Protective Effects Of Ginsenoside Rb1 Research Articles

Protective effect of ginsenoside Rb1 against aconitine cardiotoxicity studied by myocardial injury, action potential, and calcium signaling

Aconitine is the main active component of Aconitum plants. Although aconitine has effects that include strengthening the heart, analgesia, anti-tumor, and immune-regulating effects, aconitine has both efficacy and toxicity, especially cardiotoxicity. Severe effects can include arrhythmia and cardiac arrest, which limits the clinical application of aconitine-containing traditional Chinese medicine. Ginsenoside Rb1(Rb1) is mainly found in plants, such as ginseng and Panax notoginseng, and has cardiovascular-protective and anti-arrhythmia effects.This study aimed to investigate the detoxifying effects of Rb1 on aconitine cardiotoxicity and the electrophysiological effect of Rb1 on aconitine-induced arrhythmia in rats.Pathological analysis, myocardial enzymatic indexes, and Western blotting were used to investigate the ameliorating effect of Rb1 on aconitine cardiotoxicity. Optical mapping was used to evaluate the effect of Rb1 on action potential and calcium signaling after aconitine-induced arrhythmia.Rb1 inhibited pathological damage caused by aconitine, decreased myocardial enzyme levels, and restored the balance of apoptotic protein expression by reducing the expression of Bax and cleaved caspase 3 and increasing the expression of Bcl-2, thereby reducing myocardial damage caused by aconitine. Rb1 also reduced the increase in heart rate caused by aconitine, accelerated action potential conduction and calcium signaling, and reduced the dispersion of action potential and calcium signal conduction.Rb1 reduced the cardiotoxicity of aconitine by attenuating aconitine-induced myocardial injury and inhibiting the aconitine-induced retardation of ventricular action potential and calcium signaling in rats.

A novel approach combining network pharmacology and experimental validation to study the protective effect of ginsenoside Rb1 against cantharidin-induced hepatotoxicity in mice.

Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targetswere the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD.

GPCR-Gs mediates the protective effects of ginsenoside Rb1 against oxygen-glucose deprivation/re-oxygenation-induced astrocyte injury

ObjectivesTo investigate whether the protective actions of ginsenoside Rb1 (Rb1) on astrocytes are mediated through the Gs-type G-protein-coupled receptor (GPCR-Gs). MethodsPrimary 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-Gs-specific inhibitors and molecular docking were used to identify target receptors. ResultsRb1 at concentrations ranging from 0.8 to 5 μM 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-Gs inhibitor NF449 was introduced, the protective effects of Rb1 completely disappeared, and its activation of cAMP and Akt signaling pathways was significantly inhibited. ConclusionRb1 protects against astrocytes from OGD/R-induced injury through GPCR-Gs mediation.

Regulation of NAD+/NADH Redox Involves the Protective Effects of Ginsenoside Rb1 against Oxygen-Glucose Deprivation/Reoxygenation-Induced Astrocyte Lesions.

The aim of this study was to investigate NAD+/NADH redox regulation in astrocytes by Ginsenoside Rb1 subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and to reveal the neuroprotective mechanism of ginseng. Neonatal mouse brain was used to culture primary astrocytes. The third generation of the primary astrocytes was used for the experiments. OGD/R was introduced by culturing the cells in a glucose-free media under nitrogen for 6 h followed by a regular culture for 24 h. Ginsenoside Rb1 attenuated OGD/R-induced astrocyte injury in a dose-dependent manner. It improved the mitochondrial function of OGD/R astrocytes indicated by improving mitochondrial distribution, increasing mitochondrial membrane potential, and enhancing mitochondrial DNA copies and ATP production. Ginsenoside Rb1 significantly lifted intracellular NAD+/NADH, NADPH/NADP+, and GSH/GSSG in OGD/R astrocytes. It inhibited the protein expression of both PARP1 and CD38, while attenuating the SIRT1 drop in OGD/R cells. In line with its effects on PARP1, Ginsenoside Rb1 significantly reduced the expression of poly-ADP-ribosylation (PARylation) proteins in OGD/R cells. Ginsenoside Rb1 also significantly increased the expression of NAMPT and NMNAT2, both of which are key players in NAD/NADH synthesis. The results suggest that the regulation of NAD+/NADH redox involves the protective effects of ginsenoside Rb1 against OGD/R-induced astrocyte injury.

