Protective effect of Astragaloside IV on chronic intermittent hypoxia-induced vascular endothelial dysfunction through the calpain-1/SIRT1/AMPK signaling pathway

Abstract

Vascular endothelial dysfunction (VED) is linked with the pathogenesis of obstructive sleep apnea (OSA) comorbidities, such as cardiovascular disease. Astragaloside IV (As-IV) has exhibited significant improvement for endothelial dysfunction. Nonetheless, the protective mechanism is not clear. Therefore, the present study investigated the potential mechanism of As-IV on VED. Calpain-1 knockout and wild-type C57BL/6 mice exposed to chronic intermittent hypoxia (CIH) were established and treated with As-IV (40, 80 mg/kg) for 4 weeks. Human coronary artery endothelial cells (HCAECs) subjected to CIH exposure were pretreated with As-IV, MDL-28170 (calpain-1 inhibitor) and SRT1720 (SIRT1 activator) for 48 h in vitro. The endothelial function, inflammation, oxidative stress and mitochondrial function were measured to evaluate VED. Our data revealed that As-IV treatment ameliorated CIH-induced endothelial-dependent vasomotion and augmented nitric oxide (NO) production. As-IV administration suppressed the secretion of inflammation, oxidative stress and mitochondrial dysfunction. As-IV treatment reduced the expression of calpain-1 and restored the downregulated expression of SIRT1 and Thr172 AMPK and Ser1177 eNOS phosphorylation. The effects of calpain-1 knockout and SRT1720 were similar to the effect of As-IV on VED. These findings demonstrated that As-IV ameliorated VED induced by chronic intermittent hypoxia via the calpain-1/SIRT1/AMPK signaling pathway.

Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea

“…It is important to observe that many molecules have only been tested in mouse models, such as Astragaloside IV, which showed an improvement of hypoxia-induced endothelial function [ 97 ]; Tauroursodeoxycholic acid, against hepatic damage induced by HI [ 98 ]; Pitavastatin, showing a reversal of IH-induced myocardial hypertrophy, cardiac function, perivascular fibrosis and inflammatory indices [ 99 ]; Allopurinol also showed beneficial effects in mouse models of OSAS with a reduction of lipid peroxidation and an improvement in cardiac function [ 100 ]; and for all molecules, clinical trials are needed.…”

Integrated transcriptomics, proteomics and metabolomics to identify biomarkers of astragaloside IV against cerebral ischemic injury in rats

“…[35][36][37][38] Although few literature reports exist on Me2 in cerebral ischemia, it is associated with multiple molecular mechanisms of cerebral ischemic injury, so Me2 is also considered a potential target for future research. Researchers have found some signal pathways about AS-IV against cerebral ischemic injury, and AS-IV inhibited the occurrence of oxidative stress and mitochondrial dysfunction through the calpain-1/SIRT1/AMPK signal pathway; 39 AS-IV stimulates angiogenesis through the PI3K/Akt pathway. 40 These are similar to the molecular mechanisms of Me2 regulation.…”

Pretreatment of kaempferol-3-O-rutinoside protects H9c2 cells against LPS-induced inflammation through the AMPK/SIRT1 pathway

“…AMPK exists in the form of α, β, and γ, and is directly activated by interaction between Sestrin1 and Thr 172, which have been demonstrated in cardiomyocytes (Yuan et al, 2022). When activated, AMPK maintains cell energy balance, turning on the productive catabolic pathway while shutting down the energy-consuming synthetic pathway, which contributes to cell survival and cardiovascular system function when cells are hypoxic (Wu and Zou, 2020;Zhao et al, 2022). Studies have shown that normal energy metabolism of the myocardium is the material basis for maintaining the stability of cardiac internal environment and myocardial systolic function.…”