Ginsenoside Rg3 protects heart against isoproterenol-induced myocardial infarction by activating AMPK mediated autophagy.

BACKGROUND: Panax ginseng is a well-known medicinal herb that is widely used in traditional Chinese medicine for treating various diseases. Ginsenoside Rg3 (Rg3) is thought to be one of the most important active ingredients of Panax ginseng. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. METHODS: In the mouse heart injury model induced by isoproterenol (ISO), we used brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and caspase-3 ELISA kits to test myocardium injury. To test whether Rg3 protects myocardial injury through AMPK mediated autophagy, we used specific AMPK inhibitor in combination with Rg3. NLRP3 inflammasome related molecules such as NLRP3, ASC and caspase-1 were measured by western-blot following Rg3 treatment. RESULTS: We found that Rg3 significantly reduced ISO induced myocardial injury indicated by the downregulation of serum BNP and LDH. In addition, we showed that the improvement of myocardial injury by Rg3 was associated with enhanced expression of autophagy related protein and activation of AMPK downstream signaling pathway. CONCLUSIONS: We observed that inhibition of AMPK significantly reversed the myocardial protective effect of Rg3, which is associated with a decrease of Rg3 induced autophagy. These together suggested that Rg3 may improve myocardial injury during MI through AMPK mediated autophagy. Our study also provides important translational evidence for using Rg3 in treating myocardial infarction (MI).

VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis.

VSL#3 probiotics can be effective on induction and maintenance of the remission of clinical ulcerative colitis. However, the mechanisms are not fully understood. The aim of this study was to examine the effects of VSL#3 probiotics on dextran sulfate sodium (DSS)-induced colitis in rats. Acute colitis was induced by administration of DSS 3.5 % for 7 days in rats. Rats in two groups were treated with either 15 mg VSL#3 or placebo via gastric tube once daily after induction of colitis; rats in other two groups were treated with either the wortmannin (1 mg/kg) via intraperitoneal injection or the wortmannin + VSL#3 after induction of colitis. Anti-inflammatory activity was assessed by myeloperoxidase (MPO) activity. Expression of inflammatory related mediators (iNOS, COX-2, NF-κB, Akt, and p-Akt) and cytokines (TNF-α, IL-6, and IL-10) in colonic tissue were assessed. TNF-α, IL-6, and IL-10 serum levels were also measured. Our results demonstrated that VSL#3 and wortmannin have anti-inflammatory properties by the reduced disease activity index and MPO activity. In addition, administration of VSL#3 and wortmannin for 7 days resulted in a decrease of iNOS, COX-2, NF-κB, TNF-α, IL-6, and p-Akt and an increase of IL-10 expression in colonic tissue. At the same time, administration of VSL#3 and wortmannin resulted in a decrease of TNF-α and IL-6 and an increase of IL-10 serum levels. VSL#3 probiotics therapy exerts the anti-inflammatory activity in rat model of DSS-induced colitis by inhibiting PI3K/Akt and NF-κB pathway.

The protective effect of picroside II against hypoxia/reoxygenation injury in neonatal rat cardiomyocytes.

CONTEXT: Picroside II, an iridoid glucoside found in the root of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to possess potent antioxidant activity. However, whether picroside II has a protective effect against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury is poorly understood. OBJECTIVE: To explore the cardioprotective role of picroside II against oxidative stress induced by H/R injury in neonatal rat cardiacmyocytes. MATERIALS AND METHODS: The viability and cellular damage of cardiomyocytes were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the levels of reduced (GSH) and oxidized glutathione (GSSG), and the contents of malondialdehyde (MDA) were determined by a colorimetric method. The levels of intracellular reactive oxygen species (ROS) and calcium were evaluated by flow cytometric analysis. RESULTS: We analyzed the effective half-maximal concentration for protection from the dose-response curves and obtained the concentration of 50 µg/mL as EC(50). Pretreated cardiomyocytes with picroside II (50-200 µg/mL), prior to H/R exposure, inhibited LDH activity in culture media and increased cell viability in a dose-dependent manner. This protective effect was accompanied by significantly increasing reduced GSH contents and the activities of SOD and GSH-Px and attenuating MDA and GSSG contents in response to H/R injury. Furthermore, treatment with picroside II also inhibited ROS production and calcium accumulation in cardiomyocytes. DISCUSSION AND CONCLUSION: The present study demonstrates that picroside II protects cardiomyocytes against oxidative-stress injury induced by H/R through reduction of ROS production and calcium accumulation and enhancement of the activity of antioxidant defense.

Picroside II protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by activating the PI3K/Akt and CREB pathways.

Picroside II, an iridoid glucoside found in the root of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to reduce apoptosis in neuronal cells and other cell types. However, whether picroside II has a protective effect against cardiomyocyte apoptosis is poorly understood. In the present study, we investigated the cardioprotective role of picroside II and the underlying mechanisms in hypoxia/reoxygenation-induced cardiomyocyte apoptosis. The pretreatment with picroside II markedly attenuated hypoxia/reoxygenation-induced cell damage dose-dependently, which was evident by the increased cell viability and the corresponding decrease in lactate dehydrogenase release (LDH). The pretreatment with picroside II inhibited apoptosis confirmed by Annexin V-FITC staining, Hoechst 33258 nuclear staining and by assessment of caspase-3 activity. In addition, we found that picroside II not only increased the expression of Bcl-2, while decreasing Bax expression, but also augmented Akt and cAMP response element-binding protein (CREB) phosphorylation and ultimately inhibited hypoxia/reoxygenation-induced apoptosis. Furthermore, the protective effects of picroside II were abrogated by pretreatment of the cells with wortmannin or LY294002, a specific PI3K inhibitor. The present study suggests that picroside II inhibits hypoxia/reoxygenation-induced apoptosis in cardiomyocytes by activating the PI3K/Akt and CREB pathways and modulating expression of Bcl-2 and Bax.