Ginsenoside Rb1 alleviates chronic intermittent hypoxia-induced diabetic cardiomyopathy in db/db mice by regulating the adenosine monophosphate-activated protein kinase/Nrf2/heme oxygenase-1 signaling pathway.

To examine the protective effect of ginsenoside Rb1 (Rb1), the main component of Renshen (), on cardiomyopathy in db/db mice exposed to chronic intermittent hypoxia (CIH) and explore the potential underlying mechanism of Rb1 in treating diabetic cardiomyopathy (DCM). The db/db mice were randomly separated into five groups: normal control group, model group, Rb1 20 mg/kg group, Rb1 40 mg/kg group, and glucagon-like peptide-1 (GLP-1) group. Mice were exposed to air-condition or CIH for 8 weeks, and Rb1 and GLP-1 were administrated before CIH exposure every day. Oral glucose tolerance test (OGTT), intraperitoneal insulin tolerance test (IPITT), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were detected to evaluate glycolipid metabolism. The level of insulin was detected by a mouse enzyme-linked immunosorbent assay (ELISA). Cardiac function was detected by echocardiography, and myocardial pathology was observed by hematoxylin-eosin and Masson staining. The expression of collagen Ⅰ and collagen Ⅲ was detected by immunohistochemistry. Adenosine monophosphate-activated protein kinase (AMPK)/Nrf2/heme oxygenase-1 (HO-1) signaling pathway was detected by Western blot and immunofluorescence. Rb1 treatment could improve glucose tolerance and the level of cardiac function indexes, and inhibit the level of oxidative stress indexes and the expression of collagen Ⅰ and collagen Ⅲ. Moreover, Rb1 treatment enhanced AMPK phosphorylation and increased Nrf2 and HO-1 expression. Rb1 treatment alleviated CIH-induced diabetic cardiomyopathy and glycolipid metabolism disorders in db/db mice by inhibiting oxidative stress and regulating the AMPK/Nrf2/HO-1 signaling pathway.

Involvement of Autophagy in the Protective Effects of Ginsenoside Rb1 in a Rat Model of Traumatic Brain Injury.

No treatment modalities have been identified to prevent neuron damage induced by traumatic brain injury (TBI). The objective of this study was to investigatewhether ginsenoside Rb1 (GS-Rb1) could be utilized to exert neuroprotective effects in TBI. Lateral fluid percussion injury (LFPI) was used to induce an experimental TBI model. Lewis rats were divided into a GS-Rb1 group (5, 10, 20mg/kg, intraperitoneally injected daily), a sham group, and a vehicle group. Neurological impairments were assessed with brain water content, Evans blue extravasation, neurological deficit scores, and Morris water maze test. TUNEL and NeuN staining were utilized to detect neuron apoptosis. The relative expression of apoptosis- and autophagy-relevant molecules were assayed with real-time PCR and western blot. GS-Rb1 inhibited TBI-induced brain edema and Evans blue extravasation in a dose-dependent manner. Furthermore, GS-Rb1 improved neurological impairments with diminished neurological deficit scores, decreased escape latencies, increased time in the target quadrant, and increased number of platform site crossings. GS-Rb1 protected against neuron apoptosis with downregulated Bax expression and upregulated Bcl-2 expression. It was worth noting that TBI increased the LC3II/LC3I ratio and upregulated the relative expression of Beclin-1, Atg-7, and Atg-3; moreover, TBI downregulated the relative expression of P62. The administration of GS-Rb1 further strengthened the relative expression of autophagy-related molecules. GS-Rb1 alleviates neurological impairments induced by TBI with upregulated autophagy.

Ginsenoside-Rb1 prevents bone cartilage destruction through down-regulation of p-Akt, p-P38, and p-P65 signaling in rabbit

