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Highlights • Rb3 significantly inhibited CSE-induced inflammatory responses by inhibiting the p38 MAPK/NF-κB pathway in fibroblasts and epithelial cells. • Rb3 pretreatment led to the increase of anti-oxidant activity to reduce oxidative stress injury in CSE-induced fibroblasts and epithelial cells. • Rb3 decreased CSE-induced excessive accumulation of ECM by inhibiting TGF-β1/VEGF pathway in fibroblasts and epithelial cells. Abstract Cigarette smoke causes many adverse effects such as inflammation, oxidative stress, and excessive accumulation of the extracellular matrix (ECM). Ginsenoside Rb3 has anti-inflammatory and anti-oxidative effects, which may contribute to delaying the injury caused by cigarette smoke. In this study, we used cigarette smoke extract (CSE) to establish cell injury models in WI-38 human fetal lung fibroblasts and 16HBE human bronchial epithelial cells. Our results showed that Rb3 protected against CSE-induced cytotoxicity in both cell lines. In addition, it significantly inhibited the secretion of inflammatory factors, such as interleukin-8 and tumor necrosis factor alpha, by inhibiting the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). Moreover, Rb3 pre-treatment led to an increase in the levels of glutathione (GSH) and activities of superoxide dismutase, glutathione peroxidase (GSH-Px), and catalase to reduce the oxidative stress induced by CSE. Additionally, Rb3 decreased the levels of ECM proteins including collagen I (Col I), Col III, and elastin after CSE treatment by inhibiting the expression of transforming growth factor beta 1 (TGF-β1)-induced vascular endothelial growth factor (VEGF). Our findings suggest that Rb3 prevented CSE-induced inflammation and oxidative stress as well as the excessive accumulation of ECM in WI-38 and 16HBE cells to protect against cell injury by inhibiting the p38 MAPK/NF-κB and TGF-β1/VEGF pathways. The results of this study may be valuable for the development of Rb3 to combat the damage caused by cigarette smoke. [ABSTRACT FROM AUTHOR]

A causal relationship between ginsenoside Rb3 (G-Rb3) and improved inflammation and cardiac function has not been established. To determine which specific signaling pathways were involved in G-Rb3 improvement of inflammation and myocardial function. In vivo , we found that G-Rb3 decreased the levels of both nuclear factor κB (NF-κB p65) and CD45, an inflammatory marker. G-Rb3 also enhanced key proteins of the contraction unit (cardiac troponin protein I (cTnI) and α-actinin) to improve cardiac function. G-Rb3 inhibited NF-κB p65 nuclear translocation in vitro, as verified by western blot and IF. When NF-κB p65 was overexpressed, a decrease in cyclic nucleotide phosphodiesterase 3B (PDE3B) and SERCA2a expression, while no statistical significance was observed in the expressions of cAMP, PKA, and calcium/calmodulin-dependent protein kinase type II (CaMKⅡ) in each group. The NF-κB p65 plasmid blocked the SERCA2a promoter, as verified by the luciferase reporter system, and G-Rb3 truncated the NF-κB p65 block on the SERCA2a promoter. qPCR was also used to confirm that G-Rb3 increased the mRNA of SERCA2a. In conclusion, we confirmed that the mechanisms of G-Rb3 on ventricular systolic dysfunction causing inflammation are not via the cAMP/PKA pathway, but via suppressing the blockage of NF-κB p65 on the SERCA2a promoter and increasing the SERCA2a expression. [Display omitted] • NF-κB p65 regulated SERCA2a by directly binding at the SERCA2a promoter rather than the cAMP/PKA pathway. • The molecular mechanism of ginsenoside Rb3 in the relation between the inflammation and contractile activity is implicated in that G-Rb3 truncated the NF-κB p65 blocker on the SERCA2a promoter. [ABSTRACT FROM AUTHOR]

