Effect of ginsenoside Rg1 on hematopoietic stem cells in treating aplastic anemia in mice via MAPK pathway

BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

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.

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway

AIM:To construct an in vitro model of oxygen-glucose deprivation/reperfusion(OGD/R)induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion(I/R)injury in 661W cells and the protective effect of ginsenoside Rg1.METHODS:The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro.Apoptosis,intracellular reactive oxygen species(ROS)levels and superoxide dismutase(SOD)levels were measured at different time points during the reperfusion injury process.The injury model was pretreated with graded concentrations of ginsenoside Rg1.Real-time polymerase chain reaction(PCR)was used to measure the expression levels of cytochrome C(cyt C)/B-cell lymphoma-2(Bcl2)/Bcl2 associated protein X(Bax),heme oxygenase-1(HO-1),caspase9,nuclear factor erythroid 2-related factor 2(nrf2),kelch-like ECH-associated protein 1(keap1)and other genes.Western blot was used to detect the expression of nrf2,phosphorylated nrf2(pnrf2)and keap1 protein levels.RESULTS:Compared to the untreated group,the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased(P<0.01).Additionally,the ROS content increased and SOD levels decreased significantly(P<0.01).In contrast,treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na_(2)S_(2)O_(4)treated group(P<0.01).Moreover,Rg1 reduced the levels of caspase3,caspase9,and cyt C,while increasing the Bcl2/Bax level.These differences were all statistically significant(P<0.05).Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment,however,Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na_(2)S_(2)O_(4)treated group(P<0.001).CONCLUSION:The OGD/R process is induced in 661W cells using Na_(2)S_(2)O_(4).Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway.These results suggest a potential protective effect of Rg1 against retinal I/R injury.

Microbiological Transformation of Ginsenoside Rg_1

Forty-nine microbial strains were used to screen their ability for the microbiological transforma-tion of ginsenoside Rg1. Aspergillus niger (3.1858) and Absidia coerulea (3.3538) were found to convert ginsenoside Rg1 efficiently to less polar metabolites. Preparative scale transformation with both fungi Absidia coerulea (3.3538) and Aspergillus niger (3.1858) have resulted in the production of one same metabolite (MT1). Its structure was char-acterized as 6-O-b-D-glucopyranosyl-20(S)-protopanaxatriol (Ginsenoside Rh1) on the basis of its TOF-MS and 1H, 13C NMR spectral data. The biotransformation kinetic curves for Ginsenoside Rg1 and MT1 were reported for the first time, and the biotransformation pathway was proposed.

Ginsenoside Rg1 protects against ischemia reperfusion-induced neurotoxicity through miR-144/Nrf2/ARE pathway

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.

Antidepressant-like Effects of Ginsenoside Rg1 in the Chronic Restraint Stress-induced Rat Model

Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference:control group,model group,and Rg1-treated groups(5 and 10 mg/kg).Except for control group,the groups were exposed to CRS(6 h/day)for 28 days.All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days.The behavioral tests were carried out via the open field test(OFT),sucrose preference test(SPT),forced swim test(FST),and the Morris water maze(MWM)4 weeks following CRS induction.The levels of serum corticosterone(CORT)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the prefrontal cortex(PFC)were analyzed using commercial ELISA kits.The levels of the neurotransmitter(5-HT,5-HIAA,Ach,NE,GABA and Glu)in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry.The protein expression of BDNF,Trkb,Bax and Bcl-2 in the PFC was detected by western blotting.Results Owing to increased sucrose consumption in the SPT,decreased immobility time in the FST,and the improved cognitive performance in MWM,chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depressionlike behaviors(anhedonia,behavioral despair and poor spatial memory)in rats.Moreover,CRS exposure caused evident alterations in the levels of the neurotransmitters(5-HT,5-HIAA,Ach,GABA and Glu)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the PFC and the levels of corticosterone in serum.However,Ginsenoside Rg1 treatment could restore these levels to normal values.Additionally,Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF,Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.Conclusions Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors,in part,by regulating neurotransmitter levels and HPA function,antagonizing oxidative stress and apoptosis,and restoring BDNF-TrkB signaling in PFC.Altogether,our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.

Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model

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.

Pharmacological effects of ginsenoside Rg1 in neuropsychopharmacology

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.

