Hyperoside alleviates epilepsy-induced neuronal damage by enhancing antioxidant levels and reducing autophagy

Cao, Jianwen; Tang, Chengxuan; Gao, Manman; Rui, Yanggang; Zhang, Jie; Wang, Li; Wang, Yang; Xu, Bo; Yan, Bing Chun

doi:10.1016/j.jep.2020.112884

Cited by 40 publications

(22 citation statements)

References 61 publications

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“…Hyperoside (quercetin3-O- β -D-galactoside) is an active compound isolated from Hypericum plants. It has antioxidant and anti-inflammatory activities, decreasing calcium overload and inhibiting apoptosis [ 9 , 10 ]. Previous studies have confirmed that hyperoside effectively prevents neurological complications caused by neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

et al. 2021

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Neuroinflammation plays important roles in the pathogenesis and progression of altered neurodevelopment, sensorineural hearing loss, and certain neurodegenerative diseases. Hyperoside (quercetin-3-O-β-D-galactoside) is an active compound isolated from Hypericum plants. In this study, we investigate the protective effect of hyperoside on neuroinflammation and its possible molecular mechanism. Lipopolysaccharide (LPS) and hyperoside were used to treat HT22 cells. The cell viability was measured by MTT assay. The cell apoptosis rate was measured by flow cytometry assay. The mRNA expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were determined by quantitative reverse transcription polymerase chain reaction. The levels of oxidative stress indices superoxide dismutase (SOD), reactive oxygen species (ROS), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured by the kits. The expression of neurotrophic factor and the relationship among hyperoside, silent mating type information regulation 2 homolog-1 (SIRT1) and Wnt/β-catenin, and sonic hedgehog was examined by western blotting. In the LPS-induced HT22 cells, hyperoside promotes cell survival; alleviates the level of IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax, and caspase-3; and increases the expression of CAT, SOD, GSH, Bcl-2, BDNF, TrkB, and NGF. In addition, hyperoside upregulated the expression of SIRT1. Further mechanistic investigation showed that hyperoside alleviated LPS-induced inflammation, oxidative stress, and apoptosis by upregulating SIRT1 to activate Wnt/β-catenin and sonic hedgehog pathways. Taken together, our data suggested that hyperoside acts as a protector in neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

et al. 2021

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“…As a flavonoid, hyperoside has many physiological properties, such as anti-inflammatory, antispasmodic, diuretic, and antitussive properties, and can lower blood pressure, lower cholesterol, and protect the heart and cerebral blood vessels; thus, it is an important natural product. The development of new varieties of okra with increased hyperoside content has an important impact on the medical and economic benefits of the plant 54 – 56 . This research lays a molecular foundation for the development of fine varieties of okra and provides a new research direction related to flower development in other non-model plants.…”

Section: Discussionmentioning

confidence: 99%

Hyperoside promotes pollen tube growth by regulating the depolymerization effect of actin-depolymerizing factor 1 on microfilaments in okra

et al. 2021

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Mature pollen germinates rapidly on the stigma, extending its pollen tube to deliver sperm cells to the ovule for fertilization. The success of this process is an important factor that limits output. The flavonoid content increased significantly during pollen germination and pollen tube growth, which suggests it may play an important role in these processes. However, the specific mechanism of this involvement has been little researched. Our previous research found that hyperoside can prolong the flowering period of Abelmoschus esculentus (okra), but its specific mechanism is still unclear. Therefore, in this study, we focused on the effect of hyperoside in regulating the actin-depolymerizing factor (ADF), which further affects the germination and growth of pollen. We found that hyperoside can prolong the effective pollination period of okra by 2–3-fold and promote the growth of pollen tubes in the style. Then, we used Nicotiana benthamiana cells as a research system and found that hyperoside accelerates the depolymerization of intercellular microfilaments. Hyperoside can promote pollen germination and pollen tube elongation in vitro. Moreover, AeADF1 was identified out of all AeADF genes as being highly expressed in pollen tubes in response to hyperoside. In addition, hyperoside promoted AeADF1-mediated microfilament dissipation according to microfilament severing experiments in vitro. In the pollen tube, the gene expression of AeADF1 was reduced to 1/5 by oligonucleotide transfection. The decrease in the expression level of AeADF1 partially reduced the promoting effect of hyperoside on pollen germination and pollen tube growth. This research provides new research directions for flavonoids in reproductive development.

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“…In rodent models of KA-or PTZ-induced epilepsy, increased levels of seizure behavior, microglial activation markers (Iba-1, TNF-α, IL-1β, IL-6, iNOS, and COX-2), NF-κB activation, apoptosis-related proteins (Bax and caspase-3/8/9) and ROS were confirmed in the hippocampus [48,61,[72][73][74][75][76]. Furthermore, decreased levels of NeuN and Bcl-2 expression and AKT and CREB phosphorylation were confirmed in the hippocampus or cortices of rodents [71,77,78]. A significant increase in the interaction of microglia and neurons was confirmed by KA administration [54].…”

Section: Experimental Animal Models Of Epilepsymentioning

confidence: 98%

Section: Experimental Animal Models Of Epilepsymentioning

confidence: 99%

“…It was recently introduced that compounds isolated from natural products [77], antioxidants [74] and agonists [19,54,80], exerted protective effects in epileptic studies. Hyperoside from Hypericum perforatum L. inhibited neuronal damage through upregulating the expression of antioxidant proteins [77]. The antioxidants asiatic acid and maslinic acid exerted protective effects against KA-induced neuroinflammation and oxidative stress by regulating inflammatory molecules, apoptosis-related molecules, and ROS/oxidized glutathione (GSSG) [74].…”

Section: Experimental Animal Models Of Epilepsymentioning

confidence: 99%

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The Role of Microglia in the Development of Neurodegenerative Diseases

et al. 2021

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Microglia play an important role in the maintenance and neuroprotection of the central nervous system (CNS) by removing pathogens, damaged neurons, and plaques. Recent observations emphasize that the promotion and development of neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize the contribution of microglial activation and its associated mechanisms in NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), based on recent observations. This review also briefly introduces experimental animal models of epilepsy, AD, PD, and HD. Thus, this review provides a better understanding of microglial functions in the development of NDs, suggesting that microglial targeting could be an effective therapeutic strategy for these diseases.

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Hyperoside alleviates epilepsy-induced neuronal damage by enhancing antioxidant levels and reducing autophagy

Cited by 40 publications

References 61 publications

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

Hyperoside Attenuate Inflammation in HT22 Cells via Upregulating SIRT1 to Activities Wnt/β-Catenin and Sonic Hedgehog Pathways

Hyperoside promotes pollen tube growth by regulating the depolymerization effect of actin-depolymerizing factor 1 on microfilaments in okra

The Role of Microglia in the Development of Neurodegenerative Diseases

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