Protective effects of ginsenosides Rg1 and Rb1 against cognitive impairment induced by simulated microgravity in rats / 中国药理学与毒理学杂志

OBJECTIVE Microgravity exerts several negative effects on the learning and memory of astro-nauts during space flight.Rg1 and Rb1,the key steroidal components of ginseng,have shown potent neuroprotec-tive effects with a high safety profile.The object of the current study is to investigate the influence of Rg1 and Rb1 on simulated microgravity-induced memory and learning dysfunction in the hindlimb suspension(HLS)rat model.METHODS The HLS rats were orally administered Rg1(30 and 60 μmol·kg-1)or Rb1(30 and 60 μmol·kg-1)for four weeks.The Morris water maze test(MWM)and reward operating conditioning reflex test(ROCR)were conducted to evaluate spatial and associative learning and memory.After the behavior tests,the serum and the prefrontal cortex(PFC)were dissected to measure the mechanism.RESULTS Rg1 and Rb1 treatment amelio-rated the cognitive deficits of HLS-exposure rats in MWM and ROCR,reduced reactive oxygen species generation and increased antioxidant enzyme activity.Rg1 and Rb1 also assisted in the recovery of mitochondrial complex Ⅰ(NADH dehydrogenase)activities and Mfn2,and decrea-sed Drp-1 expression.Furthermore,Rg1 and Rb1 reduced the ratio of Bax/Bcl-2 and the expression of cleaved-cas-pase 3,cytochrome c,increased the levels of SYN,PSD95 and activated BDNF-TrkB/PI3K-Akt pathway in the PFC.CONCLUSION Rg1 and Rb1 treatment attenuated cog-nitive deficits induced by HLS,mitigated mitochondrial dysfunction,attenuated oxidative stress,inhibited apopto-sis,and increased the synaptic plasticity,which was partly mediated by the modulation of the BDNF-TrkB/PI3K-Akt signaling.

Ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 for the treatment of primary retinitis pigmentosa / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 on serum brain-derived neurotrophic factor(BDNF), pituitary adenylate cyclase activating polypeptide(PACAP)and clinical efficacy in primary retinitis pigmentosa.METHODS: A total of 50 patients(100 eyes)with primary retinitis pigmentosa who admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Hebei North University from August 2019 to March 2022 were selected as the research object. They were divided into the study group and the control group according to random number table, with 50 eyes in each group. Patients in the control group were treated with inosine tablets and vitamin B1, while patients in the study group were treated with ginsenoside Rg1 injection on the basis of the control group. The expression of BDNF and PACAP in serum, electroretinogram and spectral-domain optical coherence tomography(SD-OCT)were compared before and after treatment, and the retinal thickness(RT), mean deviation(MD), clinical efficacy and safety indexes were compared between the two groups.RESULTS: There were no differences in the MD of the two groups before treatment(t=1.670, P=0.098), while the MD of the study group was significantly lower than that of the control group after treatment(t=3.628, P<0.01). Before treatment, RT with a diameter of 1mm at the circle of macular fovea was compared between the two groups(t=0.108, P=0.914), it was significantly higher than that in the control group after treatment(t=6.125, P<0.01). Before treatment, there was no significant difference in the results of dark adaptation of electroretinogram between the two groups(all P>0.05). After treatment, the results of dark adaptation in the study group were significantly better than those in the control group(all P<0.01). Before treatment, there was no significant difference in the results of electroretinogram adaptation between the two groups(all P>0.05). After treatment, the results of electroretinogram adaptation in the study group were significantly better than those in the control group(all P<0.01). There was no significant difference in BDNF and PACAP between the two groups before treatment(all P>0.05). BDNF and PACAP in the study group were higher than those of the control group after treatment(all P<0.01). After treatment, no adverse reactions were observed in both groups.CONCLUSION: The treatment of patients with primary retinitis pigmentosa with ginsenoside will improve the retinal function and promote the prognosis of the disease by regulating the expression of BDNF and PACAP, and it is highly safe.