Separation and Purification of Ginsenoside Rg1 from Triol Saponins

[Objectives] This study aimed to optimize the medium-pressure preparation process of high-purity ginsenoside Rg1 from triol saponins. [Methods] The reversed-phase C18 chromatographic separation method was used,and the purity and yield of ginsenoside Rg1 were examined as indicators. [Results]The diameter-height ratio of the C18 column was 1∶ 3. 25. Triol saponins of 0. 2 times the volume of the column were loaded with 20% ethanol. At the elution flow rate of 8 BV/h,1,3 and 0. 5 times the volume of the column was eluted with 30%,30%-40% and 40% ethanol,respectively. Crude ginsenoside Rg1 was concentrated,dissolved in 4-time-voume 95% ethanol,added with 0. 5%activated carbon,refluxed for 40 min,and dried to obtain good-quality ginsenoside Rg1. [Conclusions] After purification,ginsenoside Rg1 with purity higher than 99. 5% can be isolated from triol saponins. The medium-pressure preparation process of ginsenoside Rg1 with purity higher than 99. 5% is provided for the first time. It has been proved by many experiments that the process is stable,feasible and reproducible,and can be used for industrial scale-up production.

STUDY ON THE THERAPEUTIC EFFECTS OF GINSENOSIDE Rg-1 AND GASTRODINE ON AD MODEL RATS INDUCED BY β-AMYLOID PEPTIDE (25-35)

Objective To study the therapeutic effects of Ginsenoside Rg-1 and Gastrodine on rats model of Alzheimer's disease(AD). Methods Aggregated β-Amyloid peptide (25-35) was injected into the lateral ventricle of rats to establish AD models. Ginsenoside Rg-1, Gastrodine and Ginsenoside Rg-1+Gastrodine were intraperitoneally injected into rats of each test group(Ginsenoside Rg-1∶10mg/kg·day; Gastrodine 100mg/kg·day) for 4 weeks, the rats of control group received equal volume of saline. Passive avoidance task and Morris maze test were done to assess the ability of learning and memory. The content of superoxide dismutase (SOD), malondiadehyde (MDA), total-antioxidative capability (T-AOC), Choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissue were measured. Results Ginsenoside Rg-1 and Gastrodine significantly improved learning and memory deficits in the rats with AD induced by β-Amyloid peptide (25-35) (P<0.05). Ginsenoside Rg-1+Gastrodine group were better than Ginsenoside Rg-1 group and Gastrodine group (P<0.05). Ginsenoside Rg-1 reduced the increase of SOD, MDA, but inhibited the decrease of T-AOC, AchE and ChAT; Gastrodine reduced the increase of SOD, MDA, while inhibited the decrease of T-AOC. Gastrodine could also prevent the activity of ChAT and AchE decline in AD rats. Conclusion Both Ginsenoside Rg-1 and Gastrodine have therapeutic effects on rats with AD; Ginsenoside Rg-1 and Gastrodine injection at the same time were better than only using one of them. Their mechanisms might different. Ginsenoside Rg-1 can not only inhibit peroxidation but also increase the activity of AchE and ChAT in brain tissue, while Gastrodine can inhibit peroxidation only, but it can't prevent the decline of ChAT and AchE activity in AD rats.

Ginsenoside Rg1 and Resveratrol Alleviate Acute Kidney Injury Induced by Cisplatin via Downregulation of Autophagy in Mice

Background: Cisplatin, a chemotherapeutic agent, is widely used in the treatment of malignant tumors. Nephrotoxicity, especially acute kidney injury (AKI), is the most common and severe adverse reaction of cisplatin. Resveratrol and ginsenoside Rg1, two natural products, have been found to have renal protective effects. However, the effects and the mechanisms in cisplatin-induced AKI need further investigation. Methods: The mouse models of cisplatin-induced AKI and several treatment groups were established. Male C57BL/6 mice were divided into five groups: saline control group, cisplatin injury group, resveratrol treatment group, Rg1 treatment group, resveratrol and Rg1 combined treatment group. Serological analysis of serum urea nitrogen was aimed to reflect the function of kidney, and histological analysis of renal tissue sections was aimed to assess the damage of proximal convoluted tubules. The expression levels of autophagy-related proteins Beclin 1 and LC3 were detected by western blotting and qRT-PCR respectively. Results: The renal function was improved and renal damage was alleviated in Rg1 and resveratrol alone or combined treatment groups compared with the cisplatin injury group. For the mechanism, treatment with Rg1 and resveratrol alone or in combination decreased the expressions of Beclin 1 both at protein and mRNA levels, decreased LC3II/I protein levels, indicating that autophagy was inhibited by treatment with Rg1 and resveratrol alone or in combination. Conclusion: Resveratrol and Rg1 alleviated the kidney damage caused by cisplatin, and reduced autophagy was involved in the renoprotective effects of resveratrol and Rg1 against cisplatin-induced AKI. This study may provide new evidence to alleviate cisplatin-induced AKI.

