Icariside II protects against cerebral ischemia–reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation

Deng, Yuanyuan; Xiong, Deqing; Yin, Caixia; Liu, Bo; Shi, Jingshan; Gong, Qihai

doi:10.1016/j.neuint.2016.02.015

Cited by 49 publications

(41 citation statements)

References 37 publications

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“…One of its bioactive flavonoid compounds, ICS II, shows good CNS penetration and robust biological activities. ICS II protect against cerebral ischemia reperfusion injury in rats via an integrated mechanism of nuclear factor-κB inhibition and peroxisome proliferator activated receptor up-regulation (Deng et al, 2016). Similarly, ICS II alleviates hippocampal injury in a gerbil model of ischemia-reperfusion (Yan et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

et al. 2017

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Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer’s disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effectively ameliorated cognitive function deficits, but also inhibited neuronal degeneration and reduced the formation of plaque burden. ICS II significantly suppressed Aβ production via promoting non-amyloidogenic APP cleavage process by up-regulating a disintegrin and metalloproteinase domain 10 (ADAM10) expression, inhibited amyloidogenic APP processing pathway by down-regulating amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1) expression in APP/PS1 transgenic mice. Meanwhile, ICS II attenuated peroxisome proliferator-activated receptor-γ (PPARγ) degradation as well as inhibition of eukaryotic initiation factor α phosphorylation (p-eIF2α) and PKR endoplasmic reticulum regulating kinase phosphorylation (p-PERK). Moreover, phosphodiesterase type 5 inhibitors (PDE5-Is) have recently emerged as a possible therapeutic target for cognitive enhancement via inhibiting Aβ levels, and we also found that ICS II markedly decreased phosphodiesterase-5A (PDE5A) expression. In conclusion, the present study demonstrates that ICS II could attenuate spatial learning and memory impairments in APP/PS1 transgenic mice. This protection appears to be due to the increased ADAM10 expression and decreased expression of both APP and BACE1, resulting in inhibition of Aβ production in the hippocampus and cortex. Inhibition of PPARγ degradation and PERK/eIF2α phosphorylation are involved in the course, therefore suggesting that ICS II might be a promising potential compound for the treatment of AD.

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Section: Introductionmentioning

confidence: 99%

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

et al. 2017

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“…Because it possesses a polyphenolic structure similar to resveratrol, icariin may activate SIRT1 through similar mechanisms (Canto et al ., ; Park et al ., ; Verdin, ). Recent studies have shown that icariin and its metabolites protect against cerebral I/R injury in rats via NF‐κB inhibition and PPAR activation (Deng et al ., ; Xiong et al ., ). In addition, cardioprotective effects of icariin have also been described, such as attenuating the damage induced by I/R in rats through activating the PI3K/Akt pathway (Ke et al ., ; Meng et al ., ; Zhai et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1‐dependent mitochondrial oxidative damage

Feng

et al. 2018

British J Pharmacology

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“…The herb is proven to have remarkable therapeutic activities to promote osteoblastic proliferation, ameliorate streptozotocininduced diabetic nephropathy in diabetic rats, alleviate ischemia-reperfusion-induced hippocampal injury in gerbils, and inhibit the growth of the various cancer cell lines (22). ICA II, an active flavonoid glycoside derived from Herba Epimedii, also has multiple effects on various diseases, especially some notable protective effects on cognitive deficits and cerebral ischemia-reperfusion injury (9). Although the precise mechanism involved still needs further study, ICA II might be a potential candidate to treat SAH related chronic hydrocephalus by inhibiting the TGF-β1/Smad/CTGF pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging data on secondary brain ischemia after SAH and some common signaling pathways and therapeutic targets relating ischemia/reperfusion injury and hydrocephalus may offer a novel therapeutic target. It is reported that ICA II protects against cerebral ischemia/reperfusion injury and alleviates the microcirculatory disturbance and neuronal injury via up-regulation of PPARα and PPARγ and inhibition of NF-κB activation (9). In addition to that, ICA II has been found to induce apoptosis in various human cancer cell lines of different origin by targeting multiple signaling pathways including STAT3, PI3K/AKT, MAPK/ERK, COX-2/PGE2 and β-Catenin which are frequently deregulated in cancers (23).…”

Section: Discussionmentioning

confidence: 99%

“…Icariin (C33H40O15, 676.67 Da) and its metabolite IcarisideⅡ(ICA II, C27H32O10, 514.54 Da) are the two main bioactive products present in this herb, which have been demonstrated to possess broad therapeutic capabilities, especially anti-osteoporosis, antioxidative stress, anti-cancer and neuroprotective effects. In recent years, some preclinical studies have demonstrated neuroprotective effects of ICA II in Alzheimer's _________________________________________ disease (AD) and ischemic brain injury; it enhanced neurogenesis and promoted memory (9,10). It can be expected that ICA II may have some protective role in SAH related chronic hydrocephalus for the person who suffers from chronic hydrocephalus will usually have similar cognitive deficits as ischemic brain injury patients.…”

Section: Introductionmentioning

confidence: 99%

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Icariside II Attenuates Chronic Hydrocephalus in an Experimental Subarachnoid Hemorrhage Rat Model

Dong¹,

Ming²,

Ye³

et al. 2018

J Pharm Pharm Sci

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Purpose To investigate the role of ICA II in subarachnoid hemorrhage (SAH)- related chronic hydrocephalus. Methods A two hemorrhage injection model of SAH was created in Sprague Dawley rats (6-8 weeks). A total of 125 rats were randomly assigned into five groups: Sham group, SAH group, SAH+ ICA II (1 mg/kg) group, SAH + ICA II (5 mg/kg) group, and SAH + ICA II (10 mg/kg) group. TGF-β1, phospho-Smad2/3, connective tissue growth factor (CTGF), and procollagen type I carboxy-terminal propeptide (PICP) were assessed via real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. Lateral ventricular index, Masson staining, and Morris water maze tests were employed to evaluate subarachnoid fibrosis, hydrocephalus, and long term neurological function following SAH. Results ICA II (1, 5, 10 mg/kg) inhibited subarachnoid fibrosis, attenuated ventriculomegaly, and effectively suppressed SAH related chronic hydrocephalus. In addition, parallel reduced expression of members of the TGF-β1/Smad/CTGF signaling pathway were observed. Importantly, ICA II may improve long term neurocognitive deficits after SAH. Conclusion ICA II might suppress fibrosis via inhibition of TGF-β1/Smad/CTGF pathway, prevent the development of SAH related chronic hydrocephalus, and improve long term neurocognitive defects following SAH.

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Icariside II protects against cerebral ischemia–reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation

Cited by 49 publications

References 37 publications

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

Icariside II Effectively Reduces Spatial Learning and Memory Impairments in Alzheimer’s Disease Model Mice Targeting Beta-Amyloid Production

Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1‐dependent mitochondrial oxidative damage

Icariside II Attenuates Chronic Hydrocephalus in an Experimental Subarachnoid Hemorrhage Rat Model

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