Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats

Song, Xiu-Yun; Hu, Jin‐Feng; Chu, Shifeng; Zhang, Zhao; Xu, Shengwen; Yuan, Yu‐He; Han, Ning; Liu, Yan; Niu, Fei; He, Xin; Chen, Nai‐Hong

doi:10.1016/j.ejphar.2013.03.051

Cited by 93 publications

(50 citation statements)

References 52 publications

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“…In the present study, unilateral icv injection of OKA induced spatial memory impairments, which is consistent with previous studies [5] . IMM-H004 has been shown to ameliorate spatial learning performance in global ischemia [9] , and to inhibit Aβ-induced neuronal apoptosis [6,9] .…”

Section: Discussionsupporting

confidence: 82%

“…Furthermore, donepezil could attenuate Aβ-associated mitochondrial dysfunction and reduce mitochondrial Aβ accumulation in vivo and in vitro, which might differ from its previously reported effect on AChE [28] . Our previous study [5] indicated that donepezil could ameliorate OKA-induced hyperphosphorylation of tau and Aβ accumulation. Therefore, donepezil improved OKA-induced neurotoxicity possibly through PP2A activation or by improving cholinergic functioning.…”

Section: Discussionmentioning

confidence: 99%

“…Memory impairments have been induced in animal models through microinjection of OKA into the brain [5,13] . In the present study, unilateral icv injection of OKA induced spatial memory impairments, which is consistent with previous studies [5] .…”

Section: Discussionmentioning

confidence: 99%

“…The groups and treatment conditions are detailed in Table 1. The effective doses of OKA, IMM-H004 and donepezil were determined according to our previous studies [5,9] . The total duration of the experimental period was 26 days (Figure 2A).…”

Section: Experimental Designmentioning

confidence: 99%

“…Infusion of OKA into the rat brain causes severe memory impairments that are accompanied by remarkable neuropathological changes, including hippocampal neurodegeneration, a paired helical filament-like phosphorylation of tau, Aβ accumulation and neuronal apoptosis [2][3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

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A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

et al. 2016

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Aim: A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) has shown antiapoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms. Methods: SD rats were administered IMM-H004 (8 mg·kg -1 ·d -1 , ig) or donepezil (positive control, 1 mg·kg -1 ·d -1 , ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and β-amyloid (Aβ) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. Results: OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aβ protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil. Conclusion: Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aβ pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

et al. 2016

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Preclinical Models of Alzheimer's Disease: Relevance and Translational Validity

Mullane

Williams

2019

CP Pharmacology

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The only drugs currently approved for the treatment of Alzheimer's Disease (AD) are four acetylcholinesterase inhibitors and the NMDA antagonist memantine. Apart from these drugs, which have minimal to no clinical benefit, the 40‐year search for effective therapeutics to treat AD has resulted in a clinical failure rate of 100% not only for compounds that prevent brain amyloid deposition or remove existing amyloid plaques but also those acting by a variety of other putative disease‐associated mechanisms. This indicates that the preclinical data generated from current AD targets to support the selection, optimization, and translation of new chemical entities (NCEs) and biologics to clinical trials is seriously compromised. While many of these failures reflect flawed hypotheses or a lack of adequate characterization of the preclinical pharmacodynamic and pharmacokinetic (PD/PK) properties of lead NCEs—including their bioavailability and toxicity—the conceptualization, validation, and interrogation of the current animal models of AD represent key limitations. The overwhelming majority of these AD models are transgenic, based on aspects of the amyloid hypothesis and the genetics of the familial form of the disease. As a result, these generally lack construct and predictive validity for the sporadic form of the human disease. The 170 or so transgenic models, perhaps the largest number ever focused on a single disease, use rodents, mainly mice, and in addition to amyloid also address aspects of tau causality with more complex multigene models including other presumed causative factors together with amyloid. This overview discusses the current animal models of AD in the context of both the controversies surrounding the causative role of amyloid in the disease and the need to develop validated models of cognitive function/dysfunction that more appropriately reflect the phenotype(s) of human aged‐related dementias. © 2019 by John Wiley & Sons, Inc.

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Comparison of microwave‐assisted and heat reflux extraction techniques for the extraction of ten major compounds from Zibu Piyin Recipe using ultra high performance liquid chromatography with tandem mass spectrometry

Zhan

Zhang

2016

J of Separation Science

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Microwave-assisted extraction and efficient ultra-high performance liquid chromatography with triple quadrupole mass spectrometry were previously used to quickly extract and simultaneously quantify ginsenoside Rf, Ro, and Rd, 20(S)-ginsenoside-Rg2 , 20(R)-ginsenoside-Rg2 , tanshinone IIA, cryptotanshinone, dihydrotanshinone I, lithospermic acid, and osthole from Zibu Piyin Recipe. We here showed that heat reflux extraction provides higher extraction efficiency of these target compounds but is more time consuming. Chromatographic separation was achieved on an Agilent ZORBAX RRHD Eclipse Plus C18 column with a gradient mobile phase consisting of water/0.5% formic acid and acetonitrile at a flow rate of 0.2 mL/min, and detection was performed by positive and negative ion multiple-reaction monitoring mode. All analytes showed good linearity (r, 0.9989-0.9999) within the test range, with a limit of detection of 0.002-0.180 μg/mL. The overall intra- and interday variations of the ten compounds were ≤2.9%, and the accuracy was evaluated using a recovery test at three concentrations and was in the range 97.61-103.18% (RSD ≤ 4.25%). The analytical results showed remarkable differences in the concentrations of the ten compounds extracted from Zibu Piyin Recipe by microwave-assisted extraction and heat reflux extraction. These findings provide important information for determining the quality of Zibu Piyin Recipe.

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Ginsenoside Rg1 attenuates okadaic acid induced spatial memory impairment by the GSK3β/tau signaling pathway and the Aβ formation prevention in rats

Cited by 93 publications

References 52 publications

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

Preclinical Models of Alzheimer's Disease: Relevance and Translational Validity

Comparison of microwave‐assisted and heat reflux extraction techniques for the extraction of ten major compounds from Zibu Piyin Recipe using ultra high performance liquid chromatography with tandem mass spectrometry

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