Progress on the neuroprotective effects of ginsenoside Rg1 / 药学学报

Ginsenoside Rg1 is one of the most important saponins in ginseng. It has a wide range of pharmacological activities. It is considered to be a powerful neuroprotective agent. It has neuroprotective effects such as anti-neuroinflammation, anti-oxidative stress, anti-neuronal apoptosis, and enhancing memory. Rg1 shows a good application prospect in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, and mental diseases such as depression. This paper reviews the research on the neuroprotective mechanism of Rg1 at home and abroad in recent years, in order to provide new research ideas for the clinical treatment of nervous system diseases.

Functionalized exosome-loaded ginsenoside Rg1 for the treatment of ischemic stroke / 生物工程学报

The aim of this study was to investigate the therapeutic effects and potential mechanism of c(RGDyK) peptide modified mesenchymal stem cell exosomes loaded with ginsenoside Rg1 (G-Rg1) on ischemic stroke. Thread-tying method was used to establish SD rats transient middle cerebral occlusion model (tMCAO). The model rats were randomly divided into tMCAO group, Exo group, free G-Rg1 group, Exo-Rg1 group and cRGD-Exo-Rg1 group, and sham group was used as control. The infarct volume was measured by 2, 3, 5-triphenyltetrachloride (TTC) staining, the changes of neuron and endothelium were observed by immunofluorescence, and the expression of related proteins was detected by Western blotting. The results showed that cRGD-Exo-Rg1 up-regulated the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF-1α) by activating PI3K/AKT pathway, thus promoting angiogenesis and neurogenesis, effectively reducing the volume of cerebral infarction and improving neural function. In addition, the delivery of cRGD-Exo-Rg1 to ischemic brain tissue up-regulated the expression of occludin and claudin-5, and reduced the injury of blood-brain barrier. Taken together, cRGD-Exo-Rg1 was effective in the treatment of ischemic stroke by promoting angiogenesis and neurogenesis, which provided experimental evidence for the potential clinical benefits of other neuroprotective therapies.

Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway / 中国天然药物

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).

Molecular mechanism of ginsenoside Rg_1 against radiation enteritis: based on network pharmacology and in vitro experiment / 中国中药杂志

Via network pharmacology, molecular docking, and cellular experiment, this study explored and validated the potential molecular mechanism of ginsenoside Rg_1(Rg_1) against radiation enteritis. Targets of Rg_1 and radiation enteritis were retrieved from BATMAN-TCM, SwissTargetPrediction, and GeneCards. Cytoscape 3.7.2 and STRING were employed for the construction of protein-protein interaction(PPI) network for the common targets, and screening of core targets. DAVID was used for Gene Ontology(GO) term and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict the possible mechanism, followed by molecular docking of Rg_1 with core targets and cellular experiment. For the cellular experiment, ~(60)Co-γ irradiation was performed for mo-deling of IEC-6 cells, which were then treated with Rg_1, protein kinase B(AKT) inhibitor LY294002, and other drugs to verify the effect and mechanism of Rg_1. The results showed that 29 potential targets of Rg_1, 4 941 disease targets, and 25 common targets were screened out. According to the PPI network, the core targets were AKT1, vascular endothelial growth factor A(VEGFA), heat shock protein 90 alpha family class A member 1(HSP90AA1), Bcl-2-like protein 1(BCL2L1), estrogen receptor 1(ESR1), etc. The common targets were mainly involved in the GO terms such as positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, positive regulation of cell proliferation, and other biological processes. The top 10 KEGG pathways included phosphoinositide 3-kinase(PI3K)/AKT pathway, RAS pathway, mitogen-activated protein kinase(MAPK) pathway, Ras-proximate-1(RAP1) pathway, and calcium pathway, etc. Molecular docking showed that Rg_1 had high binding affinity to AKT1, VEGFA, HSP90AA1, and other core targets. Cellular experiment indicated that Rg_1 can effectively improve cell viability and survival, decrease apoptosis after irradiation, promote the expression of AKT1 and B-cell lymphoma-extra large(BCL-XL), and inhibit the expression of the pro-apoptotic protein Bcl-2-associated X protein(BAX). In conclusion, through network pharmacology, molecular docking, and cellular experiment, this study verified the ability of Rg_1 to reduce radiation enteritis injury. The mechanism was that it regulated PI3K/AKT pathway, thereby suppressing apoptosis.

