Ellagic acid promotes Aβ42 fibrillization and inhibits Aβ42-induced neurotoxicity

Feng, Ying; Yang, Sherry; Du, Xueting; Zhang, Xi; Sun, Xiaoxia; Zhao, Min; Sun, Guoxiang; Liu, Rui‐tian

doi:10.1016/j.bbrc.2009.10.130

Cited by 100 publications

(66 citation statements)

References 37 publications

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“…The mechanism of augmentation of aggregation by BA is not entirely a new observation as previously, compounds such as methylene blue and ellagic acid have also been reported to promote rapid Aβ42 fibril formation and inhibit neurotoxicity. 25,31 However, the rapid fibrillation induced by BA as reported here, which comes at the expense of toxic soluble oligomers, seems to be exclusive to the fibril formation "onpathway". The data presented in this report suggest that (a) BA is extremely potent in promoting rapid fibril formation along the "on-pathway", and (b) BA is incapable of interacting with Figure 6.…”

Section: ■ Discussionmentioning

confidence: 60%

The Natural Product Betulinic Acid Rapidly Promotes Amyloid-β Fibril Formation at the Expense of Soluble Oligomers

Planchard

Samel

Kumar

et al. 2012

ACS Chem. Neurosci.

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The biochemical hallmarks of Alzheimer's disease (AD) are the aggregates of amyloid-β (Aβ) peptide that deposit in brains of AD patients as senile plaques. The monomeric Aβ undergoes aggregation in a nucleation-dependent manner to form insoluble fibrils. Emerging evidence suggests that the low-molecular-weight aggregates called "soluble oligomers" are the primary neurotoxic agents as opposed to the fibrils. Needless to say, developing Aβ aggregation inhibitors is imperative for a meaningful progress toward AD therapy. In this report, we have explored the in vitro interactions between a natural product called betulinic acid (BA) and Aβ42 peptide. BA has found its therapeutic use in several human pathologies including cancer, HIV-related AIDS, and nervous system disorders. The results from this study indicate that BA rapidly promotes the formation of Aβ42 fibrils and, in doing so, partly circumvents the formation of potentially neurotoxic soluble oligomers. Furthermore, the promotion of fibrils by BA seems to be specific for the fibril formation "on-pathway", and it fails to interact with aggregates that are formed outside this obligatory pathway. The unique ability of BA to promote fibrils at the expense of oligomers along with its well-known pharmacological properties make BA a potential therapeutic agent for AD.

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Section: ■ Discussionmentioning

confidence: 60%

The Natural Product Betulinic Acid Rapidly Promotes Amyloid-β Fibril Formation at the Expense of Soluble Oligomers

Planchard

Samel

Kumar

et al. 2012

ACS Chem. Neurosci.

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“…17, 18 Furthermore, oxidative stress induces the accumulation of amyloid-β peptide (Aβ) causing neurotoxicity depending on amyloidogenic process of β-amyloid precursor protein. 19 It was reported that many natural phenolics are active on Alzheimer's disease as in the examples of salvianolic acid B, 20 ellagic acid, 21 curcumin, 22 flavanone, 23 rutin, and galangin.…”

Section: Resultsmentioning

confidence: 99%

HPLC analysis of Phenolic Substances and Anti-Alzheimer's Activity of KoreanQuercusSpecies

