Natural β-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus

Ruonan Ning, Yun Lei, Shuangzhu Liu, Huan Wang, Rujun Zhang, Wei Wang, Yingdong Zhu, Haiyan Zhang, Weimin Zhao

Research output: Contribution to journalArticle

Abstract

Alzheimers disease (AD) is an irreversible, multifaceted, and progressive neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs has been primarily based on the cholinergic deficiency hypothesis and/or the β-amyloid (Aβ) cascade hypothesis. In this study, we report the identification of 16 new and 38 known β-dihydroagarofuran-type sesquiterpenoids from Celastrus flagellaris and Celastrus angulatus. The β-dihydroagarofuran-type sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced prolonged escape latency and increased number of errors compared with the control group. At 10 μM, 21 of the 62 tested β-dihydroagarofuran-type sesquiterpenoids rescued Aβ25-35-induced SH-SY5Y cells from viability reduction, which increased the cell viability from 64.6% for the model to more than 74.0%. The majority of the β-dihydroagarofuran-type sesquiterpenoids with ester groups exhibited stronger activity than those with free hydroxy groups or without substituents at the same positions. These results identified a new chemical skeleton as drug lead for the investigation of novel therapeutic agents against AD.

Original languageEnglish (US)
Pages (from-to)2175-2186
Number of pages12
JournalJournal of Natural Products
Volume78
Issue number9
DOIs
StatePublished - Sep 25 2015
Externally publishedYes

Fingerprint

Celastrus
Neuroprotective Agents
Medicinal Plants
Cognition
Alzheimer Disease
Cell Survival
Scopolamine Hydrobromide
Amyloid
Skeleton
Neurodegenerative Diseases
Pharmaceutical Preparations
Cholinergic Agents
Esters
Cells
Control Groups
dihydroagarofuran

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Natural β-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus. / Ning, Ruonan; Lei, Yun; Liu, Shuangzhu; Wang, Huan; Zhang, Rujun; Wang, Wei; Zhu, Yingdong; Zhang, Haiyan; Zhao, Weimin.

In: Journal of Natural Products, Vol. 78, No. 9, 25.09.2015, p. 2175-2186.

Research output: Contribution to journalArticle

Ning, Ruonan ; Lei, Yun ; Liu, Shuangzhu ; Wang, Huan ; Zhang, Rujun ; Wang, Wei ; Zhu, Yingdong ; Zhang, Haiyan ; Zhao, Weimin. / Natural β-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus. In: Journal of Natural Products. 2015 ; Vol. 78, No. 9. pp. 2175-2186.
@article{1c63bed36f854a41958f191990a0de45,
title = "Natural β-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus",
abstract = "Alzheimers disease (AD) is an irreversible, multifaceted, and progressive neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs has been primarily based on the cholinergic deficiency hypothesis and/or the β-amyloid (Aβ) cascade hypothesis. In this study, we report the identification of 16 new and 38 known β-dihydroagarofuran-type sesquiterpenoids from Celastrus flagellaris and Celastrus angulatus. The β-dihydroagarofuran-type sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced prolonged escape latency and increased number of errors compared with the control group. At 10 μM, 21 of the 62 tested β-dihydroagarofuran-type sesquiterpenoids rescued Aβ25-35-induced SH-SY5Y cells from viability reduction, which increased the cell viability from 64.6{\%} for the model to more than 74.0{\%}. The majority of the β-dihydroagarofuran-type sesquiterpenoids with ester groups exhibited stronger activity than those with free hydroxy groups or without substituents at the same positions. These results identified a new chemical skeleton as drug lead for the investigation of novel therapeutic agents against AD.",
author = "Ruonan Ning and Yun Lei and Shuangzhu Liu and Huan Wang and Rujun Zhang and Wei Wang and Yingdong Zhu and Haiyan Zhang and Weimin Zhao",
year = "2015",
month = "9",
day = "25",
doi = "10.1021/acs.jnatprod.5b00234",
language = "English (US)",
volume = "78",
pages = "2175--2186",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Natural β-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus

AU - Ning, Ruonan

AU - Lei, Yun

AU - Liu, Shuangzhu

AU - Wang, Huan

AU - Zhang, Rujun

AU - Wang, Wei

AU - Zhu, Yingdong

AU - Zhang, Haiyan

AU - Zhao, Weimin

PY - 2015/9/25

Y1 - 2015/9/25

N2 - Alzheimers disease (AD) is an irreversible, multifaceted, and progressive neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs has been primarily based on the cholinergic deficiency hypothesis and/or the β-amyloid (Aβ) cascade hypothesis. In this study, we report the identification of 16 new and 38 known β-dihydroagarofuran-type sesquiterpenoids from Celastrus flagellaris and Celastrus angulatus. The β-dihydroagarofuran-type sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced prolonged escape latency and increased number of errors compared with the control group. At 10 μM, 21 of the 62 tested β-dihydroagarofuran-type sesquiterpenoids rescued Aβ25-35-induced SH-SY5Y cells from viability reduction, which increased the cell viability from 64.6% for the model to more than 74.0%. The majority of the β-dihydroagarofuran-type sesquiterpenoids with ester groups exhibited stronger activity than those with free hydroxy groups or without substituents at the same positions. These results identified a new chemical skeleton as drug lead for the investigation of novel therapeutic agents against AD.

AB - Alzheimers disease (AD) is an irreversible, multifaceted, and progressive neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs has been primarily based on the cholinergic deficiency hypothesis and/or the β-amyloid (Aβ) cascade hypothesis. In this study, we report the identification of 16 new and 38 known β-dihydroagarofuran-type sesquiterpenoids from Celastrus flagellaris and Celastrus angulatus. The β-dihydroagarofuran-type sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced prolonged escape latency and increased number of errors compared with the control group. At 10 μM, 21 of the 62 tested β-dihydroagarofuran-type sesquiterpenoids rescued Aβ25-35-induced SH-SY5Y cells from viability reduction, which increased the cell viability from 64.6% for the model to more than 74.0%. The majority of the β-dihydroagarofuran-type sesquiterpenoids with ester groups exhibited stronger activity than those with free hydroxy groups or without substituents at the same positions. These results identified a new chemical skeleton as drug lead for the investigation of novel therapeutic agents against AD.

UR - http://www.scopus.com/inward/record.url?scp=84942594556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942594556&partnerID=8YFLogxK

U2 - 10.1021/acs.jnatprod.5b00234

DO - 10.1021/acs.jnatprod.5b00234

M3 - Article

C2 - 26295746

AN - SCOPUS:84942594556

VL - 78

SP - 2175

EP - 2186

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 9

ER -