Ginsenoside Rg_1 protects PC12 cells against Aβ-induced injury through promotion of mitophagy by PINK1/parkin activation / 中国中药杂志

Amyloid β-protein(Aβ) deposition in the brain is directly responsible for neuronal mitochondrial damage of Alzheimer's disease(AD) patients. Mitophagy, which removes damaged mitochondria, is a vital mode of neuron protection. Ginsenoside Rg_1(Rg_1), with neuroprotective effect, has displayed promising potential for AD treatment. However, the mechanism underlying the neuroprotective effect of Rg_1 has not been fully elucidated. The present study investigated the effects of ginsenoside Rg_(1 )on the autophagy of PC12 cells injured by Aβ_(25-35) to gain insight into the neuroprotective mechanism of Rg_1. The autophagy inducer rapamycin and the autophagy inhi-bitor chloroquine were used to verify the correlation between the neuroprotective effect of Rg_1 and autophagy. The results showed that Rg_1 enhanced the viability and increased the mitochondrial membrane potential of Aβ-injured PC12 cells, while these changes were blocked by chloroquine. Furthermore, Rg_(1 )treatment increased the LC3Ⅱ/Ⅰ protein ratio, promoted the depletion of p62 protein, up-regulated the protein levels of PINK1 and parkin, and reduced the amount of autophagy adaptor OPTN, which indicated the enhancement of autophagy. After the silencing of PINK1, a key regulatory site of mitophagy, Rg_1 could not increase the expression of PINK1 and parkin or the amount of NDP52, whereas it can still increase the LC3Ⅱ/Ⅰ protein ratio and promote the depletion of OPTN protein which indicated the enhancement of autophagy. Collectively, the results of this study imply that Rg_1 can promote autophagy of PC12 cells injured by Aβ, and may reduce Aβ-induced mitochondrial damage by promoting PINK1-dependent mitophagy, which may be one of the key mechanisms of its neuroprotective effect.

Protective effect of ginsenoside Rg_1 aganist diabetic retinopathy by inhibiting NLRP3 inflammasome in type 2 diabetic mice / 中国中药杂志

Ginsenoside Rg_1, one of the main active components of precious traditional Chinese medicine Ginseng Radix et Rhizoma, has the anti-oxidative stress, anti-inflammation, anti-aging, neuroprotection, and other pharmacological effects. Diabetic retinopathy(DR), the most common complication of diabetes, is also the main cause of impaired vision and blindness in the middle-aged and the elderly. The latest research shows that ginsenoside Rg_1 can protect patients against DR, but the protection and the mechanism are rarely studied. This study mainly explored the protective effect of ginsenoside Rg_1 against DR in type 2 diabetic mice and the mechanism. High fat diet(HFD) and streptozotocin(STZ) were used to induce type 2 diabetes in mice, and hematoxylin-eosin(HE) staining was employed to observe pathological changes in the retina of mice. The immunohistochemistry was applied to study the localization and expression of nucleotide-binding oligomerization domain-like receptors 3(NLRP3) and vascular endothelial growth factor(VEGF) in retina, and Western blot was used to detect the expression of nuclear factor-kappa B(NF-κB), p-NF-κB, NLRP3, caspase-1, interleukin-1β(IL-1β), transient receptor potential channel protein 6(TRPC6), nuclear factor of activated T-cell 2(NFAT2), and VEGF in retina. The results showed that ginsenoside Rg_1 significantly alleviated the pathological injury of retina in type 2 diabetic mice. Immunohistochemistry results demonstrated that ginsenoside Rg_1 significantly decreased the expression of NLRP3 and VEGF in retinal ganglion cells, middle plexiform layer, and outer plexiform layer in type 2 diabetic mice. According to the Western blot results, ginsenoside Rg_1 significantly lowered the expression of p-NF-κB, NLRP3, caspase-1, IL-1β, TRPC6, NFAT2, and VEGF in retina of type 2 diabetic mice. These findings suggest that ginsenoside Rg_1 can significantly alleviate DR in type 2 diabetic mice, which may be related to inhibition of NLRP3 inflammasome and VEGF. This study provides experimental evidence for the clinical application of ginsenoside Rg_1 in the treatment of DR.

