SIRT1/PGC-1α signaling activation by mangiferin attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells.

Abstract

Ischemia reperfusion injury (IRI) is associated with poor prognoses in the setting of ischemic brain diseases. Silence information regulator 1 (SIRT1) is a member of the third class of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins. Recently, the role of SIRT1/peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α) pathway in organ (especially the brain) protection under various pathological conditions has been widely investigated. Mangiferin (MGF), a natural C-glucosyl xanthone polyhydroxy polyphenol, has been shown to be beneficial to several nervous system diseases and the protective effects of MGF can be achieved through the regulation of SIRT1 signaling. This study is designed to investigate the protective effects of MGF treatment in the setting of cerebral IRI and to elucidate the potential mechanisms. We first evaluated the toxicity of MGF and chose the safe concentrations for the following experiments. MGF exerted obvious neuroprotection against hypoxia/reoxygenation (HR)-induced injury, indicated by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release and reactive oxygen species generation. MGF also restored the protein expressions of SIRT1, PGC-1α, Nrf2, NQO1, HO-1, NRF1, UCP2, and Bcl2 down-regulated by HR treatment. However, SIRT1 siRNA could reverse MGF-induced neuroprotection and decrease the expressions of molecules mentioned above. Taken together, our findings suggest that MGF treatment exerts neuroprotection against HR injury via activating SIRT1/PGC-1α signaling. These findings may provide a theoretical basis for the exploitation of MGF as a potential neuroprotective drug candidate, which may be beneficial for the ischemic stroke patients in clinic.

• Authors: Mengfan Chen, Zheng Wang, Wenying Zhou, Chenxi Lu, Ting Ji, Wenwen Yang, Zhenxiao Jin, Ye Tian, Wangrui Lei, Songdi Wu, Qi Fu, Zhen Wu, Xue Wu, Mengzhen Han, Minfeng Fang, Yang Yang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 907 Pg. 174236 (Sep 15 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34116043 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Xanthones
• mangiferin
• xanthone
• Sirtuin 1

Topics

• Humans
• Male
• Sirtuin 1
• Xanthones