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 T...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.展开更多
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...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.展开更多
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...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.展开更多
<strong>Background:</strong> 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 ad...<strong>Background:</strong> 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. <strong>Methods:</strong> 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. <strong>Results:</strong> 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. <strong>Conclusion:</strong> 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.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 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
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 di...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.展开更多
Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component de...Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.展开更多
[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...[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.展开更多
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 ...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.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
Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from ...Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from neonatal mouse brain were used.Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R).Cell morphology,viability,lactate dehydrogenase(LDH)leakage,apoptosis,glutamate uptake,and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality.Western blot was used to investigate the cyclic adenosine monophosphate(cAMP)and protein kinase B(Akt)signaling pathways.GPCR-G_(s)-specific inhibitors and molecular docking were used to identify target receptors.Results:Rb1 at concentrations ranging from 0.8 to 5μM did not significantly affect the viability,glutamate uptake,or BDNF secretion in normal astrocytes.OGD/R reduced astrocyte viability,increasing their LDH leakage and apoptosis rate.It also decreased glutamate uptake and BDNF secretion by these cells.Rb1 had protective effects of astrocytes challenged by OGD/R,by improving viability,reducing apoptosis,and enhancing glutamate uptake and BDNF secretion.Additionally,Rb1 activated the cAMP and Akt pathways in these cells.When the GPCR-G_(s) inhibitor NF449 was introduced,the protective effects of Rb1 completely disappeared,and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion:Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_(s) mediation.展开更多
We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. Ginsenoside Rg1 was injected intraperitoneal y for 12 we...We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. Ginsenoside Rg1 was injected intraperitoneal y for 12 weeks. Myocardial injury indices and oxidative stress markers were determined. Changes in cardiac ultrastructure were evaluated with transmission electron microscopy. Myocardial apoptosis was assessed via terminal deoxynucleotidyl transferase （TDT）-mediated DNA nick-end labeling （TUNEL） and immunohistochemistry. Ginsenoside Rg1 was as-sociated with a significant dose-dependent reduction in serum levels of creatinine kinase MB and cardiac troponin I, and lessened ultrastructural disorders in diabetic myocardium, relative to the untreated diabetic model rats. Also, compared with the untreated diabetic rats, significant reductions in serum and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1-treated groups, and increased levels of the antioxidants （superoxide dismutase, catalase, and glutathione peroxidase） were detected. TUNEL staining indicated reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be associated with reduced levels of caspase-3 （CASP3） and increased levels of B-cell lymphoma-extra-large （Bcl-xL） in the diabetic myocardium. Ginsenoside Rg1 treatment of diabetic rats was associated with reduced oxidative stress and attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of potential preventative and therapeutic value for cardiovascular injury in diabetic patients.展开更多
Ginsenoside Rg1(GR),a major bioactive compound of traditional Chinese medicine,such as Panax ginseng or Radix Notoginseng,has been shown to exert neuroprotective effects against ischemic stroke.However,pharmacokinetic...Ginsenoside Rg1(GR),a major bioactive compound of traditional Chinese medicine,such as Panax ginseng or Radix Notoginseng,has been shown to exert neuroprotective effects against ischemic stroke.However,pharmacokinetic studies have suggested that GR could not be efficiently transported through the blood–brain barrier.The mechanism by which GR attenuates cerebral ischemic injury in vivo remains largely unknown.Therefore,this study explored potential neuro-protective effects of GR through its systemic metabolic regulating mechanism by using mass spectrometry–based metabolomic profiling.Rats with middle cerebral artery occlusion(MCAO) were treated with GR intravenously.Their metabolic profiles in serum were measured by gas chromatography coupled with mass spectrometry on 1 and 3 days after MCAO.GR exhibited a potent neuro-protective effect by significantly decreasing the neurological scores and infarct volume in the MCAO rats.Moreover,18 differential metabolites were tentatively identified,all of which appeared to correlate well with these disease indices.Our findings suggested that GR carries a therapeutic potential in stroke possibly through a feed-back mechanism by regulating systematic metabolic mediation.展开更多
Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high perf...Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry(LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile,urine, and feces after oral administration(25 mg/kg). Calibration curves offered satisfactory linearity(r40.995)within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1(Rh1), and protopanaxatriol(Ppt) in bile,urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile.Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.展开更多