Quality evaluation of ginsenoside reference substances based on qNMR spectroscopy / 中国中药杂志

The present study established a quality evaluation method for ginsenoside reference substances based on quantitative nuclear magnetic resonance(qNMR) spectroscopy. ~1H-NMR spectra were collected on Bruker Avance Ⅲ 500 MHz NMR spectrometer equipped with a 5 mm BBO probe. The acquire parameters were set up as follows: pulse sequence of 30°, D_1=20 s, probe temperature= 303 K, and the scan number = 32. Dimethyl terephthalate, a high-quality ~1H-qNMR standard, was used as the internal standard and measured by the absolute quantitative method. Methyl peaks of comparatively good sensitivity were selected for quantification, and linear fitting deconvolution was adopted to improve the accuracy of integration results. The qNMR spectroscopy-based method was established and validated, which was then used for the quality evaluation of ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, ginsenoside Rd, and notoginsenoside R_1. The results suggested that the content of these ginsenoside reference standards obtained from the qNMR spectroscopy-based method was lower than that detected by the normalization method in HPLC provided by the manufacturers. In conclusion, the qNMR spectroscopy-based method can ensure the quality of ginsenoside reference substances and provide powerful support for the accurate quality evaluation of Chinese medicine and its preparations. The qNMR spectroscopy-based method is simple, rapid, and accurate, which can be developed for the quantitative assay of Chinese medicine standard references.

Effect of Ginsenoside Rg1 on Biological Activity of Cryopreserved Schwann Cells and Nerve Regeneration After Allograft in Rat Sciatic Nerve / 中国实验方剂学杂志

