Tetrahydroxystilbene Glucoside (TSG) Restores the Effect of Transient Hypoxia on Reperfusion Injury in Senescent H9c2 Cells by Regulating Mitochondrial Energy Metabolism.

Yin Cheng,Jia Song,Yun Zhu,Pengfei Hu

doi:10.1155/2018/2545024

Abstract

Tetrahydroxystilbene glucoside (TSG) is extracted from a famous Chinese herbal medicine which is widely used as an antiaging agent in history. Lots of studies gave evidence that TSG exhibited benefits to brain, like improvement of learning and memory and synaptic plasticity. Moreover, the polyphenolic structure of TSG enables its capability to prevent cerebral ischemia/reperfusion injury (IRI) by reducing apoptosis and ROS/RNS generation. Due to its antioxidant profile, TSG had been demonstrated to alleviate cardiac toxicity by regulating biochemical indexes and ROS. However, whether TSG exhibited cardioprotective effects via mitochondrial energy metabolic functions, which played crucial role in IRI, remained unclear. Here, we used an in vitro aging model of cardiomyocytes to evaluate the effects of TSG on transient hypoxia-pretreated hypoxia/reoxygenation (H/R) injury and mitochondrial energy metaolism. Our results showed that TSG enhanced cardioprotective effect of transient hypoxia on H/R by reducing excessive ROS production and calcium overloading. Significant improvements of mitochondrial respiratory functions and ketone body metabolism elucidated that TSG restored the effect of transient hypoxia on H/R injury in aging cardiomyocytes via upregulating mitochondrial energy metabolism.

Highlights

Ischemic preconditioning (IPC), targeting to mitochondrial ATP-sensitive potassium channel (KATP channel), was one of the effective clinical/experimental interventions to prevent ischemia/reperfusion injury (IRI) [1]
Whether tetrahydroxystilbene glucoside (TSG) can restore the effect of transient hypoxia on long-term H/R injury in senescent H9c2 cells was tested in our study
Combined treatment of HYP and TSG showed an increasing cell viability and mitochondrial viability comparing with control group, indicating TSG could restore the cardioprotective effect of HYP

Summary

Introduction

Ischemic preconditioning (IPC), targeting to mitochondrial ATP-sensitive potassium channel (KATP channel), was one of the effective clinical/experimental interventions to prevent ischemia/reperfusion injury (IRI) [1]. The neuroprotective effects of TSG had shown that TSG significantly reduced cognitive impairments and improved the hippocampal synaptic plasticity [7, 9], and further improved brain memory by activating SIRT1 expression and phosphorylation of ERKs, CaMKII [10] Depending on these activities, TSG intervention restored learning memory in APP transgenic mice, a mouse model of Alzheimer’s disease, and increased neuron survival in Parkinson’s mice via PI3K/Akt signaling [11, 12]. Based on the beneficial effects of TSG on brain, Chen’s group found pretreatment of TSG prevented cerebral ischemia injury via inhibition of ROS/RNS generation, involving JNK and NF-κB signaling [13] All of these studies indicated TSG probably have beneficial effect on cardiac IPC against prolonged I/R injury in aging hearts

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Conclusion