A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent pathways

Tang, Genyun; Dong, Xiao; Huang, Xiang; Liu, H.; Wang, Yuhong; Ye, Wen‐Cai; Shi, Lei

doi:10.1016/j.neuroscience.2015.07.019

Cited by 39 publications

(37 citation statements)

References 48 publications

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“…AO-1 has been proven to be able of crossing the blood brain barrier and promote differentiation of newborn neurons in the dentate gyrus. 23) Further studies using AD animal models will be carried out to test the effects of AO-1 administration. Moreover, curcumin and its derivatives, a class of well-known anti-Aβ compounds that are structurally close to AO-1, directly bind to Aβ and inhibits its oligomerization.…”

Section: Discussionmentioning

confidence: 99%

“…1) and 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4E-hepten-3-one (AO-2), promotes differentiation and neurite outgrowth in both Neuro-2a cells and cultured hippocampal neurons through activation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) pathways, and AO-1 accelerates differentiation of newborn neurons in vivo. 23) Both diarylheptanoids were isolated from the rhizomes of Alpinia officinarum, a Zingiberaceae plant long used as a traditional Chinese medicine and a popular spice. Given the beneficial effects of AO-1 on neuronal differentiation in vitro and in vivo, this study aims at further interrogating whether this compound protects Aβ-injured neurons to retain their viability and differentiation abilities.…”

Section: -3)mentioning

confidence: 99%

“…Our previous study suggested that AO-1-promoted neurite growth is dependent on activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-ERK and PI3K-Akt signaling pathways. 23) We then asked whether AO-1 regulates the same pathways during neuroprotection. Interestingly, blockade of MEK activity by U0126 did not inhibit AO-1's effect on downregulating caspase-3 cleavage (Figs.…”

Section: Ao-1 Alleviated Dendritic Impairments Induced By Aβ42mentioning

confidence: 99%

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7-(4-Hydroxyphenyl)-1-phenyl-4E-hepten-3-one, a Diarylheptanoid from Alpinia officinarum, Protects Neurons against Amyloid-β Induced Toxicity

Huang

Tang

Liao

et al. 2016

Biological & Pharmaceutical Bulletin

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Amyloid-β (Aβ) is one of the major causative agents of Alzheimer's disease (AD), the most common neurodegenerative disorder characterized by progressive cognitive impairment. While effective drugs for AD are currently limited, identifying anti-Aβ compounds from natural products has been shown as a promising strategy which may lead to breakthroughs for new drug candidate discovery. We have previously reported that 7-(4-hydroxyphenyl)-1-phenyl-4E-hepten-3-one (AO-1), a diarylheptanoid extracted from the plant Alpinia officinarum, has strong effects on neuronal differentiation and neurite outgrowth in vitro and in vivo. The present study further uncovers that AO-1 exerts neuroprotective effects against the neurotoxicity caused by Aβ. Under the damage of Aβ oligomers, the major pathological forms of Aβ, dendrites of neurons become atrophic and simplified, but such impairments were substantially alleviated by AO-1 treatment. Moreover, AO-1 reduced apoptotic levels and oxidative stress triggered by Aβ. Further analysis showed that the anticaspase and dendrite protective effects of AO-1 were dependent on activation of phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathways. These findings collectively identify AO-1 as a beneficial compound to ameliorate the deleterious effects of Aβ on dendrite integrity and cell survival, and may provide new insights on drug discovery of AD.Key words Alzheimer's disease (AD); amyloid-β (Aβ); dendrite; mammalian target of rapamycin (mTOR); neuroprotection; phosphatidylinositol 3-kinase (PI3K) Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the elderly which is characterized by progressive cognitive decline and movement dysfunction. Being a disease with extremely complex etiology, the accumulation of amyloid-β (Aβ) peptides is believed as a main pathogenic event that directly causes neurodegeneration. 1-3)Aβ peptides, which are normally constituted by 40-42 amino acids, are released by the aberrant cleavage of amyloid precursor protein (APP) and deposit at synapses. Aβ peptides are the major component of the senile plaques observed in AD brain. Moreover, soluble oligomers formed by aggregation of monomeric Aβ42 (1-42 a.a.) peptides are the most pathogenic forms during early progression of AD. The damaging effects of Aβ42 includes synapse loss, neurite dystrophy and dendritic simplification.4,5) Thus, one of the current efforts for drug development against AD is to generate platforms that aim at antagonizing the devastating effects of Aβ oligomers. Such approaches have been proven promising for therapeutic design and drug discovery of AD. [6][7][8] A variety of compounds derived from natural sources have been identified effective for counteracting Aβ-induced neurotoxicity.9,10) Such anti-Aβ activities could be achieved through several ways. For instance, Aβ production or aggregation is prevented, or Aβ clearance is accelerated. Moreover, Aβ-induced signaling pathways could be blocked or downregulated. A great number of natural compou...

