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Free Radic Biol Med. 2018 Aug 20;124:504-516. doi: 10.1016/j.freeradbiomed.2018.06.035. Epub 2018 Jun 30.

Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways.

Author information

1
Department of Neurosurgery, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China; Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
3
Department of Neurosurgery, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
4
Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5
Department of Neurosurgery, Changzheng Hospital, School of Medicine, Second Military Medical University, Shanghai, China.
6
Department of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
7
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China. Electronic address: zhangxsp@163.com.
8
Department of Neurosurgery, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China. Electronic address: hang_neurosurgery@163.com.
9
Department of Anesthesiology and Critical Care Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jwang79@jhmi.edu.

Abstract

Salvianolic acid B (SalB), a natural polyphenolic compound extracted from the herb of Salvia miltiorrhiza, possesses antioxidant and neuroprotective properties and has been shown to be beneficial for diseases that affect vasculature and cognitive function. Here we investigated the protective effects of SalB against subarachnoid hemorrhage (SAH)-induced oxidative damage, and the involvement of underlying molecular mechanisms. In a rat model of SAH, SalB inhibited SAH-induced oxidative damage. The reduction in oxidative damage was associated with suppressed reactive oxygen species generation; decreased lipid peroxidation; and increased glutathione peroxidase, glutathione, and superoxide dismutase activities. Concomitant with the suppressed oxidative stress, SalB significantly reduced neurologic impairment, brain edema, and neural cell apoptosis after SAH. Moreover, SalB dramatically induced nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased expression of heme oxygenase-1 and NADPH: quinine oxidoreductase-1. In a mouse model of SAH, Nrf2 knockout significantly reversed the antioxidant effects of SalB against SAH. Additionally, SalB activated sirtuin 1 (SIRT1) expression, whereas SIRT1-specific inhibitor sirtinol pretreatment significantly suppressed SalB-induced SIRT1 activation and Nrf2 expression. Sirtinol pretreatment also reversed the antioxidant and neuroprotective effects of SalB. In primary cultured cortical neurons, SalB suppressed oxidative damage, alleviated neuronal degeneration, and improved cell viability. These beneficial effects were associated with activation of the SIRT1 and Nrf2 signaling pathway and were reversed by sirtinol treatment. Taken together, these in vivo and in vitro findings suggest that SalB provides protection against SAH-triggered oxidative damage by upregulating the Nrf2 antioxidant signaling pathway, which may be modulated by SIRT1 activation.

KEYWORDS:

Nrf2; Oxidative damage; Salvianolic acid B; Sirtuin 1; Subarachnoid hemorrhage

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