Effects Of Ginsenoside Rg1 Research Articles

Effects of ginsenoside Rg1 on HIF-1a, VEGF, and ET-1 expression in mice with chronic intermittent hypoxia and pain

Effects of ginsenoside Rg1 on HIF-1a, VEGF, and ET-1 expression in mice with chronic intermittent hypoxia and pain

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

Aplastic anemia (AA) presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells, with the current therapeutic options being notably limited. To assess the therapeutic potential of ginsenoside Rg1 on AA, specifically its protective effects, while elucidating the mechanism at play. We employed a model of myelosuppression induced by cyclophosphamide (CTX) in C57 mice, followed by administration of ginsenoside Rg1 over 13 d. The investigation 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. 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. 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.

Retracted: Effects of Ginsenoside Rg1 on the Biological Activity of Human Periodontal Ligament Cells.

[This retracts the article DOI: 10.1155/2022/7576359.].

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.

Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.

Reduction of alcohol-induced mitochondrial damage with ginsenoside Rg1 studied by atomic force microscopy

The quantification of mitochondrial morphology and mechanical properties is useful for the diagnosis and treatment of mitochondrial and alcoholic liver disease. In this study, the effects of ginsenoside Rg1 (G-Rg1) on the morphology and mechanical properties of mitochondria that had suffered alcohol-induced damage were investigated under near-physiological conditions. Additionally, the morphological and mechanical properties of mitochondria were quantified through atomic force microscopy. Atomic force microscopy revealed that alcohol-induced significant morphological changes in mitochondria. Compared with that of the mitochondria of normal hepatocytes, the average surface area of the damaged mitochondria was found to have increased significantly under the influence of alcohol. Furthermore, the mitochondrial area tended to be normal under the action of G-Rg1, whilst other parameters (length, width and perimeter) were significantly different from those of the mitochondria with the alcohol-induced damage. Simultaneously, alcohol significantly reduced the adhesion and elastic modulus of mitochondria, whilst the adhesion and elastic modulus of mitochondria in the G-Rg1 treatment group were closer to the values of normal mitochondria. This study overall showed that G-Rg1 could effectively alleviate the swelling and anomalous mechanical properties of mitochondria induced by alcohol.

Effects of Ginsenoside Rg1 on the Biological Behavior of Human Amnion-Derived Mesenchymal Stem/Stromal Cells (hAD-MSCs).

Ginsenoside Rg1 (Rg1) is purified from ginseng with various pharmacological effects, which might facilitate the biological behavior of human amnion-derived mesenchymal stem/stromal cells (hAD-MSCs). This study is aimed at investigating the effects of Rg1 on the biological behavior, such as viability, proliferation, apoptosis, senescence, migration, and paracrine, of hAD-MSCs. hAD-MSCs were isolated from human amnions. The effects of Rg1 on the viability, proliferation, apoptosis, senescence, migration, and paracrine of hAD-MSCs were detected by CCK-8, EdU, flow cytometry, SA-β-Gal staining, wound healing, and ELISA assays, respectively. The protein expression levels were detected by western blot. Cell cycle distribution was evaluated using flow cytometry. We found that Rg1 promoted hAD-MSC cycle progression from G0/G1 to S and G2/M phases and significantly increased hAD-MSC proliferation rate. Rg1 activated PI3K/AKT signaling pathway and significantly upregulated the expressions of cyclin D, cyclin E, CDK4, and CDK2 in hAD-MSCs. Inhibition of PI3K/AKT signaling significantly downregulated the expressions of cyclin D, cyclin E, CDK4, and CDK2, prevented cell cycle progression, and reduced hAD-MSC proliferation induced by Rg1. hAD-MSC senescence rate was significantly increased by D-galactose, while the elevated hAD-MSC senescence rate induced by D-galactose was significantly decreased by Rg1 treatment. D-galactose significantly induced the expressions of senescence markers, p16INK4a, p14ARF, p21CIP1, and p53 in hAD-MSCs, while Rg1 significantly reduced the expressions of those markers induced by D-galactose in hAD-MSCs. Rg1 significantly promoted the secretion of IGF-I in hAD-MSCs. Rg1 reduced the hAD-MSC apoptosis rate. However, the difference was not significant. Rg1 had no influence on hAD-MSC migration. Altogether, our results demonstrate that Rg1 can promote the viability, proliferation, and paracrine and relieve the senescence of hAD-MSCs. PI3K/AKT signaling pathway is involved in the promotive effect of Rg1 on hAD-MSC proliferation. The protective effect of Rg1 on hAD-MSC senescence may be achieved via the downregulation of p16INK4A and p53/p21CIP1 pathway.

