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

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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.


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.


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.


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.

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