BackgroundOsteoarthritis (OA) is the most common joint complaint resulting in pain, disability, and loss of quality of life. On the other hand, ginsenoside-Rb1 is a plant product derived from ginseng that possesses immune-regulation and anti-inflammatory activities. However, it has been reported that different rout of administration but hydrogel-based Ginsenoside-Rb1 in an OA rabbit model has not been investigated. PurposeThe aim of this study was to investigate the potential effects of ginsenoside-Rb1 such as anti-arthritic activity in a rabbit knee OA model via NF- κB, PI3K/Akt, and P38/(MAPK) pathways. Study DesignIn the current study, rabbit osteoarthritis was induced by hollow trephine on the femur trochlea and the hydrogel-based Ginsenoside-Rb1 sheets were inserted on the rabbit knee to assess the anti-arthritis activity of ginsenoside-Rb1 which is sustained release. MethodsAfter the hydrogel-based Rb1 sheet insert on the rabbit knee, macroscopic and micro CT was performed for investigation of chondroprotective effect. Matrix metalloproteinases (MMPs) and apoptotic expression were assessed through Immunohistochemistry and RT-PCR assay. In addition, the flow cytometry technique was used for the investigation of intracellular reactive oxygen species (ROS) production and histological changes were examined by HE, safranin O, and Masson trichrome staining method. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were investigated using Western blot analysis. ResultsMacroscopic and micro CT investigation of hydrogel-Rb1 treatment showed a dose-dependent chondroprotective effect. Immunohistochemistry and RT-PCR revealed that expression of matrix metalloproteinases (MMPs) and apoptotic markers TNF-α, caspase-3, and bax are down-regulated in a dose-dependent fashion following implantation of hydrogel-Rb. Higher levels of intracellular reactive oxygen species (ROS) were observed in the OA group. In histopathological investigation of hydrogel-Rb1 exhibited larger amounts of chondro cells, glycosaminoglycan's, and collagen compared to the defect group. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were downregulated by hydrogel-Rb1 while the disease model showed upstream. In the meantime, MMP expression level was considerably down-regulated. ConclusionsOur results indicate the protective effect of ginsenoside-Rb1 against OA pathogenesis through prevention of apoptosis with suppression of ROS production and activation of NF-κB signaling through downregulation of the MAPK and PI3K/Akt signaling pathways.

Protective Effects of Ginsenoside Rb1 in Rats with Diabetic Cardiomyopathy

Ginsenosides play an important role in the treatment of diabetes and obesity. Our group predicted that ginsenoside Rb1 combined with insulin would have a protective effect in diabetic cardiomyopathy. Diabetic model was established by high fat feeding combined with intraperitoneal injection of 70 mg/ kg streptozotocin in 8 w old male Sprague-Dawley rats. One rat was sacrificed at 8 w, 12 w and 14 w, respectively. The cardiac function and pathological structure of the myocardium were observed. It was concluded that the model of the diabetic cardiomyopathy group was successful. Rats were randomly divided into 4 groups and treated with different doses for 6 w. During this period, all rats received regular blood from the tail vein, had regular random blood glucose measurements and had regular fasting body weight measurements. After 6 w of intervention, cardiac ultrasonography was performed to evaluate cardiac function in all groups. Blood samples of aorta were collected for biochemical detection and pathological staining, immunohistochemical staining, reverse transcription polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay were taken from heart tissue samples for detection. Compared with the normal group, diabetic cardiomyopathy rats displayed severe hyperglycemia, lower body weight, poorer cardiac performance, cardiac fibrosis and cardiac inflammation. Diabetic cardiomyopathy rats suffered obvious effects from over-activation of the heparin-binding epidermal growth factor pathway. Ginsenoside Rb1 treatment attenuated hyperglycemia, body weight loss and cardiac injury as well as heparin-binding epidermal growth factor activation induced by diabetic cardiomyopathy. Meanwhile, ginsenoside Rb1 had no obvious toxicity or side effects in the heart, liver or kidneys. Ginsenoside Rb1 treatment in diabetic rats can inhibit the over-activated heparin-binding epidermal growth factor signaling pathway, attenuate fibrosis of myocardial tissue and improve cardiac function, and has no obvious toxicity or side effects. It is a potential drug for diabetic heart disease.

Protective effect of ginsenoside Rb1 against chronic restraint stress (CRS)-induced memory impairments in rats

Ginsenoside Rb1 (Rb1) is one of the most active components found in ginseng and provides important benefits to the central nervous system, especially for the improvement of learning and memory. Previous studies demonstrated that Rb1 protected against scopolamine-induced amnesia and exhibited memory-enhancing effects in the SAMP8 mouse model. However, the effects of Rb1 against chronic restraint stress (CRS)-induced cognitive impairments, especially the role of Rg1 on the performance of reward directed instrumental conditioning have not been investigated. In this study, rats were subjected to CRS (6 h/day) for 28 days. Thereafter, behavioural tests including reward-directed instrumental conditioning task (RICT) and the Morris water maze (MWM) task were conducted. Administered of Rb1 (6.75 and 13.5 mg/kg, i.p.) remarkably ameliorated the memory impairments caused by CRS as evident from the results of RICT and MWM task, and this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) in the hippocampus. Additionally, Rb1 reduced the ratio of Bax:Bcl-2 and the expression of cleaved caspase-3 and cleaved caspase-9, increased the levels of synaptophysin (SYP) and postsynaptic density 95 (PSD95) and activated the BDNF/TrkB pathway in the hippocampus. In summary, the present study demonstrated that Rb1 rescues cognitive deficits induced by CRS is partially mediated by antagonizing oxidative stress and apoptosis, improving synaptic plasticity and restoring the BDNF/TrkB signalling pathway. This newly discovered effect of Rb1 sheds light on its applications in the development of therapeutic interventions to alleviate the deleterious effects of chronic stress.