et al. 2016

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− This study aimed to establish the quantitative method to analyze the content of peroxynitrite-scavengers belonging to polyphenols in six Korean Quercus species (Quercus mongolica, Q. dentata, Q. acutissima, Q. alienta, Q. serrata, and Q. variabilis) by HPLC. The twelve peroxynitrite-scavengers, flavanols (catechins: (+)-catechin, (−)-epicatechin, and (−)-epigallocatechin), flavonols (kaempferol and quercetin), flavonol glycosides (astragalin, quercitrin, and isoquercitrin), flavonol acylated glycosides (astragalin 6''-gallate and isoquercitrin 6''-gallate), gallic acid and its dimer (ellagic acid) were analyzed by HPLC. Further, anti-Alzheimer's activity was assayed in a passive avoidance testusing mice by measuring the retention latency (sec), the concentration of acetylcholine (ACh), and acetylcholinesterase (AChE) activity. Simultaneous analysis of the extracts of the six Quercus leaves was achieved on a Capcell C18 column (5 µm, 250 mm × 4.6 mm i.d.) with a gradient elution of 0.05% HAc and 0.05% HAc in CH 3 CN. In the extract of Q. mongolica leaves, the content of gallic acid (32.53 mg/g), (+)-catechin (28.78 mg/g), (−)-epicatehin (22.03 mg/g), astragalin 6''-gallate (20.94 mg/g), and isoquercitrin 6''-gallate (44.11 mg/g) and peroxynitrite-scavenging activity (IC 50 , 0.831 µg/ml) were high. This extract delayed the retention latency and inhibited acetylcholinesterase activity in scopolamine-induced memory impairment of mice, suggesting that it has anti-Alzheimer's activity.

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“…EA prevented Aβ neurotoxicity by promoting Aβ aggregation into fibrils with significant oligomer loss. Thus EA could significantly reduce Aβ42-induced neurotoxicity toward SH-SY5Y cells [67] . Walnuts (Juglans regia L.) are an excellent source of α-linolenic acid (plant-based omega-3 fatty acid) and have a high content of antioxidants such as flavonoids, phenolic acid (ellagic acid), melatonin, gamma tocopherol and selenium.…”

Section: Coagulantactivitymentioning

confidence: 91%

“…Neuropathological hallmarks of AD are accumulation of extracellular ''senile plaques" containing amyloid β-peptide (Aβ) fibrils and intracellular ''neurofibrillary tangles" containing hyperphosphorylated tau protein [67] . Neurologicalevents that contribute to AD progression include amyloid-beta (Aβ) aggregation, acetylcholine depletion, and oxidative stress [68] .…”

Section: Ellagic Acid and Amyloid Beta (Aβ) Peptidementioning

confidence: 99%

Polyphenol Ellagic Acid-Targeting To Brain: A Hidden Treasure

Mehan¹,

Kaur²,

Parveen³

et al. 2015

International Journal of Neurology Research

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Alzheimer's disease is a severe neurodegenerative disorder that gradually results in loss of memory and impairment of cognitive functions in the elderly.Thedeposition of amyloid plaques is the primary event that leads to an oxidative and inflammatory reactions, neurofibrillary tangle formation, and ultimately neuronal death. The most prominent losses occur with cholinergic neurons that plays an important role in the formation of memory and cognitive functions. Insulin receptor numbers also altered, thusglucosemetabolism is defected in AD. Polyphenol ellagic acid (EA) possesses antioxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardioprotection activities.Activities of EA that are linked with protection of neuronal abnormalities like anti-depressant, antianxiety, anti-nociception. Ellagic acid inhibits β-secretase enzymatic activities, thus prevents the main pathologic hallmark of AD. There are varieties of herbal extracts and phytochemicals formulations extensively used to provide symptomatic relief to AD patients. Together these results our hypothesis that EA may prevent the neuronal dysfunctions as well as further work is also required to examine the pharmacological properties of EA in the protection of specially neurodegenerative disorder like AD. Here, we discuss how we can use the knowledge to improve treatment strategies of EA in AD and to explore the various signaling pathways involved in the progression of neuronal death.

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Ellagic acid promotes Aβ42 fibrillization and inhibits Aβ42-induced neurotoxicity

Cited by 100 publications

References 37 publications

The Natural Product Betulinic Acid Rapidly Promotes Amyloid-β Fibril Formation at the Expense of Soluble Oligomers

The Natural Product Betulinic Acid Rapidly Promotes Amyloid-β Fibril Formation at the Expense of Soluble Oligomers

HPLC analysis of Phenolic Substances and Anti-Alzheimer's Activity of KoreanQuercusSpecies

Polyphenol Ellagic Acid-Targeting To Brain: A Hidden Treasure

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