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Sinensetin Attenuates Amyloid Beta25-35-Induced Oxidative Stress, Inflammation, and Apoptosis in SH-SY5Y Cells Through the TLR4/NF-κB Signaling Pathway

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Abstract

Sinensetin (SIN) is an important active compound that exists widely in citrus plants, and has been reported to exhibit various pharmacological properties, including anti-oxidative, anti-inflammatory, and anti-tumor. This study was designed to examine whether SIN can protect against amyloid beta (Aβ)-induced neurotoxicity and to elucidate the underlying mechanism. Our results showed that pretreatment with SIN for 1 h, followed by co-treatment with Aβ plus SIN for 24 h, attenuated Aβ25-35-induced cell viability reduction, oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Aβ25-35-induced upregulation of Toll-like receptor 4 (TLR4) expression and nuclear translocation of nuclear factor-kappaB (NF-κB) p65 subunit were inhibited by pretreatment with SIN. Furthermore, the protective effect of SIN was abrogated by TLR4 overexpression. Hence, our data suggested that SIN attenuated Aβ25-35-induced neurotoxicity through the TLR4/NF-κB pathway.

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Author notes

  1. Zhongwen Zhi and Xiaohong Tang have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Huai’an Second People’s Hospital and The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, 223002, Jiangsu, People’s Republic of China

    Zhongwen Zhi, Yuqian Wang & Rui Chen

  2. Department of Neurology, Hongze Huai’an District People’s Hospital, Huai’an, 223100, Jiangsu, People’s Republic of China

    Xiaohong Tang

  3. Department of Neurology, Kangda College of Nanjing Medical University Affiliated Lianshui County People’s Hospital, 6 Hongri Avenue East, Lianshui County, Huai’an, 223400, Jiangsu, People’s Republic of China

    Hu Ji

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  1. Zhongwen Zhi
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Zhi, Z., Tang, X., Wang, Y. et al. Sinensetin Attenuates Amyloid Beta25-35-Induced Oxidative Stress, Inflammation, and Apoptosis in SH-SY5Y Cells Through the TLR4/NF-κB Signaling Pathway. Neurochem Res 46, 3012–3024 (2021). https://doi.org/10.1007/s11064-021-03406-x

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