Abstract: Ginsenosides, the most important secondary metabolites in ginseng, have various biological activities. Many studies have focused on the conversion of one of the major ginsenosides, Rb1, to the more active minor ginsenoside, Rg3. This study was carried out to investigate the effect of gamma irradiation on the conversion of Rb1 to Rg3. Rb1 solutions were gamma-irradiated at doses of 10 and 30kGy and analyzed by high performance liquid chromatography (HPLC). HPLC chromatograms showed a decreased content of Rb1 with increasing irradiation dose, but the content of Rg3 was increased. The highest content of Rg3 was present in the 30kGy-irradiated Rb1 sample. The cytotoxic effects tested in cancer cell lines were increased in the gamma-irradiated group. Therefore, these results suggest that gamma irradiation can be an effective method for the conversion of the ginsenoside Rb1 to Rg3. [Copyright &y& Elsevier]

Abstract: The present study was designed to evaluate the effect of ginsenoside Rb3 on myocardial injury and heart function impairment induced by isoproterenol in rats. To induce myocardial ischemia, Sprague–Dawley rats were subcutaneously injected with isoproterenol (20mg/kg). Cardiac marker enzymes and antioxidative parameters in left ventricles were measured. Hemodynamic parameters were monitored and recorded as well. Histopathological examination of left ventricles was performed. It was found that the levels of creatine kinase and lactate dehydrogenase in isoproterenol-treated rats were significantly increased. The rats administrated with isoproterenol showed the declines in left ventricular systolic pressure, positive and negative maximal values of the first derivative of left ventricular pressure, and an elevation of left ventricular end diastolic pressure. Isoproterenol enhanced the content of malondialdehyde and decreased the activities of superoxide dismutase, catalase in left ventricles. Administration of ginsenoside Rb3 significantly ameliorated myocardial injury and heart function impairment induced by isoproterenol. The cardioprotective effect of ginsenoside Rb3 was further confirmed by histopathological examination. Ginsenoside Rb3 also alleviated the increase of malondialdehyde content and decrease of superoxide dismutase and catalase activities in left ventricles. The results indicated that ginsenoside Rb3 possesses the effect against isoproterenol-induced myocardial injury and heart function impairment, and that the mechanism of pharmacological action was related to the antioxidant activity of ginsenoside Rb3 at least in part. [Copyright &y& Elsevier]

Abstract: In this work, the separation of ginsenoside Rb3 and Rc from the crude extracts of caudexes and leaves of Panax notoginseng (CECLPN) was studied with reversed-phase high-performance liquid chromatography (RP-HPLC). The chromatographic separation was achieved using a SynChropak C18 column (at 25°C). A satisfied separation of the compounds was obtained in less than 40min with a flow rate of 1.0ml/min. Chromatography was performed using ternary mobile phase composed of methanol, water and phosphoric acid, 65:33:1.4 (v/v). UV detection was accomplished at 203nm. Ginsenoside Rb3 and Rc found in the CECLPN constitute up to 38.25% and 26.65% of the dry powder, respectively. Ginsenoside Rb3 and Rc were prepared by semi-preparative HPLC/ELSD using gradient elution system of methanol–water=70:30→65:35 at a flow rate of 30ml/min with a sample load of 300–400mg. With this chromatographic condition, each individual ginsenoside Rb3 and Rc in purity of more than 97% were gained. The products were confirmed by spectroscopic (UV, IR, ESI-MS/MS, NMR) and HPLC methods. The methods were validated for linearity, precision, recovery, limits of detection (LOD) and limits of quantification (LOQ). The results show that the proposed method appears to be an adequate method for quality control of CECLPN and a useful tool for pharmaceutical study of ginsenosides. [Copyright &y& Elsevier]

