Dihydromyricetin protects against cerebral ischemia/reperfusion injury via suppressing microglia-mediated neuroinflammation and activation of ERK1/2-CREB signaling pathway

Zhao, Yizheng; Wang, Panpan; Chen, Shuangshuang; Han, Chaojun; Yan, Qiuting; Zheng, Longtai; Jia, Jia; Ren, Zhaoxiang; Zhen, Xuechu

doi:10.1016/j.jff.2017.03.034

Cited by 17 publications

(5 citation statements)

References 35 publications

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“…These pathological changes, in turn, cause cell membrane, mitochondrial, and DNA damage, and the subsequent immune responses induce necrosis and apoptosis (Hou et al 2018). Microglia are the rst cell population to respond to ischemic stroke (Zhao et al 2017) and are activated within minutes to secrete relevant protective factors (Su et al 2017). Regulation of the moderate in ammatory response of microglia is one of the key measures to protect the ischemic penumbra after stroke (Xiang et al 2019).…”

Section: Discussionmentioning

confidence: 99%

The influence of ferroptosis on the in vitro OGD/R model in rat microglia

Zhang

et al. 2023

Preprint

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Cerebral ischemia-reperfusion injury causes high mortality and incidence of disability in patients. We aimed to explore the influence of ferroptosis on an oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary rat microglia. Primary microglia were extracted from rats and cultured in vitro. The cells were subjected to a hypoxic environment for 6 h in a glucose-free medium, and then re-oxygenated for 24 h in DMEM/F12. Rat microglia were pretreated with the ferroptosis activator erastin and the ferroptosis inhibitor ferrostatin 1 for 24 h, followed by detection of cell cycle progression and apoptosis by flow cytometry. Intracellular total iron levels were measured. In addition, the relative levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined using enzyme-linked immunosorbent assay. The protein levels of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 were examined by western blotting. Compared with rat microglia subjected to OGD/R, pretreatment with erastin did not influence cell apoptosis but significantly enhanced total iron levels, MDA, and ROS levels, whereas it reduced SOD levels. Moreover, it upregulated ACSL4, TFR1, and 15-lox2 and downregulated GPX4 and SLC7A11. Pretreatment with ferrostatin 1 significantly inhibited cell apoptosis and cell cycle arrest in the G0/G1 phase. It significantly reduced total iron levels, MDA, and ROS levels and enhanced SOD levels, which also downregulated ACSL4, TFR1, and 15-lox2, and upregulated GPX4 and SLC7A11. Our study showed that inhibition of ferroptosis is favorable against potential OGD/R-induced damage in rat microglia.

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Section: Discussionmentioning

confidence: 99%

The influence of ferroptosis on the in vitro OGD/R model in rat microglia

Zhang

et al. 2023

Preprint

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“…The chronic application of the neuroprotective agent DHM has been shown to produce powerful neuroprotective effects in models of different diseases, including PD and stroke [ 13 , 27 ]. As a traditional Chinese medicine, it was initially used to treat cough and fever and later found to have many pharmacological effects, such as protective effects on the heart, diabetes, liver, and nervous system, possibly through reducing oxidative stress or anti-inflammation [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of an inducible Dicer conditional knockout mouse model of Parkinson’s disease: validation of the antiparkinsonian effects of a sigma-1 receptor agonist and dihydromyricetin

