The Effect of Traditional Chinese Medicine Zhike-Houpu Herbal Pair on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats After Chronic Unpredictable Mild Stress

Abstract

Objective Zhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to treat gastrointestinal motility dysfunction. Recently, many researchers have found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol have antidepressant effects. However, little is known about the antidepressant mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the antidepressant-like effects of ZKHPHP and its possible mechanism of action on 5-hydroxytryptamine receptor 1A (HTR1A) in the hippocampus CA1 region in rats exposed to chronic unpredictable mild stress. Methods Male Sprague Dawley rats were randomly divided into the following six groups: normal, model, ZKHPHP (3 g/kg), ZKHPHP (10 g/kg), ZKHPHP (20 g/kg), and ZKHPHP (30 g/kg); n = 8 per group. We exposed the rats to chronic unpredictable mild stress and then assessed antidepressant-like effects of ZKHPHP by measuring weight change, observing the open-field test, and measuring sucrose water consumption. The antidepressant mechanism was examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A mRNA expression in the hippocampus CA1 region by using immunohistochemistry analysis, Western blotting, and real-time reverse transcription-polymerase chain reaction. Results ZKHPHP (10 or 20 g/kg) reduced the incidence of depressive-like behaviors and increased HTR1A protein and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive behavior, whereas ZKHPHP (3 or 30 g/kg) had no obvious effect on the measured depression indicators. Conclusions These data show that ZKHPHP has antidepressant-like effects based on a chronic unpredictable mild stress-induced depression model in rats. ZKHPHP may be attractive as an antidepressant because of its beneficial effects on depression and the absence of gastrointestinal dysregulation, which is a frequently observed unintended effect of many commonly used antidepressive medications.

Optimization of food deprivation and sucrose preference test in SD rat model undergoing chronic unpredictable mild stress

“…Depression is a chronic heterogeneous mental disease associated with high prevalence, recurrence, and mortality, with serious implications for human physical and mental health 1‐4 . The World Health Organization has predicted that by 2020 it will become the second leading cause of disability worldwide and by 2030 major depressive disorders (MDDs) will represent the main cost in healthcare spending 5,6 . Although progress has been made in the research and treatment of depression in recent years, the exact pathogenesis of this disease is still not clear, and experimental results from animal models are not in good agreement with those of clinical trials 7 .…”

Rapid antidepressant‐like effect of Fructus Aurantii depends on cAMP‐response element binding protein/Brain‐derived neurotrophic facto by mediating synaptic transmission

“…Chinese herb medicines have been widely used for treating mood disorders including depression (Choi et al, 2017; Xia et al, 2019; Xue et al, 2013; Zhang et al, 2015; Zhang et al, 2020). Several studies study found that chronic FRA administration had antidepressant‐like effects in rats in behavioral tests (Shi et al, 2020; Sun, Feng, & Yu, 2012; Zhang et al, 2012; Zhang et al, 2018).…”

The impact of HTR1A and HTR1B methylation combined with stress/genotype on early antidepressant efficacy

“…[51][52][53] Furthermore, Xia Z et al found that CUMS rats displayed significantly decreased HTR1A mRNA compared with the normal group. 54 In clinical research, patients with low HTR1A methylation from À340 to À149 bp upstream of TSS showed overexpression of HTR1A. 55 Furthermore, HTR1A-2-172 is À207 bp upstream of TSS and HTR1A-2-196 is À183 bp upstream of TSS.…”