Combination of Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma Alleviates Learning and Memory Impairment in Scopolamine-Treated Mice by Regulating Synaptic-Related Proteins.

Funan Ning,Lvyi Chen,Kun Shi,Xin Liu,Linlin Chen,Yao Zhu,Jiayi Hu,Jiaxuan Xia,Zhou Lan,Ping Wang,Guangjing Xie

doi:10.3389/fphar.2021.679573

Abstract

Polygoni Multiflori Radix Praeparata (ZhiHeShouWu, PMRP) and Acori Tatarinowii Rhizoma (ShiChangPu, ATR) and their traditional combination (PA) are frequently used in traditional Chinese medicine to prevent and treat Alzheimer disease (AD) based on the theory that PMRP tonifies the kidney and ATR dissipates phlegm. However, the components of PA and their mechanisms of action are not known. The present study analyzed the active components of PA, and investigated the protective effect of PA against cognitive impairment induced by scopolamine in mice along with the underlying mechanism.The aqueous extract of PA was analyzed by high-performance liquid chromatography–mass spectrometry (HPLC-MS) and gas chromatography (GC)-MS in order to identify the major components. To evaluate the protective effect of PA against cognitive dysfunction, mice were orally administered PA, PMRP, or ATR for 30 days before treatment with scopolamine. Learning and memory were assessed in mice with the Morris water maze test; neurotransmitter levels in the hippocampus were analyzed by HPLC-MS; and the expression of synapse-related proteins in the hippocampus was detected by western blotting and immunohistochemistry. Eight active compounds in PA and rat plasma were identified by HPLC-MS and GC-MS. Plasma concentrations of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside, emodin, α-asarone, and asarylaldehyde were increased following PA administration; meanwhile, gallic acid, emodin-8-O-β-d-glucopyranoside, β-asarone, and cis-methyl isoeugenol concentrations were similar in rats treated with PA, PMRP, and ATR. In scopolamine-treated mice, PA increased the concentrations of neurotransmitters in the hippocampus, activated the brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) signaling pathway, and increased the expression of p90 ribosomal S6 kinase (p90RSK) and postsynaptic density (PSD)95 proteins. Thus, PA alleviates cognitive deficits by enhancing synaptic-related proteins, suggesting that it has therapeutic potential for the treatment of aging-related diseases such as AD.

Highlights

Most aging-associated neurodegenerative disorders, including Alzheimer disease (AD) are characterized by progressive memory loss and learning deficits
Tang Rongchuan stated in the book of “Essence of Chinese and Western Huitong Medical Classics” that the reason why things are not forgotten depends on the memory, and memory is recorded in the kidney meridian
PMRP had a broad range of pharmacologic activities including anti-aging and neuroprotective effects Li et al (2005), Kim et al (2013), Niu et al (2014), and ATR can improve memory and cognitive function (Deng et al, 2015)

Summary

Introduction

Most aging-associated neurodegenerative disorders, including Alzheimer disease (AD) are characterized by progressive memory loss and learning deficits. The main drugs used for AD treatment are AChE inhibitors such as donepezil, galantamine, and tacrine, which reduce extrasynaptic metabolism of ACh and thereby enhance its concentration at the synaptic cleft Ionita et al (2018); and N-methyl-D-aspartic acid glutamate receptor antagonists such as memantine (Tayeb et al, 2012). These drugs only slow the deterioration of cognitive function and do not promote neuronal survival; they have various adverse effects including nausea, diarrhea, and vomiting. There is a need for novel agents for AD treatment that are better tolerated and effective

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Conclusion