TY - JOUR
T1 - Qingyangshen mitigates amyloid-β and Tau aggregate defects involving PPARα-TFEB activation in transgenic mice of Alzheimer's disease
AU - Iyaswamy, Ashok
AU - Krishnamoorthi, Senthil Kumar
AU - Zhang, Huan
AU - SREENIVASA MURTHY, Sravan G. S.
AU - Zhu, Zhou
AU - Liu, Jia
AU - Su, Cheng Fu
AU - Guan, Xin Jie
AU - Wang, Zi Ying
AU - Cheung, King Ho
AU - Song, Juxian
AU - Durairajan, Siva Sundara Kumar
AU - Li, Min
N1 - Funding Information:
Some of our grants sponsored this research work HMRF 13144471 from the Health Medical Research Fund, Food and Health Bureau , Hong Kong S.A.R. ( HMRF 17182541 , HMRF 17182551 , HMRF-17182561 ). The Hong Kong General Research Fund ( GRF/HKBU12101417 , GRF/HKBU12100618 ), and research fund from Hong Kong Baptist University ( HKBU/RC-IRCs/17–18/03 , IRCMS/19-20/H02 ) and ( GDS-84/506/2019 ). We thank Prof. Sookja K. Chung and Prof. J.D. Huang for offering the animal behavior facility for the whole research work. We thank Dr. Carol Chu for her enormous support in ordering reagents and managing our lab needs. We thank Dr. Martha Dahlen for her English editing.
Publisher Copyright:
© 2021
PY - 2021/10
Y1 - 2021/10
N2 - Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs) is the key pathological hallmark of AD. Accumulating evidence suggest that impairment of autophagy-lysosomal pathway (ALP) plays key roles in AD pathology.Purpose: The present study aims to assess the neuroprotective effects of Qingyangshen (QYS), a Chinese herbal medicine, in AD cellular and animal models and to determine its underlying mechanisms involving ALP regulation. Methods: QYS extract was prepared and its chemical components were characterized by LC/MS. Then the pharmacokinetics and acute toxicity of QYS extract were evaluated. The neuroprotective effects of QYS extract were determined in 3XTg AD mice, by using a series of behavioral tests and biochemical assays, and the mechanisms were examined in vitro.Results: Oral administration of QYS extract improved learning and spatial memory, reduced carboxy-terminal fragments (CTFs), amyloid precursor protein (APP), Aβ and Tau aggregates, and inhibited microgliosis and astrocytosis in the brains of 3XTg mice. Mechanistically, QYS extract increased the expression of PPARα and TFEB, and promoted ALP both in vivo and in vitro.Conclusion: QYS attenuates AD pathology, and improves cognitive function in 3XTg mice, which may be mediated by activation of PPARα-TFEB pathway and the subsequent ALP enhancement. Therefore, QYS may be a promising herbal material for further anti-AD drug discovery.
AB - Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs) is the key pathological hallmark of AD. Accumulating evidence suggest that impairment of autophagy-lysosomal pathway (ALP) plays key roles in AD pathology.Purpose: The present study aims to assess the neuroprotective effects of Qingyangshen (QYS), a Chinese herbal medicine, in AD cellular and animal models and to determine its underlying mechanisms involving ALP regulation. Methods: QYS extract was prepared and its chemical components were characterized by LC/MS. Then the pharmacokinetics and acute toxicity of QYS extract were evaluated. The neuroprotective effects of QYS extract were determined in 3XTg AD mice, by using a series of behavioral tests and biochemical assays, and the mechanisms were examined in vitro.Results: Oral administration of QYS extract improved learning and spatial memory, reduced carboxy-terminal fragments (CTFs), amyloid precursor protein (APP), Aβ and Tau aggregates, and inhibited microgliosis and astrocytosis in the brains of 3XTg mice. Mechanistically, QYS extract increased the expression of PPARα and TFEB, and promoted ALP both in vivo and in vitro.Conclusion: QYS attenuates AD pathology, and improves cognitive function in 3XTg mice, which may be mediated by activation of PPARα-TFEB pathway and the subsequent ALP enhancement. Therefore, QYS may be a promising herbal material for further anti-AD drug discovery.
KW - Alzheimer's disease
KW - Autophagy-lysosomal pathway
KW - Qingyangshen
KW - Transcriptional factor EB
UR - http://www.scopus.com/inward/record.url?scp=85111305841&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2021.153648
DO - 10.1016/j.phymed.2021.153648
M3 - Journal article
C2 - 34332287
AN - SCOPUS:85111305841
SN - 0944-7113
VL - 91
JO - Phytomedicine
JF - Phytomedicine
M1 - 153648
ER -
