Combination of syringaresinol\u2013di\u2013O\u2013\u03b2-d-glucoside and chlorogenic acid shows behavioral pharmacological anxiolytic activity and activation of hippocampal BDNF\u2013TrkB signaling

Shouhei Miyazaki,Takahiko Fujikawa,Hideo Takekoshi,Hirotaka Oikawa,Masato Ogata,Yoshio Fujita,Hideaki Soya

doi:10.1038/s41598-020-74866-4

Abstract

Mental stress, such as anxiety and conflict, causes physiological changes such as dysregulation of autonomic nervous activity, depression, and gastric ulcers. It also induces glucocorticoid production and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels. We previously reported that Acanthopanax senticosus HARMS (ASH) exhibited anxiolytic activity. Thus, we attempted to identify the anxiolytic constituents of ASH and investigated its influence on hippocampal BDNF protein expression in male Sprague Dawley rats administered chlorogenic acid (CHA), ( +)-syringaresinol–di–O–β-d-glucoside (SYG), or a mixture of both (Mix) for 1 week using the open field test (OFT) and improved elevated beam walking (IEBW) test. As with ASH and the benzodiazepine anxiolytic cloxazolam (CLO), Mix treatment significantly increased locomotor activity in the OFT. CHA and Mix increased the time spent in the open arm in the IEBW test. SYG and Mix treatment inhibited the significant increase in normalized low-frequency power, indicative of sympathetic nervous activity, and significant decrease in normalized high-frequency power, indicative of parasympathetic nervous activity, as observed in the IEBW test. SYG and Mix treatment significantly increased hippocampal BDNF protein expression. The combination of CHA and SYG possibly induces anxiolytic behavior and modulates autonomic regulation, activates hippocampal BDNF signaling as with ASH.

Highlights

Stress, induced by alterations of the external environment, affects the autonomic nervous system (ANS) as well as the hypothalamus–pituitary–adrenal (HPA) axis
Using the open field test (OFT), Jin L. et al.reported that Acanthopanax senticosus HARMS (ASH) extract does not change numbers of zone crosses and rearing in mice[14]
ASH and mixture of both (Mix) ameliorated behavioral restraint induced by anxiety or fear in novel environments; they did not affect thigmotaxis, as reported by Jin L. et al The increase in locomotor activity in the open field due to benzodiazepines is believed to be caused by the cancellation of anxiety-induced behavioral inhibition

Summary

Introduction

Stress, induced by alterations of the external environment, affects the autonomic nervous system (ANS) as well as the hypothalamus–pituitary–adrenal (HPA) axis. The HPA axis induces various responses to counter environmental change (partially overlapping with SNS) by stimulating the secretion of steroid hormones and adrenaline into circulation Chronic stress, such as long-term anxiety, induces gastric ulcers and depression via activation of the HPA axis and ANS5,6. We previously reported that ASH extract prevents the onset of gastric ulcers induced by restraint stress in w ater[12]. CHA and SYG, which are present in high concentrations among ASH extract components, prevent stress-induced gastric ulcer[12]. The anxiolytic effects of CHA induced via G ABAA receptors has been reported[30] These findings suggest that psychological stress resistance induced by ASH occurs through effects on the central nervous system (CNS). Components of ASH that contribute to effects on hippocampal BDNF signaling in the hippocampus have not been investigated

Methods

Results

Conclusion