Ginsenoside Rg1 modulates vesicular dopamine storage and release during exocytosis revealed with single-vesicle electrochemistry.

Ginsenoside Rg1, a tetracyclic triterpenoid derivative extracted from the roots of Panax ginseng C. A. Meyer, can enhance learning and memory and improve cognitive impairment. However, whether or how it affects vesicular dopamine storage and its release during exocytosis remains unknown. By using single-vesicle electrochemistry, we for the first time find out that Rg1 not only upregulates vesicular dopamine content but also increases exocytosis frequency and modulates dopamine release during exocytosis in PC12 cells, which may relate to the activation of protein kinases, causing a series of biological cascades. This finding offers the possible link between Rg1 and vesicular chemical storage and exocytotic release, which is of significance for understanding the nootropic role of Rg1 from the perspective of neurotransmission.

Ginsenoside Rg1 ameliorates chronic intermittent hypoxia-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway

BackgroundAs the major pathophysiological feature of obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) is vital for the occurrence of cardiovascular complications. The activation of calpain-1 mediates the production of endothelial reactive oxygen species (ROS) and impairs nitric oxide (NO) bioavailability, resulting in vascular endothelial dysfunction (VED). Ginsenoside Rg1 is thought to against endothelial cell dysfunction, but the potential mechanism of CIH-induced VED remains unclear. MethodsC57BL/6 mice and human coronary artery endothelial cells (HCAECs) were exposed to CIH following knockout or overexpression of calpain-1. The effect of ginsenoside Rg1 on VED, oxidative stress, mitochondrial dysfunction, and the expression levels of calpain-1, PP2A and p-eNOS were detected both in vivo and in vitro. ResultsCIH promoted VED, oxidative stress and mitochondrial dysfunction accompanied by enhanced levels of calpain-1 and PP2A and reduced levels of p-eNOS in mice and cellular levels. Ginsenoside Rg1, calpain-1 knockout, OKA, NAC and TEMPOL treatment protected against CIH-induced VED, oxidative stress and mitochondrial dysfunction, which is likely concomitant with the downregulated protein expression of calpain-1 and PP2A and the upregulation of p-eNOS in mice and cellular levels. Calpain-1 overexpression increased the expression of PP2A, reduced the level of p-eNOS, and accelerated the occurrence and development of VED, oxidative stress and mitochondrial dysfunction in HCAECs exposed to CIH. Moreover, scavengers of O2•−, H2O2, complex Ⅰ or mitoKATP abolished CIH-induced impairment in endothelial-dependent relaxation. ConclusionGinsenoside Rg1 may alleviate CIH-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.

Effects of Ginsenoside Rg1 on the Biological Activity of Human Periodontal Ligament Cells.

, Objective. To investigate the effect of ginsenoside Rg1 on the biological activity of primary cultured human periodontal ligament cells (PDLC). Methods. The effects of ginsenoside Rg1 on the proliferation activity, protein synthesis, and alkaline phosphatase (ALP) activity of primary cultured human periodontal ligament cells were investigated by thiazole blue (MTT) colorimetric method, Coomassie brilliant blue method, and enzyme kinetics method. The effect of ginsenoside Rg1 on cell cycle was detected by flow cytometry, and the cells were labeled with calcium ion-sensitive fluorescent probe Fluo3/AM, and the effect of ginsenoside Rg1 on intracellular free calcium concentration was detected by laser scanning confocal microscope. Results. Compared with the control group, the experimental groups of ginsenoside Rg1 at various concentrations could significantly promote cell proliferation, and the effect time was the longest in the concentration range of 0.01-0.05 μmol/L;, Rg1 0.01umol/L and 0.05umol/L. The protein content in the 72-hour cell culture medium of the μmol/L group was significantly higher than that of the control group; the ALP activity in the 72-hour cell culture medium of the Rg1 0.01 μmol/L, 0.05 μmol/L, and 0.1 μmol/L groups was significantly higher than that of the control group; FCM assay showed that after 0.1 μmol/L Rg1 for 48 hours, compared with the control group, the proportion of cells in the early stage of DNA synthesis (G1%) of PDLC was significantly reduced, while the proportion of cells in the DNA synthesis stage (S%) and the value of cell proliferation index PrI (S + G2M)% were significantly increased; Rg1 increased intracellular calcium in PDLC cells at first and then decreased and finally maintained at a slightly higher resting calcium level than before drug addition. Conclusion. Ginsenoside Rg1 can increase the proliferation activity, protein synthesis, and alkaline phosphatase activity of periodontal ligament cells within a certain concentration range; Rg1 reduces the cells in G1 phase and increases cells in S phase of periodontal ligament fibroblasts. Change the concentration of free calcium ions in cells and promote more cells to enter a proliferative state.

