Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments

Xiaohang Li; Jin Cui; Yang Yu; Wei Li; Yujun Hou; Xin Wang; Dapeng Qin; Cun Zhao; Xinsheng Yao; Jian Zhao; Gang Pei

doi:10.1371/journal.pone.0151147

Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments

PLoS One. 2016 Mar 8;11(3):e0151147. doi: 10.1371/journal.pone.0151147. eCollection 2016.

Authors

Xiaohang Li^{1

2}, Jin Cui^{1

2}, Yang Yu³, Wei Li^{1

2}, Yujun Hou¹, Xin Wang^{1

2}, Dapeng Qin³, Cun Zhao^{1

2}, Xinsheng Yao³, Jian Zhao^{1

4}, Gang Pei^{1

5}

Affiliations

¹ State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
² Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
³ Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
⁴ Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
⁵ School of Life Science and Technology, Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China.

Abstract

Decline of cognitive function is the hallmark of Alzheimer's disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / metabolism
Alzheimer Disease / physiopathology
Amyloid Precursor Protein Secretases / metabolism
Amyloid beta-Peptides / biosynthesis*
Animals
Aspartic Acid Endopeptidases / metabolism
Cell Line
Cognition Disorders / drug therapy
Cognition Disorders / metabolism*
Disease Models, Animal
Drugs, Chinese Herbal / pharmacology*
Enzyme Activation / drug effects
Humans
Medicine, Chinese Traditional*
Mice
Mice, Transgenic
Nootropic Agents / pharmacology*
Proteolysis / drug effects
Saponins / pharmacology*
Substrate Specificity
Triterpenes / pharmacology*

Substances

Amyloid beta-Peptides
Drugs, Chinese Herbal
Nootropic Agents
Saponins
Triterpenes
onjisaponin B
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Bace1 protein, mouse

Grants and funding

This research was supported by the National Natural Science Foundation of China (31371419), Ministry of Health (2012BAI10B03) and Shanghai Municipal Commission for Science and Technology (13401900600, 14DZ1900402).