Total Saponins of Aralia Elata (Miq) Seem Alleviate Calcium Homeostasis Imbalance and Endoplasmic Reticulum Stress-Related Apoptosis Induced by Myocardial Ischemia/Reperfusion Injury

Abstract

Background/Aims: Total saponins of Aralia elata (Miq) Seem (AS) from the Chinese traditional herb Long ya Aralia chinensis L. reportedly provide cardioprotective effects, but the exact mechanisms require further study. Previous studies have showed that myocardial ischemia/ reperfusion injury (MIRI) was related to calcium homeostasis imbalance and endoplasmic reticulum stress (ERS). Thus, this study aimed to demonstrate protective effects of AS on MIRI. Methods: After administrating AS for 5 days, the left anterior descending artery coronary artery of Sprague-Dawley (SD) rats was ligated for 30 min. After 48 h of reperfusion, haemodynamics, Evans blue/ 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, masson staining and the levels of lactate dehydrogenase (LDH) and creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA) were detected to assess MIRI. ATPase activity and Western Blot were used to study the mechanisms. Results: Compared with IR group, AS treatment groups could significantly reduce myocardial infarct size; improve myocardial pathologic progress; decrease content of LDH, CK, and MDA; increase content of SOD; and restore the activities of Ca²⁺-Mg²⁺-ATPase, Na⁺-K⁺-ATPase, sarcoplasmic reticulum Ca²⁺-ATPases (SERCA), and calcineurin (CaN). AS treatment groups also significantly up-regulated the expression of GRP78, C/EBP homologous protein (CHOP), and Bax, and down-regulated the expression of Bcl-2, all similar to the effects of ERS. Conclusion: These findings illustrated that AS could prevent myocardial ischemia/reperfusion injury and reduce calcium homeostasis imbalance and ERS-related apoptosis.

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

“…However, Ca 2+ reuptake mediated by sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) may have been another important mechanism underlying the effects of DEX, as many studies showed that SERCA played an important role on the regulation of Ca 2+ homeostasis in myocardial I/R injury. [53][54][55] Third, the current results in H9c2 cardiomyocytes may not be fully extrapolated to animal models or even humans. Last, whether DEX-induced protection against I/R-induced injury is associated with the above-mentioned ion channels needs to be clarified in our future studies.…”

<p>Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress</p>

“…It has been well accepted that MIRI can lead to severe ERS, which is usually detected by upregulated GRP78 expression. 34,35 If ERS increases, apoptotic cascades would be considered an underlying mechanism of MIRI, pathway. [36][37][38] Moreover, ERS in MIRI can be alleviated through the suppression of caspase-12 and CHOP.…”

Biological Potential and Mechanism of Prodigiosin from Serratia marcescens Subsp. lawsoniana in Human Choriocarcinoma and Prostate Cancer Cell Lines

“…The tumor tissues were fixed in 4% PBS-formaldehyde and processed. Histological analysis of tumor tissues was performed according to the protocol described before [ 64 ]. Tissue sections were prepared on a Microm CM3050S (Leica, Wetzlar and Mannheim, Germany) with the microtome chamber chilled to −22 °C and the specimen holder set at −18 °C.…”

“…Tissue sections were prepared on a Microm CM3050S (Leica, Wetzlar and Mannheim, Germany) with the microtome chamber chilled to −22 °C and the specimen holder set at −18 °C. The sections were prepared at a thickness of 5 μm and then stained with hematoxylin-eosin (H&E) for microscopic observation (Leica IX71, Leica, Wetzlar and Mannheim, Germany) as described before [ 64 ]. Body weight was evaluated every two days and at the end of treatment.…”