Cerebroprotective Effects of Ginsenoside Rg1 on Rats with Amyloid β -Protein Induced Alzheimer’s Disease

Cerebroprotective Effects of Ginsenoside Rg1 on Rats with Amyloid β -Protein Induced Alzheimer’s Disease

The Effects of Ginsenoside Rg2 on Trastuzumab-Induced Cardiotoxicity

Ginsenoside Rg2 inhibited the deterioration of cardiac function in rats, ginsenoside Rg2 inhibited cardiomyocyte apoptosis, increased the expression of Caspase-3,Caspase-9 and BAX in cell experiment. Conclusions: Ginsenoside Rg2 could protect cardiomyocytes in TZM-induced toxicity and it might be via inhibiting cell apoptosis.

Effect of ginsenoside-Rg1 on experimental Parkinson's disease: A systematic review and meta-analysis of animal studies.

Previous studies have reported that ginsenoside-Rg1 (G-Rg1) was able to mitigate the loss of dopaminergic neurons in animal models of Parkinson's disease (PD). The present study provided a systematic review and meta-analysis of preclinical studies to pool current evidence on the effect of G-Rg1 on neurogenesis in the treatment of PD. Eligible studies were identified through a search from six databases: PubMed, EMBASE, Web of Science, VIP, Chinese National Knowledge Infrastructure and the Wanfang database. Primary outcomes were tyrosine hydroxylase (TH)-positive cells in the nigra, Nissl staining-positive cells in the nigra, pole test time and dopamine (DA) levels in the striatum. A total of 18 eligible studies were identified, involving 343 animals. Of these, 13 reported a significant relationship between G-Rg1 and improved TH-positive cells in the nigra compared with the control group (P<0.00001). Furthermore, 3 studies reported a significant relationship between G-Rg1 and improved Nissl-positive cells in the nigra compared with the control group (P<0.00001). In addition, 4 studies reported a significant effect of G-Rg1 to reduce the total pole test time compared with that in the control group (P=0.001). A total of 3 studies indicated a significant association between G-Rg1 and improved DA levels in the striatum compared with the control group (P<0.00001). These results suggested that G-Rg1 has positive effects in attenuating damage in models of PD, and thus, it is a potential candidate neuroprotective drug for human PD.

Ginsenoside Rg1 reduces &beta;‑amyloid levels by inhibiting CD&Kappa;5‑induced PPAR&gamma; phosphorylation in a neuron model of Alzheimer's disease.

