TY - JOUR
T1 - Yuan-Hu Zhi Tong Prescription Mitigates Tau Pathology and Alleviates Memory Deficiency in the Preclinical Models of Alzheimer’s Disease
AU - Iyaswamy, Ashok
AU - Krishnamoorthi, Senthil Kumar
AU - Liu, Y. W.
AU - Song, Juxian
AU - Kammala, Ananth Kumar
AU - Sreenivasmurthy, Sravan Gopalkrishnashetty
AU - Malampati, Sandeep
AU - Tong, Chun Kit Benjamin
AU - Selvarasu, Karthikeyan
AU - Cheung, King Ho
AU - Lu, Jiahong
AU - Tan, Jieqiong
AU - Huang, Chi-Ying
AU - Durairajan, Siva Sundara Kumar
AU - Li, Min
N1 - Funding Information:
This study was supported by the grants of Hong Kong Health and Medical Research Fund (HMRF 12132061, HMRF 14150811, HMRF 15163481, HMRF 17182541, HMRF 17182551), the General Research Fund from Hong Kong Government SAR (GRF/HKBU 12101417, GRF/HKBU 12100618), and research grant from the Hong Kong Baptist University (HKBU/RC-IRCs/17–18/03). This study also supported by the National Natural Science Foundation, China (NSFC 81773926, NSFC 81703487) and Shenzhen Science and Technology Innovation Commission, China (JCYJ20180507184656626, JCYJ20180302174028790).
Publisher copyright:
© 2020 Iyaswamy, Krishnamoorthi, Liu, Song, Kammala, Sreenivasmurthy, Malampati, Chun-Kit Tong, Selvarasu, CHEUNG, Lu, Tan, Huang, Durairajan and Min.
PY - 2020/10/30
Y1 - 2020/10/30
N2 - Alzheimer’s disease (AD) is characterized by memory dysfunction, Aβ plaques together with phosphorylated tau-associated neurofibrillary tangles. Unfortunately, the present existing drugs for AD only offer mild symptomatic cure and have more side effects. As such, developments of effective, nontoxic drugs are immediately required for AD therapy. Present study demonstrates a novel role of Chinese medicine prescription Yuan-Hu Zhi Tong (YZT) in treating AD, and it has substantiated the in vivo effectiveness of YZT in two different transgenic mice models of AD, namely P301S tau and 3XTg-AD mice. Oral treatment of YZT significantly ameliorates motor dysfunction as well as promotes the clearance of aggregated tau in P301S tau mice. YZT improves the cognitive function and reduces the insoluble tau aggregates in 3XTg-AD mice model. Furthermore, YZT decreases the insoluble AT8 positive neuron load in both P301S tau and 3XTg-AD mice. Using microarray and the “Connectivity Map” analysis, we determined the YZT-induced changes in expression of signaling molecules and revealed the potential mechanism of action of YZT. YZT might regulate ubiquitin proteasomal system for the degradation of tau aggregates. The research results show that YZT is a potential drug candidate for the therapy of tau pathogenesis and memory decline in AD.
AB - Alzheimer’s disease (AD) is characterized by memory dysfunction, Aβ plaques together with phosphorylated tau-associated neurofibrillary tangles. Unfortunately, the present existing drugs for AD only offer mild symptomatic cure and have more side effects. As such, developments of effective, nontoxic drugs are immediately required for AD therapy. Present study demonstrates a novel role of Chinese medicine prescription Yuan-Hu Zhi Tong (YZT) in treating AD, and it has substantiated the in vivo effectiveness of YZT in two different transgenic mice models of AD, namely P301S tau and 3XTg-AD mice. Oral treatment of YZT significantly ameliorates motor dysfunction as well as promotes the clearance of aggregated tau in P301S tau mice. YZT improves the cognitive function and reduces the insoluble tau aggregates in 3XTg-AD mice model. Furthermore, YZT decreases the insoluble AT8 positive neuron load in both P301S tau and 3XTg-AD mice. Using microarray and the “Connectivity Map” analysis, we determined the YZT-induced changes in expression of signaling molecules and revealed the potential mechanism of action of YZT. YZT might regulate ubiquitin proteasomal system for the degradation of tau aggregates. The research results show that YZT is a potential drug candidate for the therapy of tau pathogenesis and memory decline in AD.
KW - Alzheimer’s disease
KW - Chinese medicine
KW - connectivity map
KW - microarray
KW - neurofibrillary tangles
KW - P301S tau mice
KW - yuan-hu zhi tong
UR - http://www.scopus.com/inward/record.url?scp=85096121976&partnerID=8YFLogxK
U2 - 10.3389/fphar.2020.584770
DO - 10.3389/fphar.2020.584770
M3 - Journal article
AN - SCOPUS:85096121976
SN - 1663-9812
VL - 11
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 584770
ER -