Effect of ginsenoside Rg1 on the pro-apoptosis/anti-apoptosis balance in lesions of model rats with spinal cord compression injury

Objective:To study the effect of ginsenoside Rg1 on the pro-apoptosis/anti-apoptosis balance in lesions of model rats with spinal cord compression injury.Methods: Wistar rats were selected as the experimental animals and randomly divided into sham operation group, compression injury group and ginsenoside group, and spinal cord compression injury models were made and then given intraperitoneal injection of 10 mg/kg ginsenoside Rg1 for intervention. 14 d after intervention, the spinal cord tissue was collected from the injured area to determine the mRNA expression of pro-apoptosis genes, anti-apoptosis genes and apoptosis-related signaling pathway genes.Results: Bcl-2, Bcl-xl, NAIP, Survivin, ERK1/2, p38MAPK, JNK, STAT3 and STAT5 mRNA expression in spinal cord tissue of compression injury group were significantly lower than those of sham operation group while Bax, caspase-3, caspase-9 and caspase-12 mRNA expression were significantly higher than those of sham operation group;Bcl-2, Bcl-xl, NAIP, Survivin, ERK1/2, p38MAPK, JNK, STAT3 and STAT5 mRNA expression in spinal cord tissue of ginsenoside group were significantly higher than those of compression injury group while Bax, caspase-3, caspase-9 and caspase-12 mRNA expression were significantly lower than those of compression injury group.Conclusion:Ginsenoside Rg1 can regulate the pro-apoptosis/anti-apoptosis balance in lesions of model rats with spinal cord compression injury.

Effect of ginsenoside Rgl and Rhl on the anti-tumor activity of dendritic cell

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.

人参皂苷Rg_1和Rh_1抗肿瘤作用的研究

目的 :研究人参皂苷 Rh1及其前体 Rg1的整体及离体抗肿瘤作用。方法 :整体实验 4种小鼠移植性肿瘤 :小鼠宫颈癌 - 1 4( U14 )、艾氏腹水癌 ( EAC)、肉瘤 - 1 80 ( S180 )和肝癌腹水型 ( Hep A)腋部皮下接种 ,于接种 1 0 d内 ,每天给药 1次 ,计算各给药组肿瘤抑制率。离体抗肿瘤实验用 3种瘤株 :A375 - S2、T98G 和 He La。结果 :人参皂苷 Rg1( 2 0 0 mg·kg-1,灌胃 )和 Rh1( 4 0和2 0 mg· kg-1,腹腔注射 )对 U14 均具有明显的抑制作用 ( P<0 .0 1 ) ;人参皂苷 Rh1在较高剂量( 4 0 mg·kg-1)时 ,对 EAC也有明显抑制作用 ( P<0 .0 1 )。但人参皂苷 Rg1和 Rh1对 S180 和 Hep A无抗肿瘤作用。离体实验证明 ,Rg1对 He La细胞的增殖有明显的抑制作用 ,Rh1高剂量组( 1 0 0 mg· L-1)对 3种肿瘤细胞均有明显抑制作用。结论 :人参皂苷 Rh1较其前体

人参皂苷Rg_1及其肠内菌代谢产物Rh_1对小鼠免疫细胞功能的影响

目的 初探人参皂苷Rg1 及其肠内菌代谢产物Rh1 对正常小鼠免疫功能的影响。方法 用Rh1 与Rg1 分别处理脾T细胞 ,B细胞及腹腔巨噬细胞 (Mφ) ;MTT比色法测T和B细胞增殖能力 ;中性红比色法测Mφ的吞噬功能 ;Griess法测Mφ释放NO的水平。 结果 Rh1 能促进脾细胞增殖、下调ConA诱导的T细胞增殖 ;Rh1 与Rg1 对LPS诱导的B细胞增殖均无明显作用 ;Rg1 和Rh1 能提高Mφ的吞噬能力和促进NO的释放。 结论 Rg1 及其代谢产物Rh1 可共同作用于T细胞和Mφ而产生免疫调节作用。

