塞米松组、人参皂苷Rb1低、高剂量组血清IL-4、TNF-α、IgE水平、肺损伤评分、肺组织JAK2、STAT3 mRNA和蛋白表达水平明显降低,IFN-γ水平明显升高(P<0.05);人参皂苷Rb1高剂量组上述指标水平变化明显优于人参皂苷Rb1低剂量组(P<0.05);地塞米松组和人参皂苷Rb1高剂量组上述指标水平变化差异无统计学意义(P>0.05)。结论人参皂苷Rb1对过敏性哮喘大鼠具有治疗作用,可改善过敏性哮喘大鼠肺损伤,减轻炎症反应,提高免疫功能,其机制可能与抑制JAK2/STAT3信号通路的激活有关。

Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells

AIM:To investigate the effects of ginsenoside Rh2 on the human pancreatic cancer cell line Bxpc-3.METHODS:The human pancreatic cancer cell line Bxpc-3 was cultured in vitro and treated with or without ginsenoside Rh2.Growth rates for Bxpc-3 cells were assessed by methyl thiazolyl tetrazolium(MTT) and colony formation assays.Cell cycle changes were analyzed by flow cytometry.Apoptosis was measured by flow cytometry and Hoechst 33258 fluorescence staining.A scratch assay and a Matrigel invasion assay were used to detect cell migration and invasion.Expression of Bax,Bcl-2,survivin,cyclin D1,matrix metalloproteinase(MMP)-2,MMP-9,cleaved caspase-3,caspase-8,and caspase-9 mRNA were determined by reverse transcriptase-polymerase chain reaction(RT-PCR).Bax,Bcl-2,survivin,cyclin D1,cleaved caspase-3,caspase-8 and caspase-9 protein levels were examined by western blotting.Expression of MMP-2 and MMP-9 proteins in culture supernatants were determined by enzymelinked immunosorbent assay(ELISA).RESULTS:Rh2 significantly inhibited Bxpc-3 cell proliferation in a dose-and time-dependent manner,as evaluated by the MTT(P < 0.05) and colony formation assays(P < 0.05).Compared to the control group,Rh2 significantly increased the percentage of Bxpc-3 cells in the G 0 /G 1 phase from 43.32% ± 2.17% to 71.32% ± 1.16%,which was accompanied by a decrease in S phase(from 50.86% ± 1.29% to 28.48% ± 1.18%) and G 2 /M phase(from 5.81% ± 1.19% to 0.20% ± 0.05%) in a dose-dependent manner(P < 0.05),suggesting that Rh2 arrested cell cycle progression at the G 0 /G 1 phase,as measured by flow cytometry.Compared to the control group,cells treated with Rh2 showed significantly higher apoptosis ratios in a dosedependent manner(percentage of early apoptotic cells:from 5.29% ± 2.28% to 38.90% ± 3.42%(F = 56.20,P < 0.05);percentage of late apoptotic cells:from 4.58% ± 1.42% to 36.32% ± 2.73%(F = 86.70,P < 0.05).Rh2 inhibited Bxpc-3 cell migration and invasion,as detected by scratch wound healing assay and Matrigel invasion assay [percentages of scratch wound healing for 12 h,24 h and 48 h(control vs experimental group):37.3% ± 4.8%vs 18.30% ± 1.65%,58.7% ± 3.5% vs 38.00% ± 4.09% and 93.83% ± 4.65% vs 65.50% ± 4.09%,respectively;t = 6.489,t = 6.656 and t = 7.926,respectively,P < 0.05;the number of cells invading at various concentrations(0 μmol/L,35 μmol/L,45 μmol/L and 55 μmol/L):81.10 ± 9.55,46.40 ± 6.95,24.70 ± 6.88 and 8.70 ± 3.34,respectively(F = 502.713,P < 0.05)].RT-PCR,western blotting or ELISA showed that mRNA and protein expression of Bax,cleaved caspase-3 and caspase-9 were upregulated(P < 0.05),while mRNA and protein expression of Bcl-2,survivin,cyclin D1,MMP-2 and MMP-9 were downregulated(P < 0.05).CONCLUSION:Ginsenoside Rh2 inhibits proliferation,migration and invasion and induces apoptosis of the human pancreatic cancer cell line Bxpc-3.

Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injury

Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/ reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de- pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper- fusion injury. These findings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice

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.

Effect of the structure of ginsenosides on the in vivo fate of their liposomes

To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.