ObjectiveTo observe the effect of ginsenoside Rg1 （G-Rg1） on the biological activity of cryopreserved Schwann cells （SCs） of the rat sciatic nerve and explore the feasibility of G-Rg1 in reducing the cryopreservation-induced injury in SCs. MethodBilateral sciatic nerves of SD rats were randomly divided into a fresh group， a blank group， and five G-Rg1 groups of different doses （1×10-7， 1×10-6， 1×10-5， 1×10-4， and 1×10-3 mol·L-1）. The nerves in the blank group and the G-Rg1 groups were preserved in liquid nitrogen solutions containing 0， 1×10-7， 1×10-6， 1×10-5， 1×10-4， and 1×10-3 mol·L-1 G-Rg1 for four weeks. The apoptosis of SCs was detected by TdT-mediated dUTP-biotin nick end labeling （TUNEL）/S100 immunofluorescence staining. The expression of cysteinyl aspartate-specific protease （Caspase）-9， Caspase-3， major histocompatibility complex （MHC）-Ⅰ， and MHC-Ⅱ was detected by Western blot. Subsequently， all nerves were cultured in the incubator at 37 ℃ with 5% CO2 for 7 days. The expression of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF） was detected by Western blot. In addition， the above cryopreserved nerves in the blank group and the 1×10-6， 1×10-5， and 1×10-4 mol·L-1 G-Rg1 groups were transplanted to the Wistar rats by allografting （blank transplantation group and the 1×10-6， 1×10-5， and 1×10-4 mol·L-1 G-Rg1 transplantation groups）， and fresh sciatic nerve allograft and isograft control group were set up. Sixteen weeks after transplantation， compound muscle action potential （CMAP） and nerve conduction velocity （NCV） were measured by electrophysiology. Nerve filament （NF）200 immunofluorescence staining， transmission electron microscopy， and toluidine blue staining were used to analyze the histology of the regenerated nerves. ResultCompared with the fresh group， the blank group and the G-Rg1 groups showed increased expression of Caspase-9， Caspase-3， and the apoptosis of SCs （P<0.05，P<0.01） and decreased expression of GDNF， NGF， MHC-Ⅰ， and MHC-Ⅱ （P<0.01）. Compared with the results in the blank group， the expression of Caspase-9 and Caspase-3 decreased in the 1×10-7， 1×10-6， 1×10-5，1×10-4 mol·L-1 G-Rg1 groups （P<0.01）， and the apoptosis of SCs was reduced in the 1×10-7-1×10-4 mol·L-1 G-Rg1 groups（P<0.05，P<0.01） and increased in the 1×10-3 mol·L-1 group （P<0.05）， while the expression of GDNF and NGF increased in the 1×10-7， 1×10-6， 1×10-5，1×10-4 mol·L-1 G-Rg1 groups and decreased in the 1×10-3 mol·L-1 group （P<0.05）. There was no statistical significance in the expression of MHC-Ⅰ and MHC-Ⅱ between the blank group and the G-Rg1 groups. Compared with the 1×10-7 mol·L-1 and 1×10-3 mol·L-1 G-Rg1 groups， the 1×10-6 1×10-5， 1×10-4 mol·L-1 G-Rg1 groups showed decreased expression of Caspase-3 and the apoptosis of SCs （P<0.05，P<0.01） and increased expression of GDNF and NGF （P<0.05，P<0.01）. There was no statistical significance in MHC-Ⅰ and MHC-Ⅱ expression among G-Rg1 groups. Sixteen weeks after transplantation， compared with the isograft group， the blank transplantation group and the G-Rg1 transplantation groups showed decreased CMAP， NCV， myelin sheath thickness， and number of myelinated nerve fibers （P<0.01）， and the 1×10-6 and 1×10-4 mol·L-1 G-Rg1 transplantation groups showed decreased NF200 （P<0.01）. Compared with the allograft group， the blank transplantation group and the G-Rg1 transplantation groups showed increased CMAP， NCV， NF200， myelin sheath thickness， and number of myelinated nerve fibers （P<0.05，P<0.01）. Compared with the blank transplantation group， the G-Rg1 transplantation groups showed increased CMAP， NCV， NF200， myelin sheath thickness， and number of myelinated nerve fibers （P<0.05，P<0.01）. Among all groups of G-Rg1 transplantation， each index of the 1×10-5 mol·L-1 G-Rg1 transplantation group was superior to that of the 1×10-4 and 1×10-6 mol·L-1 G-Rg1 transplantation group （P<0.05）. ConclusionG-Rg1 at a certain centration can maintain the biological activity of cryopreserved SCs of rat sciatic nerve， alleviate the cryopreservation-induced injury of rat sciatic nerve， and promote nerve regeneration after allograft.

Protective Effect of Ginsenosides Rg1 and Rb1 Against Intestinal Epithelial Barrier Injury Induced by Lipopolysaccharide in Vitro / 中国实验方剂学杂志

