Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein

Abstract

Astragaloside IV (ASI), a traditional Chinese medicine, is a main active ingredient of Astragalus membranaceus. Many clinical studies have found that ASI protects cardiomyocytes in cardiovascular diseases, but the underlying mechanisms remain obscure. The aim of this study was to investigate the molecular mechanisms responsible for the protective effects of ASI in cardiomyocytes from anoxia/reoxygenation (A/R) injury. According to the previous studies, we hypothesized that the cardioprotective effects of ASI against A/R injury might be associated with Notch1/Hes1 signaling pathway. In this study, neonatal rat primary cardiomyocytes were preconditioned with ASI prior to A/R injury. Our results showed that ASI effectively increased the cell viability, decreased the content of MDA, decreased the activities of CPK and LDH, increased the activities of GSH-Px and SOD, and reduced the reactive oxygen species (ROS) generation and the loss of mitochondrial membrane potential (Δψm). ASI inhibited the mitochondrial permeability transition pore (mPTP) opening and activation of caspase-3, and finally decreased the cell apoptosis in cardiomyocytes. Furthermore, ASI upregulated Hes1 protein expression. However, pretreatment with DAPT, a Notch1 inhibitor, effectively attenuated the cardioprotective effects of ASI against A/R injury, except MDA, SOD, GSH-Px, and the ROS generation. Taken together, we demonstrated that ASI could protect against A/R injury via the Notch1/Hes1 signaling pathway.

p53/Drp1-dependent mitochondrial fission mediates aldosterone-induced podocyte injury and mitochondrial dysfunction

“…Mitochondrial membrane potential is essential for an integrated appraisal of mitochondrial function (30). The loss of mitochondrial membrane potential is mediated by the MPTP opening, resulting in the release of cytochrome c from mitochondria (15). Our present data showed that mitochondrial fission inhibition suppressed aldosterone-induced MPTP opening and mitochondrial membrane potential loss.…”

Vanillic Acid Alleviates Acute Myocardial Hypoxia/Reoxygenation Injury by Inhibiting Oxidative Stress

“…H9c2 cells were incubated at 37°C in a 5% CO 2 incubator (Forma™ 310, Thermo Fisher, USA) with high glucose (4.5 g/l glucose) DMEM (Solarbio, Beijing, China) by adding 13% FBS (foetal bovine serum, WISENT, Canada) and antibiotics (100 U/ml penicillin and 100 μg/ml streptomycin, Solarbio, Beijing, China). The hypoxia/reoxygenation (H/R) cell model was set up to imitate an ischaemia/reperfusion (I/R) model in vitro [14][15][16][17]. Briefly, after different pretreatments, H9c2 cells were cultured in hypoxic solution (sodium lactate 40 mM, NaH 2 PO 4 0.9 mM, NaHCO 3 6 mM, MgSO 4 1.2 mM, HEPES 20 mM, CaCl 2 1.8 mM, NaCl 98.5 mM, KCl 10 mM, pH 6.8) and incubated at 37°C with 5% CO 2 and 0.1% O 2 in a hypoxic chamber (Proox model C21, BioSpherix Ltd., USA) for 3 h. H9c2 cells were subsequently cultured in reoxygenation solution (glucose 5.5 mM, NaH 2 PO 4 0.9 mM, NaHCO 3 20 mM, MgSO 4 1.2 mM, HEPES 20 mM, CaCl 2 1.8 mM, NaCl 129.5 mM, KCl 5 mM, pH 7.4) and incubated at 37°C and 95% O 2 /5% CO 2 in a reoxygenation chamber for 2 h. All experiments were performed in triplicate.…”

Astragaloside IV Regulates the PI3K/Akt/HO-1 Signaling Pathway and Inhibits H9c2 Cardiomyocyte Injury Induced by Hypoxia–Reoxygenation

“…1) In recent years, in vitro and in vivo studies have shown that AS-IV is protective against myocardial ischemiareperfusion injury (IRI) 2,3) and its mechanism of action is mainly related to anti-oxidative stress and anti-inflammatory pathways. [4][5][6] However, the specific target molecules and signaling pathways involved still await further study. Heme oxygenase (HO-1) is recognized as an important anti-oxidative stress and tissue protective enzyme that produces CO and biliverdin, and can also induce multiple anti-oxidative and anti-inflammatory signaling pathways, which significantly reduce cellular damage and protect organ function.…”