During the traumatic brain injury(TBI),improved expression of circulatory miR-21 serves as a diagnostic feature.Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and bloodebrain barri...During the traumatic brain injury(TBI),improved expression of circulatory miR-21 serves as a diagnostic feature.Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and bloodebrain barrier(BBB)permeability,reduce nerve apoptosis,restore neural function and ameliorate TBI.We evaluated the role of macrophage derived exosomes-miR-21(M-Exos-miR-21)in disrupting BBB,deteriorating TBI,and Rg1 interventions.IL-1β-induced macrophages(ⅡA)-Exos-miR-21 can activate NF-kB signaling pathway and induce the expressions of MMP-1,-3 and-9 and downregulate the levels of tight junction proteins(TJPs)deteriorating the BBB.Rg1 reduced miR-21-5 p content in ⅡA-Exos(RⅡA-Exos).The interaction of NMIIAe HSP90 controlled the release of Exos-miR-21,this interaction was restricted by Rg1.Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain,enhancing TIMP3 protein expression,MMPs proteolysis,and restricting TJPs degradation thus protected the BBB integrity.Conclusively,Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.展开更多
Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hyp...Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hypoxia,cerebral ischemia and alzheimer’s disease,etc.In the treatment of cerebrovascular diseases,borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs,especially to the brain.The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA(TS IIA),salvianolic acid B(SAB)and ginsenoside Rg1 in FDP.Male healthy Sprague-Dawley(SD)rats were given Danshen extracts,Sanqi extracts(Panax notoginseng saponins)or simultaneously administered Danshen extracts,Sanqi extracts and borneol.Plasma and brain samples were collected at different points in time.The concentration of TS IIA,SAB and Rg1 was determined by UPLC-MS/MS method.The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software.In comparison with Danshen and Sanqi alone,there were significant differences in pharmacokinetic parameters of TS IIA,SAB and Rg1,and the brain distribution of SAB and TS IIA when Danshen,Sanqi and borneol were administrated together.Borneol statistically significant shortened tmax of TS IIA,SAB and Rg1 in plasma and brain,increased the bioavaiability of Rg1,inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain.These results indicated that borneol could affect the multiple targets components and produce synergistic effects.Through accelerating the intestinal absorption and brain distribution,borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.展开更多
Many technologies have been developed for breast reconstruction after lumpectomy.Although the technologies achieved promising success in clinical,there are still many shortages hanging over and trouble the researchers...Many technologies have been developed for breast reconstruction after lumpectomy.Although the technologies achieved promising success in clinical,there are still many shortages hanging over and trouble the researchers.Tissue engineering technology was introduced to plastic surgery that gave a light to lumpectomy patients in breast reconstruction.The unexpected absorption rate,resulting from limited vascularization and low cell survival rate,is a major factor that leads to unsatisfactory results for the previous studies in our lab.In the study,the laminin-modified alginate synthesized by a new method of low concertation of sodium periodate would be mixed with ADSCs and Rg1 in the medium;and then sprayed into a calcium chloride(CaCl2)solution to prepare into microsphere(abbreviated as ADSC-G-LAMS)by bio-electrospray with a power syringe for the mass production and smaller bead size.The developed ADSC-G-LAMS microspheres had the diameter of 232±42μm.Sustained-release of the Rg1 retained its biological activity.WST-1,live/dead staining,and chromosome aberration assay were evaluated to confirm the safety of the microspheres.In in vivo study,ADSC-G-LAMS microspheres combined with autologous adipocytes were transplanted into the dorsum of rats by subcutaneous injection.The efficacy was investigated by H&E and immunofluorescence staining.The results showed that the bioactive ADSC-G-LAMS microspheres could integrate well into the host adipose tissue with an adequate rate of angiogenesis by constantly releasing Rg1 to enhance the ADSC or adipocyte survival rate to join tissue growth and repair with adipogenesis for breast reconstruction after lumpectomy.展开更多
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.81973317,81374007,81870977the Natural Science Foundation of Heilongjiang Province,HL2019H062+1 种基金the Projects of Basic Scientific Research Business Expenses in Higher Education Institutions of Heilongjiang Province,No.2018-KYYWF-MY-005the Students Innovative and the Entrepreneurship Training Scientific Research Foundation of Heilongjiang Province,No.102292017001.
文摘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.
基金Supported by Natural Science Foundation of Guangdong Province(No.2021A1515010513)。
文摘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.
文摘<strong>Background:</strong> 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. <strong>Methods:</strong> 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. <strong>Results:</strong> 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. <strong>Conclusion:</strong> 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.
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.
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.
基金funding support from the Open Funding Project of National Key Laboratory of Human Factors Engineering (No. SYFD150051808K)the National Key Research and Development Program of China (No. 2016YFE0131800)the Highend Talents Recruitments Program (Liu Xin-Min group) of Luzhou Municipal People’s Government and Development of Animal Model on Human Diseases (No. 2016-I2M-2-006)
文摘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.
基金funded by the Science and Technology Innovation Project of the China Academy of Chinese Medical Sciences(Nos.CI2021A04618 and CI2021A01401).
文摘Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.
基金Supported by National Chinese Medicine Standardization Project(ZYBZH-CYN-58)Major Science and Technology Projects in Yunnan Province(2017ZF001)
文摘[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.