Ginsenoside Rb1 Inhibits Cardiomyocyte Autophagy via PI3K/Akt/mTOR Signaling Pathway and Reduces Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion injury (MIRI) is the major cause of myocardial cell damage in acute myocardial infarction, and its treatment remains a clinical challenge. Ginsenoside Rb1 showed protective effects on the cardiovascular system; however, the underlying mechanism remains largely unclear. Effects of Ginsenoside Rb1 on rat MIRI-induced myocardial infarct size were evaluated through TTC staining. TUNEL assay and flow cytometry analysis were employed to estimate cell apoptosis. Apoptosis, autophagy and PI3K/Akt/mTOR pathway-related proteins were estimated via western blot. Expression of Beclin1 in myocardial tissues were examined by immunohistochemical analysis. Expression levels of IL-1[Formula: see text], TNF-[Formula: see text] and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA). Here, we found that Ginsenoside Rb1 treatment not only alleviated MIRI in rats but also protected H9C2 cells against hypoxia/reoxygenation induced damage. Ginsenoside Rb1 abolished the MIRI-induced activation of autophagy. Meanwhile, we found that treatment of 3-MA (autophagy inhibitor) could enhance the protective effects of Ginsenoside Rb1 on H9C2 cells during H/R. Moreover, Ginsenoside Rb1 treatment resulted in the activation of the PI3K/Akt/mTOR pathway, and treatment of LY294002 (PI3K/Akt pathway repressor) abolished the protective effects of Ginsenoside Rb1 on myocardial in vitro and in vivo. Our results suggest that Ginsenoside Rb1 functions as a protector against MIRI by repressing cardiomyocyte autophagy through the PI3K/Akt/mTOR signaling pathway.

RETRACTION NOTICE: Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210.

RETRACTION NOTICE: Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210.

Expression Of Concern: 'Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210'.

Expression Of Concern: 'Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210'.

Protective effects of ginsenoside Rb1 in rats with diabetic cardiomyopathy

Protective effects of ginsenoside Rb1 in rats with diabetic cardiomyopathy

Ginsenoside Rb1 ameliorates autophagy via the AMPK/mTOR pathway in renal tubular epithelial cells in vitro and in vivo

Although ginsenoside Rb1 (G-Rb1) has exerted an inhibitory effect on renal fibrosis and progression of chronic kidney disease (CKD), its mechanism remains unknown. This study aims to explore the anti-fibrosis effect of G-Rb1 in unilateral ureter obstruction (UUO) mouse model and underlying mechanisms in HBSS-induced HK-2 cells. In vivo, renal function, kidney histological pathology, and autophagy-related protein molecules were assessed. Additionally, rapamycin, Deptor overexpression plasmid, Akt inhibitor, metformin, and a p38-MAPK inhibitor, as well as an ERK-MAPK inhibitor were used to evaluate the effect of AMPK/mTOR, Akt and MAPK signal pathways on the protective effect of G-Rb1 in HK-2 cells. Treatment with G-Rb1 significantly improved renal dysfunction. G-Rb1 reversed UUO-induced downregulation of p62, and upregulation of LC3 and the ratio of LC3 I/II, indicating that G-Rb1 restrained UUO-induced activation of autophagy. Furthermore, we found that treatment of HBSS-induced HK-2 cells with G-Rb1 resulted in AMPK/mTOR and ERK, p38 MAPKs signaling pathways regulated autophagy inhibition. These findings may explain, in part, the molecular mechanisms by which G-Rb1 could be applied in the treatment of patients with CKD, further suggesting that autophagy and its associated molecular signaling pathway may be new targets for the treatment of renal fibrosis and CKD.