ObjectiveTo investigate the effects of ginsenoside Rg1 and ginsenoside Rb1 on the release of inflammatory factors of human myeloid leukemia monocytes （THP-1） induced by lipopolysaccharide （LPS） and their protective effects on the inflammatory injury of intestinal epithelial cells （Caco-2） induced by THP-1 cell activation based on the co-culture system of THP-1 and Caco-2. MethodFirstly，the microfluidic chip of co-culture of THP-1 and Caco-2 cells was prepared. In the experiment， a blank group， an LPS group， and drug intervention groups were set up.The cells in the blank group were cultured conventionally. In the LPS group，LPS （1 mg·L-1） was added to the lower THP-1 cells after the upper Caco-2 cells formed a monolayer barrier. On the basis of the LPS group， 33 mg·L-1 ginsenoside Rg1 and 33 mg·L-1 ginsenoside Rb1 were added to THP-1 cells respectively. After the co-culture of THP-1 cells and Caco-2 cells for 24 hours， the fluorescein isothiocyanate （FITC）-Dextran fluorescence value in the lower chip channel was detected by FITC-Dextran tracer method. A blank group， an LPS group，and drug intervention groups were set up in the THP-1 cell experiment. THP-1 cells in the blank group were cultured conventionally. In the LPS group， LPS （1 mg·L-1） was added to THP-1 cells.Ginsenoside Rg1 and ginsenoside Rb1 of the corresponding doses （11，33，100 mg·L-1） were added to the drug intervention groups respectively on the basis of the LSP group. After 24 hours of cell culture， the activity of THP-1 cells was detected by cell counting kit-8 （CCK-8）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression of inflammatory cytokines such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor （TNF）-α of THP-1 cells. A blank group， an LPS group， and drug intervention groups were set up in the Caco-2 cell experiment. Caco-2 cells in the blank group were cultured conventionally， and in other groups， the corresponding cell supernatant in the second part of the THP-1 cell experiment was employed in Caco-2 cells. After 24 hours of cell culture，the activity of Caco-2 cells was detected by CCK-8. Real-time PCR was used to detect the expression of IL-6，interleukin-8 （IL-8）， TNF-α， and Occludin of Caco-2 cells. The expression of tight junction protein Occludin in Caco-2 cells was detected by Western blot. ResultBoth ginsenoside Rg1 and ginsenoside Rb1 could effectively protect LPS-induced intestinal epithelial barrier permeability in the co-culture system of THP-1 and Caco-2 cells （P<0.01）. Ginsenosides Rg1 and Rb1 antagonized LPS-induced increased expression of IL-6，IL-1β， and TNF-α in THP-1 cells （P<0.05）. When the supernatant of THP-1 cells treated with ginsenosides Rg1 and Rb1 was co-cultured with Caco-2 cells， the expression of IL-6，IL-8， and TNF-α in Caco-2 cells was significantly reduced （P<0.01）， and the expression of tight junction protein Occludin was up-regulated. ConclusionIn the co-culture system of THP-1 and Caco-2 cells simulating the intestinal epithelial barrier function in vitro，ginsenosides Rg1 and Rb1 play a protective role against LPS-induced intestinal epithelial barrier injury by regulating the release of inflammatory cytokines by THP-1 cells， thereby regulating the inflammatory response and cell barrier integrity of Caco-2 cells.

Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro / 中国结合医学杂志

OBJECTIVE@#To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.@*METHODS@#The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined.@*RESULTS@#For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs.@*CONCLUSION@#Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].

Protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation injury and its mechanism / 中国中药杂志

This project aimed to explore the protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation(H/R)-induced H9 c2 cardiomyocyte injury and its underlying signaling pathway. The H/R model of H9 c2 cardiomyocytes was established and then the cells were divided into different treatment groups. CCK-8(cell counting kit-8) was used to detect the activity of cardiomyocytes; Brdu assay was used to detect the proliferation of H9 c2 cells; the caspase-3 activity was tested, and then the protein expression was assessed by Western blot. Flow cytometry was used to evaluate the apoptosis level of cardiomyocytes. Ginsenoside Rg_1 inhibited H/R-induced cardiomyocyte apoptosis and caspase-3 activity, promoted nuclear transcription of nuclear factor erythroid-2 related factor 2(Nrf2), and enhanced the expression of the downstream heme oxygenase-1(HO-1). Ginsenoside Rg_1 could increase Nrf2 nuclear transcription and HO-1 expression with the increase of concentration(10, 20, 40, 60 μmol·L~(-1)). However, the protective effect of ginsenoside Rg_1 on cardiomyocytes was significantly weakened after the transfection of Nrf2-siRNA. Ginsenoside Rg_1 could protect cardiomyocytes by activating the Nrf2/HO-1 pathway.

Research advances on the effect of ginsenoside Rg1 on angiogenesis and vascular protection / 药学学报

Ginsenoside Rg1 is one of the most important active components of the "king of herbs" Panax ginseng, which is an important angiogenic protective agent. The research results have shown that Rg1 has a wide range of cardiovascular pharmacological effects in vivo and in vitro, mainly through promoting the proliferation of smooth muscle cells, inhibiting endothelial cell aging, antioxidant stress, inhibiting inflammatory response, activating key factors of angiogenesis, improving vasodilation and other ways. Many miRNAs participate in the process of Rg1 promoting angiogenesis, mediate the regulation of the specific expression of downstream related targets to promote angiogenesis and vascular remodeling, and have the potential to become new clinical biomarkers and therapeutic targets. New preparation technologies and materials are used to make up for the weakness of Rg1's blood-brain barrier permeability, and further promote and enrich the clinical application of Rg1.

The effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA, salvianolic acid B and ginsenoside Rg / 中国天然药物

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 notoginsengsaponins) or simultaneously administered Danshenextracts, 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 t

Ginsenoside Rg1 ameliorates blood-brain barrier disruption and traumatic brain injury

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 blood-brain 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-1

Effect of ginsenoside Rg_1 in delaying premature ovarian failure induced by D-gal in mice through PI3K/Akt/mTOR autophagy pathway / 中国中药杂志

The aim of this paper was to study the role of phosphoinositide 3-kinase(PI3 K), protein kinase B(Akt) and mamma-lian target of rapamycin(mTOR) in the inhibition of premature ovarian failure induced by D-galactose(D-gal) in mice model by ginsenoside Rg_1(Rg_1). Fifty-four female SPF BALB/c mice were randomly divided into PBS group, D-gal group, and Rg_1 group. In the D-gal group, D-galactose(200 mg·kg~(-1)·d~(-1)) was injected subcutaneously into the neck and back for 42 days. In the PBS group, an equal amount of phosphate buffered saline(PBS) was injected into the neck and back for 42 days. In addition to the therapy of D-gal group, Rg_1 group was given Rg_1(20 mg·kg~(-1)·d~(-1)) through intraperitoneal injection since the 15 th day for 28 days, at the same time, the D-gal group and the PBS group were also given an equal amount of PBS through intraperitoneal injection since the 15 th day for 28 days. After the treatment, the estrous cycle changes of the mice were detected, and the ovarian SA-β-Gal staining was used to detect the changes of ovarian aging. Western blot was used to detect the changes in protein expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). Fluorescence quantitative PCR was used to detect the changes in mRNA expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). According to the findings, compared with the PBS group, the D-gal group began to show estrous cycle disorder in the 3 rd week,the ovarian SA-β-Gal staining positive granulosa cells increased in the D-gal group, the expression of senescence marker P16~(INK4 a) increased, while the expression of autophagy signaling molecule LC3-Ⅱ decreased. After treatment with Rg_1, the positive rate of ovarian SA-β-Gal staining in Rg_1 group decreased, the expression level of autophagy signaling molecule LC3-Ⅱ in Rg_1 group was higher than that in D-gal group, while the expression level of senescence marker P16~(INK4 a) was lower than that in D-gal group. Compared with the PBS group, the protein and mRNA expressions of PI3 K, Akt, mTOR and S6 k in the D-gal group were up-regulated, the protein expressions of Akt, mTOR and S6 k in the Rg_1 group were up-regulated, and the mRNA expressions of PI3 K and mTOR were up-regulated. After treatment with Rg_1, the protein expressions of PI3 K, Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group, while the mRNA expressions of Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group. The finding ssuggested that Rg_1 has the effect in delaying ovarian premature failure in D-gal-induced mouse models, and PI3 K/Akt/mTOR autophagy signaling pathways play an important role.

Ginsenoside Rg1 in the treatment of nonalcoholic fatty liver disease / 中国临床药理学与治疗学

Nonalcoholic fatty liver (NAFLD) is a substantial pathological change of the liver caused by no excessive alcohol intake or genetic predisposition. It can further develop into non-alcoholic steatohepatitis, liver cirrhosis, hepatocellular carcinoma, liver failure. Studies have shown that non-alcoholic fatty liver is also closely related to a variety of metabolic diseases, such as type 2 diabetes mellitus(T2DM), hypertension, cardiovascular disease and so on. However, its pathogenesis is not clear, and there is a lack of drugs for clinical treatment. Ginsenoside Rg1 has a wide range of effects, such as antioxidation, anti-aging, anti-inflammatory reaction, auxiliary treatment of diabetes and so on. In this paper, the pathogenesis of NAFLD and the research progress of Rg1 in NAFLD are reviewed.

