Title:Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and
BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats
Volume: 17
Author(s): Ruifeng Liang, Wenjing Ge, Xianmei Song, Huisen Wang, Weifeng Cui, Xuexia Zhang, Zheng Wei and Gengsheng Li*
Affiliation:
- Institute of Chinese materia medica, Henan Integrative Medicine Hospital, Zhengzhou 450004, Henan, China
Keywords:
Paeoniflorin, IBS, Anxiety behavior, Visceral hypersensitivity, HPA axis, BDNF/TrkB/PLCγ1 pathway.
Abstract:
Background:
Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The
pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction,
which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing
attention.
Objective:
The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced
IBS-like rats.
Methods:
The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of
PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM)
test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic
(EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH),
corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and
immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR),
mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1)
were examined by Western blot.
Results and Discussion:
The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore,
the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered
hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB,
and phospho-PLCγ1 in the colon.
Conclusion:
These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA
axis activity and BDNF/TrkB/PLCγ1 signaling pathway.