The accumulation of β-amyloid peptides (Aβ) in the brain is a hallmark of Alzheimer's disease (AD). Studies have indicated that ginsenoside Rg1, a primary component of ginseng (Panax ginseng), reduces brain Aβ levels in an AD model through peroxisome proliferator-activated receptor γ (PPARγ), thereby regulating the expression of insulin-degrading enzyme (Ide) and β-amyloid cleavage enzyme 1 (Bace1), which are PPARγ target genes. However, the effects of ginsenoside Rg1 on PPARγ remain unclear. Since cyclin-dependent kinase 5 (CDK5) mediates PPARγ phosphorylation in adipose tissue, this study aimed to investigate whether ginsenoside Rg1 regulates PPARγ target genes and reduces Aβ levels by inhibiting PPARγ phosphorylation through the CDK5 pathway. In the present study, a model of AD was established by treating primary cultured rat hippocampal neurons with Aβ1-42. The cells were pretreatment with ginsenoside Rg1 and roscovitine, a CDK5-inhibitor, prior to the treatment with Aβ1-42. Neuronal apoptosis was detected using TUNEL staining. PPARγ phosphorylation and protein expression levels of PPARγ, CDK5, IDE, BACE1, amyloid precursor protein (APP) and Aβ1-42 were measured by western blotting. The mRNA expression levels of PPARγ, CDK5, IDE, BACE1 and APP were assessed using reverse transcription-quantitative PCR. The results of the present study demonstrated that in an AD model induced by Aβ1-42, ginsenoside Rg1 significantly decreased CDK5 expression, inhibited PPARγ phosphorylation at serine 273, elevated IDE expression, downregulated BACE1 and APP expression, decreased Aβ1-42 levels and attenuated neuronal apoptosis. The CDK5 inhibitor, roscovitine, demonstrated similar effects. These results suggest that ginsenoside Rg1 has neuroprotective properties and has potential for use in the treatment of AD.

The effect of Ginsenoside Rg1 in hepatic ischemia reperfusion (I/R) injury ameliorates ischemia-reperfusion-induced liver injury by inhibiting apoptosis

Hepatic ischemia reperfusion (I/R) injury (HIRI) HIRI is a complex, multifactorial pathophysiological process and in liver surgery has been known to significantly affect disease prognosis, surgical success rates, and patient survival. Ginsenoside Rgl (Rgl) monomer is one of the main active ingredients of ginseng. Previous studies have demonstrated that Rgl exerts various pharmacological effects through several mechanisms including suppression of apoptosis-related proteins levels, downregulation of inflammatory mediators and as well as antioxidant, which effectively exerts an organ protective effect I/R-induced damage. However, the exact mechanisms of Rg1 on HIRI remain to be elucidated. In the present study, we investigated the protective effect of Rg1 on hepatic ischemia-reperfusion (I/R) injury (HIRI) and explored its underlying molecular mechanism. A rat warm I/R injury model in vivo and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated BRL-3A cell model in vitro were established after pretreating with Rg1(20 mg/kg). The results showed that Rg1 reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TUNEL staining showed that pretreated with Rg1 inhibited the apoptosis rate compared with the I/R group. Moreover, pretreated with Rg1 significantly reduced the expression of Cyt-C, Caspase-9 and Caspase-3 to inhibit the cell apoptosis. Flow cytometry analysis showed the MMP in the I/R group was significantly increased, whereas pretreated with Rg1 effectively stabilized the MMP compared with the I/R group. in vitro, the proliferation of BRL-3A cells was significantly decreased by the OGD/R treatment, while Rg1 effectively reversed this phenomenon. In addition, western blotting showed that the increase of Cyt-C, Caspase-9 and Caspase-3 was inhibited by H2O2. These observations suggest that Rg1 exerts the protective effect by inhibiting the CypD protein-mediated mitochondrial apoptotic pathway.

Effects of Ginsenoside Rg1 Regulating Wnt/β-Catenin Signaling on Neural Stem Cells to Delay Brain Senescence.

This is a study on the relationship between the protective effect of ginsenoside Rg1 on senescent neural stem cells and Wnt-β/catenin signaling pathway. Background. Recent studies have shown that overactivation of the Wnt/β-catenin signaling pathway is closely related to stem cell senescence. Whether Rg1 delays the senescence of NSCs is related to the regulation of this signaling pathway. Methods. The whole brain of Nestin-GFP transgenic newborn rat was extracted, and NSCs were extracted and cultured to P3 generation. The following indicators were detected: (1) NSC culture identification, (2) the effect of LiCl on the proliferation and survival rate of NSCs, (3) the effect of ginsenoside Rg1 on the proliferation and survival of NSCs, (4) the growth of NSCs in each group observed by an optical microscope, (5) the cell cycle of each group detected by flow cytometry, (6) the proliferative ability of each group detected by BrdU, (7) the fluorescence intensity of Nestin and Sox2 of NSCs in each group observed by a fluorescence microscope, (8) the positive rate of senescence staining analyzed by SA-β-Gal staining, (9) the localization of β-catenin in NSCs observed by laser confocal microscopy, and (10) the changes of the Wnt/β-catenin pathway-related proteins in each group detected by Western blotting. Results. LiCl activates the Wnt/β-catenin pathway and promotes mouse neural stem cell senescence. Ginsenoside Rg1 promotes proliferation of neural stem cells and inhibits Wnt/β-catenin pathway activation. Conclusions. LiCl can activate the Wnt/β-catenin signaling pathway of NSCs, and ginsenoside Rg1 can antagonize the senescence of NSCs caused by activation of the Wnt/β-catenin signaling pathway and delay brain aging.