Abstract: Whole-cell patch-clamp technique was used to investigate the effect of ginsenoside Rb3 (Rb3), an active constituent of Panax ginseng, on glycine receptor activity in immature hippocampal neurons, which were dissociated acutely from hippocampal CA1 area in Sprague–Dawley rats aging 10–14 days using the method of enzyme digestion with mechanical dissociation. As a result, glycine elicited an inward current (I gly) in a concentration-dependent manner in approximately 86% of those isolated neurons tested. This current was strychnine-sensitive. Rb3 itself did not elicit any membrane currents. However, coapplication of Rb3 inhibited peak current of I gly. This depressant effect of Rb3 varied with its concentrations. At a concentration of 0.1 μmol/L, ginsenoside Rb3 had the most significant inhibition, with a net reduction of 31% in average. Moreover, the inhibition of I gly by Rb3 did not depend on the membrane potential. Rb3 (0.1 μmol/L) presented inhibitory effect on I gly mainly at higher glycine concentrations (>100 μmol/L), and decreased maximal glycine efficacy. This effect was the same as that of a non-competitive antagonist of glycine receptors. Finally, we found that Rb3 prolonged the time constant of activation of I gly. It is therefore suggested that ginsenoside Rb3, possibly as a non-competitive antagonist, could inhibit strychnine-sensitive glycine current at a dose-dependent manner in acutely dissociated hippocampal CA1 neurons of young rats, and decrease of affinity of glycine to receptors and delay of receptor activation may be involved in this inhibition. Inhibitory effect of ginsenoside Rb3 on I gly is possibly one of the bases of many pharmacological actions of Panax ginseng. [Copyright &y& Elsevier]

Abstract: Aim of the study: To investigate the effect of ginsenoside Rb3 on synaptic transmission after oxygen–glucose deprivation in vitro. Materials and methods: The population spike (PS) was recorded in the stratum pyramidale of mouse hippocampal slices using extracellular recordings. Results: Ginsenoside Rb3 depressed the basal synaptic transmission, which also promoted the recovery amplitude of PS after OGD in a concentration-dependent manner. The GABAA receptor agonist muscimol improved the recovery, which was similar to that of ginsenoside Rb3. Moreover, the effect of ginsenoside Rb3 in combination with muscimol was not additive. Treatment with the GABAA receptor antagonist bicuculline or picrotoxin, which prevented the depression of PS caused by ginsenoside Rb3, also reduced the neuroprotection. Conclusion: The results indicate that the activation of the GABAA receptor is correlated with the neuroprotective mechanisms of ginsenoside Rb3. [Copyright &y& Elsevier]

• Both experiments in vivo and in vitro have verified that G-Rb3 is targeted on PPARα and activate it. • G-Rb3 exerts cardio-protective effect through inhibiting apoptosis and up-regulating energy metabolism. • This study will provide a promising strategy for TCM and contribute to the discovery of alternative therapeutic drugs for HF. Heart failure (HF) leads to an increase in morbidity and mortality globally. Disorders of energy metabolism and apoptosis of cardiomyocytes are critically involved in the progression of HF. Ginsenoside Rb3 (G-Rb3) is a natural product derived from ginseng that has cardio-protective effect. The pharmacological mechanism of G-Rb3 in the treatment of HF remains to be clarified. In this study, we aimed to explore the regulative effects of G-Rb3 on fatty acids oxidation and apoptosis by in vivo and in vitro studies. Myocardial infarction (MI)-induced HF mice model and a cellular H9C2 injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The results showed that G-Rb3 could protect heart functions in MI-induced HF model. G-Rb3 treatment up-regulated expressions of key enzymes involved in β-oxidation of fatty acids, including carnitine palmitoyltransterase-1α (CPT-1α), acyl-CoA dehydrogenase long chain (ACADL) and the major mitochondrial deacetylase enzyme sirtuin 3 (SIRT3). The upstream transcriptional regulator, peroxisome proliferator-activated receptor α (PPARα), was also up-regulated by G-Rb3 treatment. In vitro study demonstrated that G-Rb3 could protect mitochondrial membrane integrity and exert anti-apoptotic effects, in addition to regulating fatty acids oxidation. Impressively, after cells were co-treated with PPARα inhibitor, the regulative effects of G-Rb3 on energy metabolism and apoptosis were abrogated. Our study suggests that G-Rb3 is a promising agent and PPARα is potential target in the management of HF. [ABSTRACT FROM AUTHOR]