Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways

Yu, Yingli; Sun, Guibo; Luo, Yun; Wang, Min; Chen, Rongchang; Zhang, Jingyi; Ai, Qidi; Xing, Na

doi:10.1038/srep21730

Cited by 111 publications

(115 citation statements)

References 58 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…Continuous high glucose in DM induces oxidative stress and excessive ROS production. Accumulating studies have reported that the excessive ROS can cause the increase of lactate dehydrogenase (LDH) leakage and malondialdehvde (MDA) level, and simultaneously inhibit some antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) [9]. The above oxidants and antioxidants have become the common indicators to reflect the oxidative stress level.…”

Section: Introductionmentioning

confidence: 99%

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

et al. 2016

Self Cite

View full text Add to dashboard Cite

Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ischemic heart disease is a major cause of morbidity and mortality worldwide [1,2]. Clinical study has shown that sometimes reperfusion after ischemia can't improve the condition, and instead exacerbates the damage, which is known as myocardial ischemia/ reperfusion injury (MIRI) [3].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Yang

Wang

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…34,35 In perfused rat hearts submitted to a severe I/R injury (ischaemic period of 30 minutes or longer), the inhibition of the UPR by 4-PBA or TUDCA, decreased the number of apoptotic myocytes and diminished the infarct size, alleviating the deterioration of cardiac contractile function. 19,[36][37][38][39] In some cases, these beneficial effects were associated to a reduction in the oxidative stress. 19 The present results show for the first time that during a mild I/R injury, with minimal or no cell death, the inhibition of the ER stress response is also cardioprotective, suggesting that the UPR is contributing to the decline of the post-ischaemic mechanical performance of the stunned heart.…”

Section: Discussionmentioning

confidence: 99%

Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress

et al. 2019

View full text Add to dashboard Cite

Aim Myocardial ischaemia/reperfusion (I/R) produces structural and functional alterations depending on the duration of ischaemia. Brief ischaemia followed by reperfusion causes reversible contractile dysfunction (stunned heart) but long‐lasting ischaemia followed by reperfusion can result in irreversible injury with cell death. Events during I/R can alter endoplasmic reticulum (ER) function leading to the accumulation of unfolded/misfolded proteins. The resulting ER stress induces activation of several signal transduction pathways, known as unfolded protein response (UPR). Experimental evidence shows that UPR contributes to cell death in irreversible I/R injury; however, there is still uncertainty for its occurrence in the stunned myocardium. This study investigated the ER stress response and its functional impact on the post‐ischaemic cardiac performance of the stunned heart. Methods Perfused rat hearts were subjected to 20 minutes of ischaemia followed by 30 minutes of reperfusion. UPR markers were evaluated by qRT‐PCR and western blot. Post‐ischaemic mechanical recovery was measured in absence and presence of two chemical chaperones: tauroursodeoxycholic acid (TUDCA) and 4‐phenylbutyric acid (4‐PBA). Results Analysis of mRNA and protein levels of various ER stress effectors demonstrated that different UPR signalling cascades, involving both pro‐survival and pro‐apoptotic pathways, are activated. Inhibition of the UPR with chemical chaperones improved the post‐ischaemic recovery of cardiac mechanical function without affecting the I/R‐induced increase in oxidative stress. Conclusion Our results suggest that prevention of ER stress by chemical chaperones could be a therapeutic tool to limit deterioration of the contractile function in clinical settings in which the phenomenon of myocardial stunning is present.

show abstract

Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways

Cited by 111 publications

References 58 publications

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

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

Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress

Contact Info

Product

Resources

About