et al. 2020

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Parkinson’s disease (PD) is a common neurodegenerative disease characterized by motor impairment and progressive loss of dopamine (DA) neurons. At present, the acute application of neurotoxic drugs such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are commonly used to simulate the pathology of PD; however, it is difficult to induce the progressive pathogenesis of PD with these models. In this study, we employed DAT promoter-mediated Cre transgenic mice to establish tamoxifen-inducible Dicer conditional knockout (cKO) mice in an effort to mimic the progressive loss of DA neurons and the development of PD-like behavioral phenotypes. The results showed that Dicer cKO mice exhibited progressive loss of DA neurons in the substantia nigra (SN) following tamoxifen administration. Significant DA loss was observed 6 weeks after tamoxifen administration; accordingly, progressive motor function impairment was also observed. We also found that a significant neuroinflammatory response, as evidenced by microglial proliferation, another hallmark of PD pathogenesis, accompanied the loss of DA neurons. The acute application of levo-DOPA ( l -DOPA) relieved the PD-like motor impairments in Dicer cKO mice to exert its antiparkinsonian action, indicating that the model can be used to evaluate the antiparkinsonian efficacy of PD drugs. To further elucidate the potential application of this novel PD animal model for PD drug development, we employed the powerful neuroprotective agent dihydromyricetin (DHM) (10 mg/kg) and the selective sigma-1 receptor agonist PRE-084 (1 mg/kg), both of which were previously shown to produce antiparkinsonian effects. The results indicated that the chronic administration of either DHM or PRE-084 attenuated the Dicer cKO-induced loss of DA neurons and motor impairments, although the two drugs acted through different mechanisms. These data indicate that the Dicer cKO mouse model may be a useful model for investigating the pathological development of PD and intervention-mediated changes. In conclusion, this transgenic mouse model appears to simulate the progressive pathogenesis of PD and may be a potentially useful model for PD drug discovery.

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“…RNA was extracted from the A549 cells after 48 h incubated with CPU micelle and siRNA–CPU micelle, and PBS using TRIzol reagent (TaKaRa Biotechnology, Dalian, China) was used to extract total RNA from A549. Then, 1000 ng of total RNA was reversed in accordance with the manufacturer’s instructions. , mRNA expression quantitative tests were performed by SYBR Premix II (Bio-Rad, Hercules, CA, USA). GAPDH was used as the endogenous control.…”

Section: Methodsmentioning

confidence: 99%

“…Then, 1000 ng of total RNA was reversed in accordance with the manufacturer's instructions. 40,41 mRNA expression quantitative tests were performed by SYBR Premix II (Bio-Rad, Hercules, CA, USA). GAPDH was used as the endogenous control.…”

Section: Dox Distribution In Tumor Spheroids and Solidmentioning

confidence: 99%

Nucleolin-Targeting AS1411-Aptamer-Modified Graft Polymeric Micelle with Dual pH/Redox Sensitivity Designed To Enhance Tumor Therapy through the Codelivery of Doxorubicin/TLR4 siRNA and Suppression of Invasion

et al. 2017

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In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4-siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox-siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Furthermore, the micelles loaded with TLR4-siRNA inhibited the migration and invasion of A549. Excellent tumor penetrating efficacy was also noted in the A549 tumor spheroids and solid tumor slices. In vivo, multiple results demonstrated the excellent tumor-targeting ability of AS1411-chitosan-ss-polyethylenimine-urocanic acid (ACPU) micelle in tumor tissues. The micelles exhibited excellent antitumor efficacy and low toxicity in the systemic circulation in lung-tumor-bearing BALB/c mice. These results conclusively demonstrated the great potential of the new graft copolymer micelle with targeting function for the targeted and efficient codelivery of chemotherapeutic drugs and genes in cancer treatment.

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Dihydromyricetin protects against cerebral ischemia/reperfusion injury via suppressing microglia-mediated neuroinflammation and activation of ERK1/2-CREB signaling pathway

Cited by 17 publications

References 35 publications

The influence of ferroptosis on the in vitro OGD/R model in rat microglia

The influence of ferroptosis on the in vitro OGD/R model in rat microglia

Development and characterization of an inducible Dicer conditional knockout mouse model of Parkinson’s disease: validation of the antiparkinsonian effects of a sigma-1 receptor agonist and dihydromyricetin

Nucleolin-Targeting AS1411-Aptamer-Modified Graft Polymeric Micelle with Dual pH/Redox Sensitivity Designed To Enhance Tumor Therapy through the Codelivery of Doxorubicin/TLR4 siRNA and Suppression of Invasion

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