Ginsenoside Rb1 pretreatment attenuates myocardial ischemia by reducing calcium/calmodulin-dependent protein kinase II-medicated calcium release

Objective: The aim of this study was to investigate the protective effects of ginsenoside Rb1 and assess whether these protective effects are related to calcium/calmodulin-dependent protein kinase II (CaMKII).Methods: A myocardial ischemia (IS) rat. model and a myocardial H9C2 cell hypoxia model were established. MI was induced by occluding the left anterior descending artery for 120 min. Ginsenoside Rb1 (10 mg/kg) was administered 30 min before ischemia induction, and the treatment continued for 7 days. Results: In the rat IS injury model, ginsenoside Rb1 reduced myocardial infarct size, mean left ventricular diastolic pressure, incidence of arrhythmia, and levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde. However, the mean left ventricular systolic pressure, and maximal rising and falling rates of ventricular pressure (±dp/dtmax) increased. In the myocardial H9C2 cell hypoxia model, ginsenoside Rb1 reduced intracellular calcium concentrations ([Ca2+ ]i) during hypoxia, and markedly reversed the hypoxia-induced decrease in cell survival. Ginsenoside Rb1 was involved in the downregulation of CaMKII and the ryanodine receptor, as well as hypoxia-induced H9C2 cell survival. Conclusion: The findings of the present study suggest that ginsenoside Rb1 attenuates MI injury in rats, partially through the downregulation of CaMKII expression.

Particulate Matter 2.5 Mediates Cutaneous Cellular Injury by Inducing Mitochondria-Associated Endoplasmic Reticulum Stress: Protective Effects of Ginsenoside Rb1.

The prevalence of fine particulate matter-induced harm to the human body is increasing daily. The aim of this study was to elucidate the mechanism by which particulate matter 2.5 (PM2.5) induces damage in human HaCaT keratinocytes and normal human dermal fibroblasts, and to evaluate the preventive capacity of the ginsenoside Rb1. PM2.5 induced oxidative stress by increasing the production of reactive oxygen species, leading to DNA damage, lipid peroxidation, and protein carbonylation; this effect was inhibited by ginsenoside Rb1. Through gene silencing of endoplasmic reticulum (ER) stress-related genes such as PERK, IRE1, ATF, and CHOP, and through the use of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), it was demonstrated that PM2.5-induced ER stress also causes apoptosis and ultimately leads to cell death; however, this phenomenon was reversed by ginsenoside Rb1. We also found that TUDCA partially restored the production of ATP that was inhibited by PM2.5, and its recovery ability was significantly higher than that of ginsenoside Rb1, indicating that the process of ER stress leading to cell damage may also occur via the mitochondrial pathway. We concluded that ER stress acts alone or via the mitochondrial pathway in the induction of cell damage by PM2.5, and that ginsenoside Rb1 blocks this process. Ginsenoside Rb1 shows potential for use in skin care products to protect the skin against damage by fine particles.

GinsenosideRb1 prevents steroid‑induced avascular necrosis of the femoral head through the bone morphogeneticprotein‑2 and vascular endothelial growth factor pathway.

At present, the molecular mechanism underlying the protective effect of Ginsenoside Rb1 remains unclear. The present study was designed to investigate whether Ginsenoside Rb1 weakened the steroid-induced avascular necrosis of the femoral head (SANFH) and to explore the possible mechanisms of the above effects. As a result, it was revealed that Ginsenoside Rb1 was protective against steroid-induced avascular necrosis and inhibited serum osteocalcin in a rat model of SANFH. Ginsenoside Rb1 reduced inflammation, oxidative stress and bone cell apoptosis in a rat model of SANFH. Furthermore, Ginsenoside Rb1 attenuated trabecula parameters, total cholesterol and low density lipoprotein/high density lipoprotein in SANFH rat. Additionally, Ginsenoside Rb1 significantly reversed alkaline phosphatase and osteocalcin activities, vascular endothelial growth factor (VEGF) receptor, VEGF, Runt related transcription factor 2 (Runx2) and bone morphogenetic protein (BMP)-2 protein expression in SANFH rat. Collectively, the present study demonstrated that Ginsenoside Rb1 attenuated SANFH through the VEGF/RUNX2/BMP-2 signaling pathway.

Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway.

