Notoginsenoside R1 Protects Against High Glucose-Induced Cell Injury Through AMPK/Nrf2 and Downstream HO-1 Signaling

Notoginsenoside R1 (NGR1), the primary bioactive compound found in Panax notoginseng, is believed to have antihypertrophic and antiapoptotic properties, and has long been used to prevent and treat cardiovascular diseases. However, its potential role in prevention of diabetic cardiomyopathy remains unclear. The present study aimed to investigate the mechanism of NGR1 action in high glucose-induced cell injury. H9c2 cardiomyocytes were cultured in a high-glucose medium as an in-vitro model, and apoptotic cells were visualized using TUNEL staining. Expression of Nrf2 and HO-1 was measured using Western blotting or reverse transcription-quantitative PCR (RT-qPCR). The Nrf2 small interfering (si) RNA was transfected into cardiomyocytes using Opti-MEM containing Lipofectamine® RNAiMAX. NGR1 protected H9c2 cardiomyocytes from cell death, apoptosis and hypertrophy induced by high glucose concentration. Expression of auricular natriuretic peptide and brain natriuretic peptide was remarkably reduced in NGR1-treated H9C2 cells. Western blot analysis showed that high glucose concentration markedly inhibited AMPK, Nrf2 and HO-1, and this could be reversed by NGR1 treatment. However, the cardioprotective effect of NGR1 was attenuated by compound C, which reverses Nrf2 and HO-1 expression levels, suggesting that AMPK upregulates Nrf2 and HO-1 gene expression, protein synthesis and secretion. Transfection of H9C2 cells with Nrf2 siRNA markedly reduced the cardioprotective effect of NGR1 via reduced expression of HO-1. These results indicated that NGR1 attenuated high glucose-induced cell injury via AMPK/Nrf2 signaling and its downstream target, the HO-1 pathway. We conclude that the cardioprotective effects of NGR1 result from upregulation of AMPK/Nrf2 signaling and HO-1 expression in cardiomyocytes. Our findings suggest that NGR1 treatment might provide a novel therapy for diabetic cardiomyopathy.

Caffeine increases performance and leads to a cardioprotective effect during intense exercise in cyclists

The present study was designed to investigate the effects of different caffeine dietary strategies to compare the impact on athletic performance and cardiac autonomic response. The order of the supplementation was randomly assigned: placebo(4-day)-placebo(acute)/PP, placebo(4-day)-caffeine(acute)/PC and caffeine(4-day)-caffeine(acute)/CC. Fourteen male recreationally-trained cyclists ingested capsules containing either placebo or caffeine (6 mg kg−1) for 4 days. On day 5 (acute), capsules containing placebo or caffeine (6 mg kg−1) were ingested 60 min before completing a 16 km time-trial (simulated cycling). CC and PC showed improvements in time (CC vs PP, Δ − 39.3 s and PC vs PP, Δ − 43.4 s; P = 0.00; ƞ2 = 0.33) and in output power (CC vs PP, Δ 5.55 w and PC vs PP, Δ 6.17 w; P = 0.00; ƞ2 = 0.30). At the final of the time-trial, CC and PC exhibited greater parasympathetic modulation (vagal tone) when compared to the PP condition (P < 0.00; ƞ2 = 0.92). Our study provided evidence that acute caffeine intake (6 mg∙kg−1) increased performance (time-trial) and demonstrated a relevant cardioprotective effect, through increased vagal tone.

Cardioprotective Effect of Pretreatment with A Single High-Dose Atorvastatin via Regulating Myocardial Uncoupling Protein 3 in a Rat Ischemia/Reperfusion Model

Objective: Since ischemia/reperfusion (I/R) can cause malignant arrhythmia, we explored the cardioprotective effect of pretreatment with a single and large dose of atorvastatin in the SD rat model. Methods: Rats were distributed into atorvastatin (Ator), I/R model and sham groups (n = 8/group) by random number table method. In Ator group, atorvastatin was gavaged with a single dose (80 mg/kg) 12 h before I/R. The heart was treated with ischemia for 30 min and then reperfusion for 2 h. Results: Myocardial infarct area was induced by I/R when compared with Sham group. Compared with I/R group, the pretreatment of atorvastatin significantly reduced area at risk/left ventricle (40.78 ± 1.39% vs. 46.76 ± 1.42%, p < 0.01), infarct area/area at risk (21.47 ± 1.65% vs. 29.16 ± 1.21%, p < 0.01), and lactate dehydrogenase activity (3056.17 ± 136.22 RFU vs. 3864.15 ± 162.92 RFU, p < 0.05). I/R induced uncoupling protein 3 (UCP3) in transcriptional and translational levels, but atorvastatin significantly increased the UCP3 expression when compared with I/R group, 1.91 ± 0.42 vs. 1.42 ± 0.21 fold (p < 0.05) in mRNA levels measured by RT-PCR and 2.07 ± 0.18 versus 1.45 ± 0.23 fold in protein levels by Western blots. Conclusion: A single high-dose atorvastatin pretreatment 12 h before I/R reduces the infarct area in I/R model in rats. The cardioprotection may be via regulating myocardial UCP3.