Ginsenoside Rg1 protects HL-7702 cells against oleic acid-induced injury via aldolase/AMPK/PINK1 signalling / 中国临床药理学与治疗学

AIM: To study the protective effects of ginsenoside Rg1 on HL-7702 cells injury induce by oleic acid (OA), and investigate its role in aldolase/AMPK/PINK1 signalling. METHODS: HL-7702 cells were cultured in vitro and divided into five groups: control group (C), oleic acid group (OA), OA+ginsenoside (Rg1) group, OA+compound C (CC) group, and OA+CC+Rg1 group. The viability of HL-7702 cells was determined by CCK8 assay and Hoechst staining. The apoptosis and mitochondrial membrane potentials of HL-7702 cells were measured using flow cytometry. ATP content in HL-7702 cells was observed. Western blot was used to detect the expression levels of Cleaved caspase-3, PINK1, MFN2, Aldolase and p-AMPK in HL-7702 cells. RESULTS:Compared with C group, the viability of cells in OA group was significantly decreased (P<0.05), the apoptotic rate and Cleaved caspase-3 expression were greatly increased (P<0.05), ATP level, mitochondrial membrane potentials (TMRE) and PINK1 expression were significantly decreased (P<0.05). Compared with OA group, the viability of cells in OA+Rg1 group was significantly increased (P<0.05), the apoptotic rate and Cleaved caspase-3 expression were greatly decreased (P<0.05), ATP level, mitochondrial membrane potentials (TMRE) and PINK1 expression were significantly increased (P<0.05). Compared with OA+Rg1 group, the viability of cells and p-AMPK expression level in OA+CC+Rg1 group was significantly decreased (P<0.05). Reducing the expression of aldolase in cells inhibited Rg1?s actions on PINK1 and p-AMPK and cell viability. CONCLUSION: Ginsenoside Rg1 can improve the injury of HL-7702 cells via regulating aldolase/AMPK/PINK1 signaling pathway.

Regulatory effect and mechanism of ginsenoside Rg1 on oxidative stress and inflammation in preeclampsia rats / 中国临床药理学与治疗学

AIM: To investigate the effect and mechanism of ginsenoside Rg1 on L-NAME-induced preeclampsia in rats. METHODS: All rats were divided into four groups: control group, model group, ginsenoside Rg1 low dose group (25 mg/kg) and high dose group (50 mg/kg). The rat model of preeclampsia was established by L-NAME induction. In the treatment group, the corresponding dose of ginsenoside Rg1 was given at the 5th day of pregnancy. On the 7th, 13th, 15th, 17th and 19th day, the systolic pressure, diastolic pressure and arterial pressure of the experimental rats in each group were examined, and 24-hour urine protein on the 20th day was measured. The experimental rats were killed on the 21st day and tissue samples were collected. The protein of GCM-1 was determined by immunohistochemistry, the activities of SOD and CAT, the levels of MDA, IL-1β, IL-6 and TNF-α in serum were determined by kit. Western blot was used to detect the expressions of Nrf2, HO-1, NF-κB, IκBα, Bcl-2, Bax, Caspase-3 and Cyt-c. RESULTS: The results showed that ginsenoside Rg1 could significantly improve the systolic pressure, diastolic pressure, arterial pressure and urinary protein (P<0.05), inhibit the expressions of GCM-1, Nrf2, HO-1, Bax, Caspase-3 and Cyt-c protein in placenta (P<0.05), increase the expressions of NF-κB, IκBα and Bcl-2 protein (P<0.05), and significantly promote the activities of SOD and CAT in serum and fetal tissue of model rats. The levels of MDA, IL-1β, IL-6 and TNF-α were inhibited (P<0.05). CONCLUSION: Rg1 can significantly improve the blood pressure and urinary protein level of pre-eclampsia pregnant rats, promote the expression of GCM-1 protein in placenta, inhibit oxidative stress injury and inflammatory response, and reduce apoptosis of placenta.