Ginsenoside Rg1 ameliorates palmitic acid-induced insulin resistance in HepG2 cells in association with modulating Akt and JNK activity.

Hepatic insulin resistance can be induced by excess dietary intake of saturated fat. Ginsenoside Rg1 (GRg1), the major active ginsenoside enriched in tonic food ginseng, was reported to help alleviate liver diseases. In the present study, GRg1 was evaluated for its impact on palmitic acid (PA)-induced hepatic insulin resistance model in vitro. Insulin resistance in HepG2 cells was induced by 0.5 mM PA exposure for 24 h and then the effect of GRg1 on cellular glucose consumption was measured. Expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase) were analyzed by Western blot and quantitative real-time polymerase chain reaction. Activation of protein kinases and transcript factor was analyzed by measuring protein phosphorylation. The influence of GRg1 on reactive oxygen species (ROS) production in HepG2 was also examined. GRg1 reversed PA-induced decrease in glucose consumption of HepG2 cells by downregulating gluconeogenesis genes G6pase and PEPCK. GRg1 increased Akt activation but inhibited JNK activation in PA-challenged HepG2 cells. Cellular ROS level was elevated in insulin-resistant HepG2 cells but was reduced by GRg1. Together these findings indicate that GRg1 protects against hepatic insulin resistance via preserving insulin signaling sensitivity and is a promising alternative medicine.

Preliminary Study on the Preventive Effect of Ginsenoside Rg1 on Posttraumatic Stress Disorder in Mice

Objective To study the preventive effect of ginsenoside Rg1 on posttraumatic stress disorder (PTSD) in mice. Methods Single prolonged stress (SPS) animal model was adopted. Mice treated with normal saline, ginsenoside (Rg1) and sertraline after stress were divided into negative control group(SPS+NS), experimental group(SPS+Rg1) and positive control group(SPS+Sertraline) respectively, and a blank control group(NS) was set. On the 8th and 10th days after modeling, the viaduct cross maze experiment and the forced swimming experiment were respectively carried out. Results In the elevated plus maze experiment, the percentage of opening times of mice in the experimental group and the negative control group [(21.11±7.21) %, (20.80±9.06) %] was significantly lower than that in the blank control group and the positive control group [(44.99±7.69) %, (39.35±14.14) %,P < 0.0001].In the forced swimming experiment, the immobility time of mice in the experimental group and the negative control group [(64.05±24.27) s, (51.23±19.76) s] was significantly higher than that in the blank control group and the positive control group [(16.85±6.90) s, (33.26±20.30) s, P < 0.001]. Conclusion The normal dose of ginsenoside Rg1 could not alleviate the anxiety and fear responses in the mice with post-traumatic stress disorder.

Investigations on the effects of ginsenoside-Rg1 on glucose uptake and metabolism in insulin resistant HepG2 cells

Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes. The liver is an important organ responsible for the development of insulin resistance, and exploring liver glucose metabolism is important to study insulin resistance. We first established the model of insulin resistance in HepG2 cells and then treated them with different concentrations of ginsenoside-Rg1. The results showed that ginsenoside-Rg1 is not toxic to HepG2 cells. In addition, ginsenoside-Rg1 relieved the insulin-induced insulin resistance in HepG2 cells. Furthermore, ginsenoside-Rg1 increased the uptake of glucose by reducing reactive oxygen species and down-regulating the phosphorylation level of p38 MAPK. In addition, ginsenoside-Rg1 also decreased the output of glucose by increasing Akt phosphorylation and reducing GSK3β expression. In conclusion, ginsenoside-Rg1 can alleviate the insulin resistance through increasing the uptake of glucose and decreasing the output of glucose.