西洋参冠瘿组织培养及其人参皂苷Re和人参皂苷Rg_1的产生

考察了培养基组成、培养时间、接种量、pH值、肌醇浓度等对冠瘿组织生长及其人参皂苷含量的影响 ;用HPLC检测了冠瘿组织中人参皂苷Re和人参皂苷Rg1 的含量。高压纸层析电泳证实 ,根癌农杆菌Ti质粒上的T DNA片段已整合进入植物细胞核基因组中。在考察的 6种培养基中 ,White培养基最适合人参皂苷Rg1 的累积(0 0 95 % ) ,MS培养基最适合人参皂苷Re的累积 (0 194 % )。以MS为基本培养基培养 36d、32d时人参皂苷Re和人参皂苷Rg1 累积含量最高 (分别为 0 14 7%和 0 0 6 1% ) ;接种量为 4g、2g (FW flask) ,有利于人参皂苷Re和人参皂苷Rg1的累积 ;培养基pH 5 8时人参皂苷Re含量最高 (0 184 % ) ,培养基pH 5 6时人参皂苷Rg1 累积量最高 (0 0 5 4 % ) ;肌醇浓度为 0 0 5g L时 ,能促进人参皂苷Re合成 (0 182 % ) ,浓度为 0 30g L时 ,有利于人参皂苷Rg1 累积 (0 0 5 5 % )。

肠内菌群对人参皂苷Rg_1的代谢转化作用的研究

目的 :通过离体和整体实验研究大鼠及人的肠道内细菌对人参皂苷Rg1的代谢作用。方法 :用薄层层析及电喷雾质谱检测Rg1的代谢产物。结果 :Rg1在大鼠体内被代谢成一对同分异构体 (Rh1及F1)及苷元 [2 0(S)Protopanaxatriol,Ppt]。但在人的肠道内 ,则代谢物为Rh1及苷元。结论 :Rg1在人和大鼠肠内菌作用下均被代谢 ,但沿不同的代谢途径进行代谢。在大鼠体内 ,代谢模式为 :Rg1Rh1(F1)Ppt ;在人体内 ,代谢模式为Rg1Rh1Ppt。

高效液相色谱法同时测定三七总皂苷中人参皂苷Rg_1、Re、Rb_1与三七皂苷R_1含量

目的建立高效液相色谱法同时测定三七总皂苷中人参皂苷Rg1、Re、Rb1与三七皂苷R1的方法。方法采用高效液相色谱法 ,固定相为氨基键合相 ,流动相为乙腈 水 ( 81∶1 9,V∶V) ,检测波长2 0 3nm。结果三七总皂苷中人参皂苷Rg1、Re、Rb1和三七皂苷R1与其他成分分离良好 ,保留时间分别约为 5 7min、8 9min、2 5 1min和 9 9min。人参皂苷Rg1在 80～ 2 80mg/L(r =0 9992 )、Re在 2 0～ 1 80mg/L(r=0 9993 )、Rb1在 95～ 2 85mg/L(r=0 9991 )、三七皂苷R1在1 8～ 1 4 6mg/L(r=0 9991 )内线性关系良好 ,人参皂苷Rg1、Re、Rb1和三七皂苷R1的回收率分别为 99 1 %、98 4 %、98 6%和 97 1 % ,RSD分别为 2 1 %、2 0 %、2 2 %、2 8%。

人参皂苷-Rg_1对中性粒细胞与血小板之间粘附的影响

目的 探讨人参皂苷 - Rg1 对大鼠血小板与中性粒细胞之间粘附及颈动脉血栓形成的影响。方法 采用Charlton等方法评价人参皂苷 - Rg1 对电刺激大鼠颈动脉血栓形成的作用 ;应用玫瑰花结试验观察对大鼠血小板与中性粒细胞之间粘附的影响。结果 2 5 m g/ kg人参皂苷 - Rg1 使血栓形成时间从对照组的 ( 18.7± 1.8) m in延长到( 3 6.4± 2 .1) min ( P<0 .0 5 ) ;显著降低凝血酶激活的血小板与中性粒细胞间的粘附率 ,其 IC50 为 81.2μm ol/ L。结论 人参皂苷 - Rg1 具有较强的抗血栓的作用 。

参麦注射液中人参皂苷Rg_1和Re药代动力学研究

目的 研究参麦注射液中人参皂苷Rg1和Re人体药代动力学。方法 采用已建立的LC/MS/MS法同时测定人血浆中人参皂苷Rg1和Re浓度,并计算其药代动力学参数。结果 人参皂苷Rg1和Re线性范围为 1 023 -1 023μg·L-1和 1 05-1 050μg·L-1,方法回收率在 99% -105%和 99% -104%,日内、日间RSD值均小于 15%。参麦注射液 60mL经静脉滴注后人参皂苷Rg1和Re的药时曲线均符合二房室开放模型,T1 /2α分别为 0 28h和 0 10h,T1 /2β分别为 2 1h和 1 2h。结论 该法简便、灵敏、特异,适用于血浆中人参皂苷Rg1和Re浓度的测定。参麦注射液中人参皂苷Rg1和Re在人体内血药浓度较低,分布和消除速度较快,药代动力学行为符合二房室模型。