文摘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.
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supported by the grant International Cooperation Project of Prevention and Treatment of Major Diseases with Chinese Medicine(GZYYGJ2021047)the High-end Experts Support Program from the Ministry of Science and Technology(DL 2021110001L)the Basic Research Funds from the Ministry of Education(1000061223731).
文摘Objectives:To investigate whether the protective actions of ginsenoside Rb1(Rb1)on astrocytes are mediated through the G_(s)-type G-protein-coupled receptor(GPCR-G_(s)).Methods:Primary astrocyte cultures derived from neonatal mouse brain were used.Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R).Cell morphology,viability,lactate dehydrogenase(LDH)leakage,apoptosis,glutamate uptake,and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality.Western blot was used to investigate the cyclic adenosine monophosphate(cAMP)and protein kinase B(Akt)signaling pathways.GPCR-G_(s)-specific inhibitors and molecular docking were used to identify target receptors.Results:Rb1 at concentrations ranging from 0.8 to 5μM did not significantly affect the viability,glutamate uptake,or BDNF secretion in normal astrocytes.OGD/R reduced astrocyte viability,increasing their LDH leakage and apoptosis rate.It also decreased glutamate uptake and BDNF secretion by these cells.Rb1 had protective effects of astrocytes challenged by OGD/R,by improving viability,reducing apoptosis,and enhancing glutamate uptake and BDNF secretion.Additionally,Rb1 activated the cAMP and Akt pathways in these cells.When the GPCR-G_(s) inhibitor NF449 was introduced,the protective effects of Rb1 completely disappeared,and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion:Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_(s) mediation.
文摘We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. Ginsenoside Rg1 was injected intraperitoneal y for 12 weeks. Myocardial injury indices and oxidative stress markers were determined. Changes in cardiac ultrastructure were evaluated with transmission electron microscopy. Myocardial apoptosis was assessed via terminal deoxynucleotidyl transferase （TDT）-mediated DNA nick-end labeling （TUNEL） and immunohistochemistry. Ginsenoside Rg1 was as-sociated with a significant dose-dependent reduction in serum levels of creatinine kinase MB and cardiac troponin I, and lessened ultrastructural disorders in diabetic myocardium, relative to the untreated diabetic model rats. Also, compared with the untreated diabetic rats, significant reductions in serum and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1-treated groups, and increased levels of the antioxidants （superoxide dismutase, catalase, and glutathione peroxidase） were detected. TUNEL staining indicated reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be associated with reduced levels of caspase-3 （CASP3） and increased levels of B-cell lymphoma-extra-large （Bcl-xL） in the diabetic myocardium. Ginsenoside Rg1 treatment of diabetic rats was associated with reduced oxidative stress and attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of potential preventative and therapeutic value for cardiovascular injury in diabetic patients.
基金supported by research grants from the National Twelfth-Five Year Research Program of China (No.2012ZX093-01002001002)the National Natural Science Foundation of China (No.81473398)
文摘Ginsenoside Rg1(GR),a major bioactive compound of traditional Chinese medicine,such as Panax ginseng or Radix Notoginseng,has been shown to exert neuroprotective effects against ischemic stroke.However,pharmacokinetic studies have suggested that GR could not be efficiently transported through the blood–brain barrier.The mechanism by which GR attenuates cerebral ischemic injury in vivo remains largely unknown.Therefore,this study explored potential neuro-protective effects of GR through its systemic metabolic regulating mechanism by using mass spectrometry–based metabolomic profiling.Rats with middle cerebral artery occlusion(MCAO) were treated with GR intravenously.Their metabolic profiles in serum were measured by gas chromatography coupled with mass spectrometry on 1 and 3 days after MCAO.GR exhibited a potent neuro-protective effect by significantly decreasing the neurological scores and infarct volume in the MCAO rats.Moreover,18 differential metabolites were tentatively identified,all of which appeared to correlate well with these disease indices.Our findings suggested that GR carries a therapeutic potential in stroke possibly through a feed-back mechanism by regulating systematic metabolic mediation.
基金supported by the National Natural Science Foundation of China(Nos.81173578 and 81573493)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(No.Z141102004414062)+2 种基金National 863 Program of China(No.2014AA020803)the PUMC Youth Fund and Fundamental Research Funds for the Central Universities(No.3332015136)the Fundamental Research Funds for Central Public Institutes(No.2015CX12)
文摘Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry(LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile,urine, and feces after oral administration(25 mg/kg). Calibration curves offered satisfactory linearity(r40.995)within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1(Rh1), and protopanaxatriol(Ppt) in bile,urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile.Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.
