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Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway

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Abstract

Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx against SAH-induced oxidative insults and the possible molecular mechanisms. Our data showed that Fx could significantly inhibit SAH-induced reactive oxygen species production and lipid peroxidation, and restore the impairment of endogenous antioxidant enzymes activities. In addition, Fx supplementation improved mitochondrial morphology, ameliorated neural apoptosis, and reduced brain edema after SAH. Moreover, Fx administration exerted an improvement in short-term and long-term neurobehavior functions after SAH. Mechanistically, Fx inhibited oxidative damage and brain injury after SAH by deacetylation of forkhead transcription factors of the O class and p53 via sirtuin 1 (Sirt1) activation. EX527, a selective Sirt1 inhibitor, significantly abated Fx-induced Sirt1 activation and abrogated the antioxidant and neuroprotective effects of Fx after SAH. In primary neurons, Fx similarly suppressed oxidative insults and improved cell viability. These effects were associated with Sirt1 activation and were reversed by EX527 treatment. Taken together, our study explored that Fx provided protection against SAH-induced oxidative insults by inducing Sirt1 signaling, indicating that Fx might serve as a potential therapeutic drug for SAH.

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Data Availability

The datasets generated and analyzed during this study are available from the corresponding author on reasonable request.

Abbreviations

8-OHdG:

8-Hydroxyguanosine

CAT:

Catalase

DCFH:

Dichlorodihydrofluorescein diacetate

DMSO:

Dimethylsulfoxide

EBI:

Early brain injury

Fx:

Fucoxanthin

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

HRP:

Horseradish peroxidase

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

MWM:

Morris water maze test

OxyHb:

Oxyhemoglobin

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SAH:

Subarachnoid hemorrhage

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

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Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (No. 81870922 for W.L., NO.81771291 for C.-H.H., No. 81971127 for Z.Z., 81901203 for Y.L.), Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health (No. JQX18001 for W.L.), Fundamental Research Funds for the Central Universities (No. 021414380361 for W. L.), Natural Science Research Project in Higher Education of Anhui Province (No. KJ2018A0253 for D.-Y.X.), and the Science Research Project of Professional personnel of the First Affiliated Hospital of Wannan Medical College (No. YR201911).

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Authors and Affiliations

  1. Department of Neurosurgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Xiang-Sheng Zhang & Cang Liu

  2. Department of Neurosurgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China

    Xiang-Sheng Zhang, Yue Lu, Tao Tao, Han Wang, Guang-Jie Liu, Xun-Zhi Liu, Chun-Hua Hang & Wei Li

  3. Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, China

    Da-Yong Xia

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Contributions

XSZ performed the studies and wrote the manuscript. HW and XZL participated in creating the experimental animal model. HW, DYX, and GJL contributed to the Western blotting and the immunofluorescence staining. TT, YL, and XSZ performed the in vitro studies. WL, CL, and HCH contributed to the design and analysis of the study and revised the manuscript. All authors analyzed the results and approved the final version of the manuscript.

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Correspondence to Wei Li.

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ESM 1

The purity of primary neuron. The particle analysis was performed by ImageJ and the purity of primary neuron was more than 90%. (PNG 459 kb)

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Zhang, XS., Lu, Y., Tao, T. et al. Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway. Mol Neurobiol 57, 5286–5298 (2020). https://doi.org/10.1007/s12035-020-02095-x

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