Ginsenoside Rb1 (GRb1), one of the major active saponins isolated from ginseng, has recently been reported to protect various organs against ischemia/reperfusion (IR) injury; however, the mechanisms underlying these protective effects following intestinal IR (IIR) remain unclear. The present study aimed to evaluate the effects of GRb1 on IIR injury and determine the mechanisms involved in these effects. Sprague Dawley rats were subjected to 75 min of superior mesenteric artery occlusion, followed by 3 h of reperfusion. GRb1 (15 mg/kg) was administered intraperitoneally 1 h prior to the induction of IIR, with or without intravenous administration of Wortmannin [WM; a phosphoinositide 3-kinase (PI3K) inhibitor, 0.6 mg/kg]. The degree of intestinal injury and oxidative stress-induced damage was determined by histopathologic evaluation and measurement of the serum activity levels of D-lactate, diamine oxidase and endotoxin, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and 8-iso-prostaglandin F2α (8-iso-PGF2α). The protein expression levels of p85, phosphorylated (p)-p85, protein kinase B (Akt), p-Akt and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined via western blotting, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were measured via ELISA. It was revealed that IIR led to severe intestinal injury (as determined by significant increases in intestinal Chiu scores), which was accompanied with disruptions in the integrity of the intestinal mucosal barrier. IIR also increased the expression levels of TNF-α, IL-1β, IL-6, MDA and 8-iso-PGF2α in the intestine, and decreased those of SOD. GRb1 reduced intestinal histological injury, and suppressed inflammatory responses and oxidative stress. Additionally, the protective effects of GRb1 were eliminated by WM. These findings indicated that GRb1 may ameliorate IIR injury by activating the PI3K/protein kinase B/Nrf2 pathway.

Ginsenoside Rb1 protects cardiomyocytes from oxygen-glucose deprivation injuries by targeting microRNA-21.

Ginsenoside Rb1 (GS-Rb1) is one of the most important active pharmacological extracts of the traditional Chinese medicine, ginseng, and there is extensive evidence of its cardioprotective properties. However, the microRNA (miR) targets of GS-Rb1 and the underlying mechanisms of GS-Rb1 and miR-21 in the progression of cardiomyocyte apoptosis have not been clearly elucidated. The aim of the current study was to investigate the impact of miR-21 and its target gene, programmed cell death protein 4 (PDCD4), on the protective effect of GS-Rb1 in cardiomyocytes injured by oxygen-glucose deprivation (OGD). The miR-21 expression levels were downregulated, and the percentage of the apoptotic cells and reactive oxygen species (ROS) was increased in OGD-cultured neonatal rat cardiomyocytes; however, the effects were reversed by GS-Rb1 treatment. It was demonstrated that GS-Rb1 could reduce intracellular ROS content, and the expression of cytochrome C and the pro-apoptosis protein, apoptosis regulator B-cell lymphoma associated X (Bax) protein while increasing the expression of the anti-apoptosis protein, apoptosis regulator Bcl-2. The target gene, PDCD4, was significantly upregulated in the OGD group; however, the expression of PDCD4 was inhibited by GS-Rb1 treatment. Furthermore, miR-21 inhibitor transfection reduced GS-Rb1-induced miR-21 upregulation compared with the OGD+GS-Rb1 group, indicating that the miR-21 was involved in the anti-apoptotic effect of GS-Rb1 in cardiomyocytes. The results of the current study highlighted that GS-Rb1 could target miR-21 and its target gene, PDCD4, to protect OGD-injured cardiomyocytes. The results of the current study may provide a novel insight for the treatment of myocardial infarction with Traditional Chinese Medicines, involving miRs as targets.

Protective effects of ginsenoside Rb1 on H2O2-induced oxidative injury in human endothelial cell line (EA.hy926) via miR-210.

Ginsenoside Rb1 (Rb1) possesses a cardioprotective effect via mediating microRNAs (miRs), while it is unexplored whether miR-210 is regulated by Rb1 in response to oxidative stress. Human endothelial EA.hy926 cells were stimulated with H2O2 before Rb1 treatment. After transfection, cell viability, apoptosis, migration, and invasion assays were conducted. Western blot was applied to quantify protein. BCL2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) and miR-210 were analyzed with quantitative reverse transcription polymerase chain reaction. Dual luciferase activity assay was performed. Rb1 elevated viability, migration, and invasion of H2O2-treated cells. H2O2-induced apoptosis was moderated by Rb1. miR-210 was augmented in H2O2-treated cells after Rb1 stimulation. miR-210 inhibitor abolished the positive effects of Rb1. BNIP3 was negatively modulated by miR-210 and implicated in modulating viability, apoptosis, and migration and invasion. In addition, BNIP3 modulated phosphorylation of regulators. Rb1 repressed oxidative injury via elevating miR-210. miR-210 negatively mediated BNIP3, which participated in oxidative damage via regulating mammalian targets of rapamycin (mTOR) and nuclear factor-κB (NF-κB).