Update on the effect of estradiol in postmenopause women with Alzheimer’s disease: a systematic review

Lan, Yu‐Long; Zou, Shuang; Zhang, Changfu; Li, Jun; Xu, Yunhua; Li, Shao

doi:10.1007/s13760-015-0593-y

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…Because depletion of 17-β-estradiol is an established risk factor for AD in post-menopausal women [18], phytoestrogen have become interesting candidates for a possible prevention and/or treatment of AD [19]. Phytoestrogen β-Ecdysterone (β-Ecd) derived from the Achyranthes bidentata BI., which is used in folk medicine to improve memory function, has been reported to exhibit neuroprotective effects and antioxidant properties [20].…”

Section: Introductionmentioning

confidence: 99%

β-Ecdysterone protects SH-SY5Y cells against β-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways

Niu

Zhang

et al. 2018

Laboratory Investigation

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Recently, the significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to the loss of neuroprotective estrogen after menopause. Does phytoestrogen have the ability to protect against amyloid-β (Aβ) toxicity? The aim of this study was to evaluate hypothesis that β-ecdysterone (β-Ecd) protects SH-SY5Y cells from Aβ-induced apoptosis by separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal kinase (JNK). Here, we demonstrate that phytoestrogen β-Ecd inhibits Aβ-triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation. Interestingly, β-Ecd upregulates Bcl-2 expression in SH-SY5Y cells under both basal and Aβ-challenged conditions, but downregulates Bax expression only in Aβ-challenged conditions. Subsequently, Akt-dependent NF-κB activation is required for Bcl-2 upregulation, but not Bax downregulation, in response to β-Ecd, which was validated by the use of LY294002 and Bay11-7082. Notably, β-Ecd attenuates the Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and JNK activation without altering the basal ASK1 phosphorylation and JNK activation. ROS-scavenging by diphenyleneiodonium (DPI) abrogated the ability of β-Ecd to alter the activation of ASK1. Simultaneously, inhibition of JNK by SP600125 abolished β-Ecd-induced Bax downregulation in Aβ-challenged SH-SY5Y cells, whereas LY294002 failed to do so. Consequently, β-Ecd possesses neuroprotection by different and complementary pathways, which together promote a Bcl-2/Bax ratio. These data support our hypothesis and suggest that β-Ecd is a promising candidate for the treatment of AD.

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Section: Introductionmentioning

confidence: 99%

β-Ecdysterone protects SH-SY5Y cells against β-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways

Niu

Zhang

et al. 2018

Laboratory Investigation

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“…Some studies have shown that Lutein is involved in preventing cognitive decline and decreasing the risk of AD; thus, Lutein may contribute to the treatment of AD ( Kiko et al, 2012 ; Min & Min, 2014 ; Xu & Lin, 2015 ). Similarly, Vitamin A, Vitamin E, Estradiol, Menthol, Glyburide and Yohimbine are also considered useful in the prevention and treatment of AD ( Bhadania et al, 2012 ; Dysken et al, 2014 ; Lamkanfi et al, 2009 ; Lan et al, 2016 ; Mohamd et al, 2011 ; Ono & Yamada, 2012 ; Peskind et al, 1995 ; Takasaki et al, 2011 ). Therefore, compounds with structures similar to the existing drugs may also have anti-AD function by interacting with similar target proteins.…”

Section: Resultsmentioning

confidence: 99%

A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants

Chen

Wang

et al. 2018

PeerJ

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BackgroundAlzheimer’ disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs.MethodsWe used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins. TCM compounds in the top 0.5% of binding affinity scores for each target protein were selected as our research objects. Structural similarities between existing drugs from DrugBank database and selected TCM compounds as well as the druggability of our candidate compounds were studied. Finally, we searched the CNKI database to obtain studies on anti-AD Chinese plants from 2007 to 2017, and only clinical studies were included.ResultsA total of 1,476 compounds (top 0.5%) were selected as drug candidates. Most of these compounds are abundantly found in plants used for treating AD in China, especially the plants from two genera Panax and Morus. We classified the compounds by single target and multiple targets and analyzed the interactions between target proteins and compounds. Analysis of structural similarity revealed that 17 candidate anti-AD compounds were structurally identical to 14 existing approved drugs. Most of them have been reported to have a positive effect in AD. After filtering for compound druggability, we identified 11 anti-AD compounds with favorable properties, seven of which are found in anti-AD Chinese plants. Of 11 anti-AD compounds, four compounds 5,862, 5,863, 5,868, 5,869 have anti-inflammatory activity. The compound 28,814 mainly has immunoregulatory activity. The other six compounds have not yet been reported for any biology activity at present.DiscussionNatural compounds from TCM provide a broad prospect for the screening of anti-AD drugs. In this work, we established networks to systematically study the connections among natural compounds, approved drugs, TCM plants and AD target proteins with the goal of identifying promising drug candidates. We hope that our study will facilitate in-depth research for the treatment of AD in Chinese medicine.

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“…A structural comparison between all existing approved drugs recorded in the DrugBank and Yohimbine are also considered useful in the prevention and treatment of AD (Bhadania et al 2012;Dysken et al 2014;Lamkanfi et al 2009;Lan et al 2016;Mohamd et al 2011;Ono & Yamada 2012;Peskind et al 1995;Takasaki et al 2011). Therefore, compounds with structures similar to the existing drugs may also have anti-AD function by interacting with similar target proteins.…”

Section: Similarities Between Candidate Compounds and Existing Drugsmentioning

confidence: 99%

Peer Review #1 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.1)"

Silva¹

2018

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Background Alzheimer' disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs. Methods We used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins. TCM compounds in the top 0.5% of binding affinity scores for each target protein were selected as our research objects. Structural similarities between existing drugs from DrugBank database and selected TCM compounds as well as the druggability of our candidate compounds were studied. Finally, we searched the CNKI database to obtain studies on anti-AD Chinese plants from 2007 to 2017, and only clinical studies were included. Results A total of 1476 compounds (top 0.5%) were selected as drug candidates. Most of these compounds are abundantly found in plants used for treating AD in China, especially the plants from two genera Panax and Morus. We classified the compounds by single target and multiple targets and analyzed the interactions between target proteins and compounds. Analysis of structural similarity revealed that 17 candidate anti-AD compounds were structurally identical to 14 existing approved drugs. Most of them have been reported to have a positive effect in AD. After filtering for compound druggability, we identified 11 anti-AD compounds with favorable properties, 7 of which are found in anti-AD Chinese plants. Of 11 anti-AD compounds, 4 compounds 5862, 5863, 5868, 5869 have antiinflammatory activity. The compound 28814 mainly has immunoregulatory activity. The other 6 compounds have not yet been reported for any biology activity at present. Discussion Natural compounds from TCM provide a broad prospect for the screening of anti-AD drugs. In this work, we established networks to systematically study the connections among natural compounds, approved drugs, TCM plants and AD target proteins with the goal of identifying promising drug candidates. We hope that our study will facilitate in-depth research for the treatment of AD in Chinese medicine.

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Update on the effect of estradiol in postmenopause women with Alzheimer’s disease: a systematic review

Cited by 7 publications

References 45 publications

β-Ecdysterone protects SH-SY5Y cells against β-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways

β-Ecdysterone protects SH-SY5Y cells against β-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways

A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants

Peer Review #1 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.1)"

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