基金supported by National Natural Science Foundation of China(81601034 and 31850410476)Anhui Provincial Science Fund for Distinguished Young Scholars(2008085J39,China)+5 种基金Focus on Research and Development Projects in Anhui Province(1804a0802225,China)State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(CMEMR2020B13,Guangxi Normal University,China)the Natural Science Foundation of Anhui Educational Committee(KJ2018ZD044 and KJ2020A0728,China)Key Disciplines of Pharmacy(2019xjzdxk2,China)the Back-up Candidates for Academic and Technical Leaders of Suzhou University(2018XJHB06,China)Key Research Project of Suzhou University(2019yzd06,China)。
文摘During the traumatic brain injury(TBI),improved expression of circulatory miR-21 serves as a diagnostic feature.Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and bloodebrain barrier(BBB)permeability,reduce nerve apoptosis,restore neural function and ameliorate TBI.We evaluated the role of macrophage derived exosomes-miR-21(M-Exos-miR-21)in disrupting BBB,deteriorating TBI,and Rg1 interventions.IL-1β-induced macrophages(ⅡA)-Exos-miR-21 can activate NF-kB signaling pathway and induce the expressions of MMP-1,-3 and-9 and downregulate the levels of tight junction proteins(TJPs)deteriorating the BBB.Rg1 reduced miR-21-5 p content in ⅡA-Exos(RⅡA-Exos).The interaction of NMIIAe HSP90 controlled the release of Exos-miR-21,this interaction was restricted by Rg1.Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain,enhancing TIMP3 protein expression,MMPs proteolysis,and restricting TJPs degradation thus protected the BBB integrity.Conclusively,Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.
基金the Natural Science Foundation of Hunan Province(Nos.2017JJ2338 and 2020JJ4860)the National Key Specialty Construction Project of Clinical Pharmacy(No.2013-5).
文摘Fufang Danshen preparation(FDP)is consisted of Salviae Miltiorrhizar Radix et Rhizoma(Danshen),Notoginseng Radix et Rhizoma(Sanqi)and Borneolum Syntheticum(borneol).FDP is usually used to treat myocardial ischemia hypoxia,cerebral ischemia and alzheimer’s disease,etc.In the treatment of cerebrovascular diseases,borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs,especially to the brain.The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA(TS IIA),salvianolic acid B(SAB)and ginsenoside Rg1 in FDP.Male healthy Sprague-Dawley(SD)rats were given Danshen extracts,Sanqi extracts(Panax notoginseng saponins)or simultaneously administered Danshen extracts,Sanqi extracts and borneol.Plasma and brain samples were collected at different points in time.The concentration of TS IIA,SAB and Rg1 was determined by UPLC-MS/MS method.The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software.In comparison with Danshen and Sanqi alone,there were significant differences in pharmacokinetic parameters of TS IIA,SAB and Rg1,and the brain distribution of SAB and TS IIA when Danshen,Sanqi and borneol were administrated together.Borneol statistically significant shortened tmax of TS IIA,SAB and Rg1 in plasma and brain,increased the bioavaiability of Rg1,inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain.These results indicated that borneol could affect the multiple targets components and produce synergistic effects.Through accelerating the intestinal absorption and brain distribution,borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.
基金This study was supported by the National Health Research Institutes(BN-109-PP-01)National Health Research Institutes and Central Government S&T grant,Taiwan(109-1901-01-19-07)subsidized by Ministry of Science and Technology and National Taiwan University(NTU),Taiwan.
文摘Many technologies have been developed for breast reconstruction after lumpectomy.Although the technologies achieved promising success in clinical,there are still many shortages hanging over and trouble the researchers.Tissue engineering technology was introduced to plastic surgery that gave a light to lumpectomy patients in breast reconstruction.The unexpected absorption rate,resulting from limited vascularization and low cell survival rate,is a major factor that leads to unsatisfactory results for the previous studies in our lab.In the study,the laminin-modified alginate synthesized by a new method of low concertation of sodium periodate would be mixed with ADSCs and Rg1 in the medium;and then sprayed into a calcium chloride(CaCl2)solution to prepare into microsphere(abbreviated as ADSC-G-LAMS)by bio-electrospray with a power syringe for the mass production and smaller bead size.The developed ADSC-G-LAMS microspheres had the diameter of 232±42μm.Sustained-release of the Rg1 retained its biological activity.WST-1,live/dead staining,and chromosome aberration assay were evaluated to confirm the safety of the microspheres.In in vivo study,ADSC-G-LAMS microspheres combined with autologous adipocytes were transplanted into the dorsum of rats by subcutaneous injection.The efficacy was investigated by H&E and immunofluorescence staining.The results showed that the bioactive ADSC-G-LAMS microspheres could integrate well into the host adipose tissue with an adequate rate of angiogenesis by constantly releasing Rg1 to enhance the ADSC or adipocyte survival rate to join tissue growth and repair with adipogenesis for breast reconstruction after lumpectomy.