Effect of ginsenoside Rg1 on activity of spinal microglia and expression of p38 mitogen-activated protein kinase/nuclear transcription factor-kappa B in neuropathic pain rats

Objective To evaluate the effect of analgesia of ginsenoside Rg1(Rg1) in neuropathic pain(NP) and to investigate the changes in activation of both microglial cells in dorsal horn of spinal cord and p38 mitogen-activated protein kinase(p38MAPK)/NF-κB signaling pathway within microglia. Methods Thirty six rats having been intrathecally catheterized successfully were stochastically divided into 6 groups (6 rats for each group) respectively including sham+natural saline group(group A), chronic constrictive injury(CCI)+natural saline group (group B), CCI+low-dose Rg1 group (group C), CCI+middle-dose Rg1 group(group D), CCI+high-dose Rg1 group(group E) and CCI+minocycline group(group F). Among all groups except group A, the left common sciatic nerve of anesthetized rats was exposed to four silk ligatures(3-0) which were tied loosely proximal to the sciatic nerve's trifurcation. Different medicines were injected intrathecally(i.t.) 1 d before and 1 d, 3 d and 5 d after CCI. Behavioral assessment of anti-nociceptive effects was conducted by thermal withdrawal latency(TWL) method. The content of p38MAPK, phosphorylated p65(p-p65)(member of NF-κB superfamily) and ionized calcium binding adaptor molecule-1(IBA-1) was detected by Western blot method. The level of OX-42, one marker of microglia was examined by immunohistochemistry method. Results ① TWL values of group C, group D and group E were significantly higher than value of group B. The effect was in a dose-dependent manner(P<0.05). ② Compared with group B, over-activation of microglia in group C, group D and group E were markedly suppressed, indicated by deeply inhibited expression of IBA-1 and OX-42, two markers of microglia(P<0.05). ③ Phosphorylation of relevant molecules in p38MAPK signaling pathway in comparison to which in group B such as p38MAPK and NF-κB was attenuated abundantly in group C, group D and group E(P<0.05). Conclusions Activation of p38 MAPK/NF-κB signaling pathway in dorsal horn microglia may be a crucial event in the pathogenesis of NP. It is also suggested that Rg1, a new inhibitor of microglia might be a viable therapeutic strategy for treating NP. Key words: Neuropathic pain; Ginsenoside Rg1; Chronic constrictive injury; p38 mitogen-activated protein kinase/nuclear transcription factor-kappa B

Ginsenoside Rg1 improves ischemic brain injury by balancing mitochondrial biogenesis and mitophagy

Purpose: To study the effects of ginsenoside Rg1 on mitochondrial dysfunction induced by ischemic stroke.Methods: Human neuroblastoma SK-N-SH cells, subjected to oxygen-glucose deprivation (OGD), were divided into six groups: control group, OGD group, 3 OGD + Rg1 groups (6.25, 12.5 and 25 μM), and Rg1 (25 μM) group. Apoptosis rate, intracellular production of reactive oxygen species (ROS), and mitochondrial transmembrane potential (MTP) in the OGD cells treated with different concentrations of Rg1 were determined. The mRNA and protein expression levels of mitochondrial biogenesis-related transcription factors and autophagy-related proteins were determined by reat time-polymerase chain reaction (RT-PCR) and Western blotting.Results: ROS production was significantly increased in OGD SK-N-SH cells (p &lt; 0.01), but this was reversed by Rg1 treatment (p &lt; 0.05). Rg1-treated cells had significantly higher MTP when compared with OGD cells (p &lt; 0.01). Rg1 treatment led to significant increases in mRNA and protein expression levels of PGC1-α, NRF-1, and TFAM-1 (p &lt; 0.01). Moreover, Rg1 treatment inhibited apoptosis in SKN- SH cells, and up-regulated autophagy-related proteins in t neuronal injury model. Treatment with autophagy inhibitors decreased the mitochondrial protective effects exerted by Rg1 in OGD SK-N-SH cells.Conclusion: Rg1 improves mitochondrial dysfunction by regulating autophagy in mitochondria. Thus, it may offer protection from brain injuries caused by cerebral ischemia. Keywords: Cerebral ischemia, Ginsenoside Rg1, Mitochondrial dysfunction, Mitophagy