Multi-target regulatory mechanism of Yang Xin Tang - a traditional Chinese medicine against dementia

Tung Yan Lo; Anthony Siu Lung Chan; Suet Ting Cheung; Lisa Ying Yung; Manton Man Hon Leung; Yung Hou Wong

doi:10.1186/s13020-023-00813-w

Multi-target regulatory mechanism of Yang Xin Tang - a traditional Chinese medicine against dementia

Chin Med. 2023 Aug 16;18(1):101. doi: 10.1186/s13020-023-00813-w.

Authors

Tung Yan Lo¹, Anthony Siu Lung Chan¹, Suet Ting Cheung¹, Lisa Ying Yung¹, Manton Man Hon Leung^{1

2}, Yung Hou Wong^{3

4

5

6}

Affiliations

¹ Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China.
² Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
³ Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China. boyung@ust.hk.
⁴ State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Hong Kong, China. boyung@ust.hk.
⁵ Center for Aging Science, Hong Kong University of Science and Technology, Hong Kong, China. boyung@ust.hk.
⁶ Hong Kong Center for Neurodegenerative Diseases, Units 1501-1502, 17 Science Park West Avenue, Hong Kong Science Park, Shatin, New Territories, Hong Kong, China. boyung@ust.hk.

Abstract

Background: Yang Xin Tang (YXT) is a traditional Chinese herbal preparation which has been reported to improve cognitive function and memory in patients with dementia. As the underlying mechanism of action of YXT has not been elucidated, we examined the effects of YXT and its major herbal components in regulating gene transcription and molecular targets related to Alzheimer's disease (AD).

Methods: Aqueous and ethanol extracts of YXT and selected herbal components were prepared and validated by standard methods. A series of biochemical and cellular assays were employed to assess the ability of the herbal extracts to inhibit acetylcholinesterase, reduce β-amyloid aggregation, stimulate the differentiation of neural progenitor cells, suppress cyclooxygenase, and protect neurons against β-amyloid or N-methyl-D-aspartate-induced cytotoxicity. The effects of YXT on multiple molecular targets were further corroborated by a panel of nine reporter gene assays.

Results: Extracts of YXT and two of its constituent herbs, Poria cocos and Poria Sclerotium pararadicis, significantly inhibited β-amyloid aggregation and β-amyloid-induced cytotoxicity. A protective effect of the YXT extract was similarly observed against N-methyl-D-aspartate-induced cytotoxicity in primary neurons, and this activity was shared by extracts of Radix Astragali and Rhizoma Chuanxiong. Although the YXT extract was ineffective, extracts of Poria cocos, Poria Sclerotium pararadicis and Radix Polygalae inhibited acetylcholine esterase, with the latter also capable of upregulating choline acetyltransferase. YXT and its components significantly inhibited the activities of the pro-inflammatory cyclooxygenases. Additionally, extracts of YXT and several of its constituent herbs significantly stimulated the phosphorylation of extracellular signal-regulated kinases and cAMP-responsive element binding protein, two molecular targets involved in learning and memory, as well as in the regulation of neurogenesis.

Conclusions: Several constituents of YXT possess multiple regulatory effects on known therapeutic targets of AD that range from β-amyloid to acetylcholinesterase. The demonstrated neuroprotective and neurogenic actions of YXT lend credence to its use as an alternative medicine for treating AD.

Keywords: Alzheimer’s disease; Chinese medicine; Neural progenitor cell; Neurodegenerative disease; Neuroprotection; Yang Xin Tang; β amyloid.

Abstract

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