Kalopanacis Cortex extract-capped gold nanoparticles activate NRF2 signaling and ameliorate damage in human neuronal SH-SY5Y cells exposed to oxygen–glucose deprivation and reoxygenation

Abstract

Recently, environment-friendly synthesis of gold nanoparticles (GNPs) has been extensively explored by biologists and chemists. However, significant research is still required to determine whether “eco-friendly” GNPs are beneficial to human health and to elucidate the molecular mechanisms of their effects on human cells. We used human neuronal SH-SY5Y cells to show that treatment with Kalopanacis Cortex extract-capped GNPs (KC-GNs), prepared via an eco-friendly, fast, one-pot synthetic route, protected neuronal cells against oxygen–glucose deprivation/reoxygenation (OGD/R)-induced damage. To prepare GNPs, Kalopanacis Cortex was used without any chemical reducing and stabilizing agents. Ultraviolet–visible spectroscopy showed maximum absorbance at 526 nm owing to KC-GN surface plasmon resonance. Hydrodynamic size (54.02±2.19 nm) and zeta potential (−20.3±0.04 mV) were determined by dynamic light scattering. The average diameter (41.07±3.05 nm) was determined by high-resolution transmission electron microscopy. Energy-dispersive X-ray diffraction spectroscopy and X-ray diffraction confirmed the presence of assembled GNPs. Fourier transform infrared analysis suggested that functional groups such as O–H, C–C, and C–N participated in KC-GN formation. Cell viability assays indicated that KC-GNs restored the viability of OGD/R-treated SH-SY5Y cells. Flow cytometry demonstrated that KC-GNs inhibited the OGD/R-induced reactive oxygen species production and mitochondrial membrane potential disruption. KC-GNs also inhibited the apoptosis of OGD/R-exposed cells. Western blot analysis indicated that the OGD/R-induced cellular apoptosis and simultaneous increases in the expression of cleaved caspase-3, p53, p21, and B-cell lymphoma 2-associated X protein were reversed by KC-GNs. The KC-GN-mediated protection against OGD/R-induced neurotoxicity was diminished by NRF2 and heme oxygenase-1 gene knockdowns. Collectively, these results suggested that KC-GNs exerted strong neuroprotective effects on human neuronal cells, which might be attributed to the attenuation of OGD/R-induced neuronal cell injury through the NRF2 signaling pathway.

Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

“…One study in undifferentiated SH-SY5Y cells showed that the mitochondrial permeability transition pore is opened with OGD by translocation of P53 to mitochondria and activation of Cyclophilin D (Zhao et al 2013 ). The consequent mitochondrial membrane depolarization has been found in undifferentiated SH-SY5Y cells (n = 3) (Agudo-Lopez et al 2010 ; Park et al 2017 ; Wang et al 2018b ). Mitochondrial membrane permeabilization by opening of the mitochondrial permeability transition pore and loss of the mitochondrial membrane potential (MMP) has also been established in three studies in undifferentiated and in two studies differentiated SH-SY5Y cells (Lin et al 2020 ; Liu et al 2019a ; Park et al 2017 ; Sriwastva et al 2020 ; Wang et al 2019b ).…”

“…The consequent mitochondrial membrane depolarization has been found in undifferentiated SH-SY5Y cells (n = 3) (Agudo-Lopez et al 2010 ; Park et al 2017 ; Wang et al 2018b ). Mitochondrial membrane permeabilization by opening of the mitochondrial permeability transition pore and loss of the mitochondrial membrane potential (MMP) has also been established in three studies in undifferentiated and in two studies differentiated SH-SY5Y cells (Lin et al 2020 ; Liu et al 2019a ; Park et al 2017 ; Sriwastva et al 2020 ; Wang et al 2019b ). Normal mitochondrial function was reduced in undifferentiated SH-SY5Y cells after OGD (Herrmann et al 2013 ).…”

“…NRF-2 and other cytoprotective enzymes have been investigated in seven studies using undifferentiated SH-SY5Y cells. The results showed increased expression of NRF-2 (Lin-Holderer et al 2016 ; Liu et al 2019b ; Park et al 2017 ; Ruan et al 2020 ; Shi et al 2019 ; Wang and Xu 2021 ; Zhi et al 2020 ) and the cytoprotective enzymes NAD(P)H dehydrogenase [quinone] 1 (NQO1) and hemeoxygenase-1 (HO-1) (Liu et al 2019b ; Park et al 2017 ; Ruan et al 2020 ; Shi et al 2019 ; Wang and Xu 2021 ; Zhi et al 2020 ) after ischemia/hypoxia.…”

“…Cell death is a much studied final common path in human neuronal in vitro models of cerebral ischemia. A total of 59 studies in undifferentiated (Agudo-Lopez et al 2010 ; Castri et al 2014 ; Chen et al 2019 ; Dong et al 2019 , 2021 ; Du et al 2012 ; Feng et al 2021 ; Gao et al 2017 , 2020 ; He et al 2014 ; Hu et al 2020 ; Huang et al 2018 , 2021 ; Jia et al 2021 ; Lee et al 2013 ; Li and Ma 2020 ; Li et al 2020a ; Liu et al 2019b ; Lu et al 2019 ; Luan et al 2013 ; Marutani et al 2012 ; Meng et al 2021 ; Nampoothiri and Rajanikant 2019 ; Niu et al 2018 ; Park et al 2017 ; Ruan et al 2020 ; Shan et al 2022 ; Shi et al 2021 ; Song et al 2019 ; Tian et al 2020 ; Wang et al 2013 , 2017 , 2018b , c , 2019b , c , 2020b , 2021a , b ; Wang and Xu 2021 ; Wen et al 2020 ; Wu et al 2020a , b ; Xing et al 2021 ; Xu et al 2020a , b ; Yan et al 2015 , 2020 ; Yang et al 2014 , 2021a ; Yao et al 2019 ; Yi et al 2020 ; Zappala et al 2021 ; Zhang et al 2016a , b ,…”

“…In SH-SY5Y and SK-N-SH cell models, cell death rate after ischemia/hypoxia has been investigated extensively. Eighty-three papers found increased cell death rates after ischemia/hypoxia in undifferentiated SH-SY5Y cells (Castri et al 2014 ; Chan et al 2015 ; Chang et al 2017 ; Chen 2004 ; Chen et al 2019 ; Dong et al 2019 ; Fang et al 2020 ; Feng et al 2021 ; Formisano et al 2013 ; Gao et al 2017 , 2020 ; Guo et al 2018 , 2019 ; Hong et al 2017 ; Hsieh et al 2021 ; Hu et al 2020 ; Huang et al 2018 , 2021 ; Janssen et al 2021 ; Jia et al 2021 ; Jimenez-Almarza et al 2019 ; Karuppagounder et al 2013 ; Landgraf et al 2020 ; Li et al 2019b , 2020b ; Lin-Holderer et al 2016 ; Liu 2016 ; Liu et al 2016 , 2018 , 2019b ; Lu et al 2019 ; Luan et al 2013 ; Marmol et al 2021 ; Marutani et al 2012 ; McCune et al 2016 ; Meng et al 2021 ; Nampoothiri and Rajanikant 2019 ; Niu et al 2018 ; Park et al 2017 ; Roy et al 2021 ; Ruan et al 2020 ; Shi et al 2016 , 2020 , 2021 ; Sinoy et al 2017 ; Song et al 2019 ; Tajes et al 2013 ; Tan et al 2021 ; Tang et al 2013 ; Tian et al 2020 ; Wang et al 2013 , 2018b , c ...…”