A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques. Recently we have identified a novel function of a patented formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese...

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Main Authors: Siva Sundara Kumar Durairajan, Ashok Iyaswamy, Sravan Gopalakrishna Shetty, Ananth Kumar Kammella, Sandeep Malampati, Wenbin Shang, Chuanbin Yang, Juxian Song, Sookja Chung, Jiandong Huang, Kaliappan Ilango, Quan-Bin Han, Min Li
Format: Article
Language:English
Published: Nature Publishing Group 2017-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-06217-9
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spelling doaj-62e10df4806746c0afad06ad28e8e2022020-12-08T01:36:18ZengNature Publishing GroupScientific Reports2045-23222017-07-017111310.1038/s41598-017-06217-9A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s diseaseSiva Sundara Kumar Durairajan0Ashok Iyaswamy1Sravan Gopalakrishna Shetty2Ananth Kumar Kammella3Sandeep Malampati4Wenbin Shang5Chuanbin Yang6Juxian Song7Sookja Chung8Jiandong Huang9Kaliappan Ilango10Quan-Bin Han11Min Li12Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityDepartment of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong KongPhytochemistry and Analysis laboratory, Interdisciplinary Institute of Indian System of Medicine, SRM UniversityNatural Products Chemistry & Analysis Laboratory, School of Chinese Medicine, Hong Kong Baptist UniversityNeuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist UniversityAbstract Alzheimer’s disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques. Recently we have identified a novel function of a patented formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese herbal medicine, in treating AD in in vitro studies (US patent No. 9,375,457). HLJDT-M is a formulation composed of Rhizoma Coptitis, Cortex Phellodendri and Fructus Gardeniae without Radix Scutellariae. Here, we assessed the efficacy of HLJDT-M on a triple transgenic mouse model of AD (3XTg-AD). Oral administration of HLJDT-M ameliorated the cognitive dysfunction of 3XTg-AD mice and lessened the plaque burden. In addition, biochemical assays revealed a significant decrease in levels of detergent-soluble and acid-soluble Aβ via decreasing the levels of full length amyloid-β precursor protein (FL-APP) and C-terminal fragments of APP (CTFs) in brain lysates of HLJDT-M-treated mice. HLJDT-M treatment also significantly reduced the levels of FL-APP and CTFs in N2a/SweAPP cells. In contrast, treatment using the classical formula HLJDT did not reduce the memory impairment of 3XTg-AD mice and, rather, increased the Aβ/Fl-APP/CTFs in both animal and cell culture studies. Altogether, our study indicates that HLJDT-M is a promising herbal formulation to prevent and/or cure AD.https://doi.org/10.1038/s41598-017-06217-9
collection DOAJ
language English
format Article
sources DOAJ
author Siva Sundara Kumar Durairajan
Ashok Iyaswamy
Sravan Gopalakrishna Shetty
Ananth Kumar Kammella
Sandeep Malampati
Wenbin Shang
Chuanbin Yang
Juxian Song
Sookja Chung
Jiandong Huang
Kaliappan Ilango
Quan-Bin Han
Min Li
spellingShingle Siva Sundara Kumar Durairajan
Ashok Iyaswamy
Sravan Gopalakrishna Shetty
Ananth Kumar Kammella
Sandeep Malampati
Wenbin Shang
Chuanbin Yang
Juxian Song
Sookja Chung
Jiandong Huang
Kaliappan Ilango
Quan-Bin Han
Min Li
A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
Scientific Reports
author_facet Siva Sundara Kumar Durairajan
Ashok Iyaswamy
Sravan Gopalakrishna Shetty
Ananth Kumar Kammella
Sandeep Malampati
Wenbin Shang
Chuanbin Yang
Juxian Song
Sookja Chung
Jiandong Huang
Kaliappan Ilango
Quan-Bin Han
Min Li
author_sort Siva Sundara Kumar Durairajan
title A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
title_short A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
title_full A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
title_fullStr A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
title_full_unstemmed A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease
title_sort modified formulation of huanglian-jie-du-tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of alzheimer’s disease
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-07-01
description Abstract Alzheimer’s disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques. Recently we have identified a novel function of a patented formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese herbal medicine, in treating AD in in vitro studies (US patent No. 9,375,457). HLJDT-M is a formulation composed of Rhizoma Coptitis, Cortex Phellodendri and Fructus Gardeniae without Radix Scutellariae. Here, we assessed the efficacy of HLJDT-M on a triple transgenic mouse model of AD (3XTg-AD). Oral administration of HLJDT-M ameliorated the cognitive dysfunction of 3XTg-AD mice and lessened the plaque burden. In addition, biochemical assays revealed a significant decrease in levels of detergent-soluble and acid-soluble Aβ via decreasing the levels of full length amyloid-β precursor protein (FL-APP) and C-terminal fragments of APP (CTFs) in brain lysates of HLJDT-M-treated mice. HLJDT-M treatment also significantly reduced the levels of FL-APP and CTFs in N2a/SweAPP cells. In contrast, treatment using the classical formula HLJDT did not reduce the memory impairment of 3XTg-AD mice and, rather, increased the Aβ/Fl-APP/CTFs in both animal and cell culture studies. Altogether, our study indicates that HLJDT-M is a promising herbal formulation to prevent and/or cure AD.
url https://doi.org/10.1038/s41598-017-06217-9
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