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Section: Discussionmentioning

confidence: 99%

Section: -3)mentioning

confidence: 99%

Section: Ao-1 Alleviated Dendritic Impairments Induced By Aβ42mentioning

confidence: 99%

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7-(4-Hydroxyphenyl)-1-phenyl-4E-hepten-3-one, a Diarylheptanoid from Alpinia officinarum, Protects Neurons against Amyloid-β Induced Toxicity

Huang

Tang

Liao

et al. 2016

Biological & Pharmaceutical Bulletin

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“…The biological activity of plants may be due to phenolic compounds that are known to confer antioxidant, antitumorgenic, antinflammatory, or other favourable activities [3][4][5]. One of the many potential pharmaceutical uses of phenolic compounds is the treatment and prevention of neural diseases [6][7][8]. Phenolic compounds that can cross the bloodbrain barrier can indicate neuroprotective functions and clinical potential of the central nervous system which has a limited ability to repair and regenerate [3,9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Two major groups of neuroprotective phytochemicals are diarylheptanoids, such as curcumin, and flavonoids, such as quercetin ( Fig. 1) [6,11]. Flavonoids and diarylheptanoids are neuroprotective, are able to protect neurons from damage, particularly through free radical scavenging activity, modulation of neuroplasticity resulting in an increase in cognitive, behavioral and/or emotional function, e.g., improving memory [11,6,12].…”

Section: Introductionmentioning

confidence: 99%

Flavonoids and Diarylheptanoids: Neuroprotective Activities of Phytochemicals

Parasram

2017

IJPPE

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Abstract. Plants are often used as sources of lead compounds with phenolic compounds frequently attributed to physiological effects. Flavonoids and diarylheptanoids are important groups of phenolic compounds that impart antioxidant, antitumorgenic, antinflammatory, and neuroprotective effects. These neuroprotective effects can be harnessed to develop treatments for neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Recent discoveries have characterized new neuroprotective compounds and/or sources and tested treatments on cell lines and model animals to improve treatments for future persons with neurodegenerative disorders.

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Arhgef1 negatively regulates neurite outgrowth through activation of RhoA signaling pathways

Xiang

Zhuang

et al. 2016

FEBS Letters

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Neurite outgrowth is essential for the establishment of functional neuronal connections during brain development. This study identifies that Arhgef1 is predominantly expressed in early neuronal developmental stages and negatively regulates neurite outgrowth. Knockdown of Arhgef1 in either Neuro‐2a cells or primary cortical neurons leads to excess growth of neurites, whereas overexpression of Arhgef1 prominently restricts neurite formation. Arhgef1 strongly activates RhoA activity while concomitantly inhibits Rac1 and Cdc42 activities. Pharmacological blockade of RhoA activity restores normal neurite outgrowth in Arhgef1‐overexpressed neurons. Importantly, Arhgef1 promotes F‐actin polymerization in neurons, probably through inhibiting the activity of the actin‐depolymerizing factor cofilin. Collectively, these findings reveal that Arhgef1 functions as a negative regulator of neurite outgrowth through regulating RhoA‐cofilin pathway and actin dynamics.

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A natural diarylheptanoid promotes neuronal differentiation via activating ERK and PI3K-Akt dependent pathways

Cited by 39 publications

References 48 publications

7-(4-Hydroxyphenyl)-1-phenyl-4<i>E</i>-hepten-3-one, a Diarylheptanoid from <i>Alpinia officinarum</i>, Protects Neurons against Amyloid-β Induced Toxicity

7-(4-Hydroxyphenyl)-1-phenyl-4<i>E</i>-hepten-3-one, a Diarylheptanoid from <i>Alpinia officinarum</i>, Protects Neurons against Amyloid-β Induced Toxicity

Flavonoids and Diarylheptanoids: Neuroprotective Activities of Phytochemicals

Arhgef1 negatively regulates neurite outgrowth through activation of RhoA signaling pathways

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