Abstract
Major depressive disorder is now becoming a common disease in daily life, and most patients do not have satisfactory treatment outcomes. We herein evaluated the therapeutic effects of Zhile capsule and clarified the molecular mechanism. A rat model of chronic unpredictable mild stress-induced depression was established to assess the antidepressant-like effects of Zhile by using the sucrose preference test, open field test, forced swim test, tail suspension test and HPLC. Systems pharmacology was then performed to unravel the underlying mechanism which was confirmed by western blot, enzyme-linked immunosorbent assay, and qPCR. Zhile alleviated depression-like behaviors by upregulating the cAMP-CREB-BDNF (brain-derived neurotrophic factor) axis to exert neuroprotective effects. It may be beneficial to depressive patients in clinical practice.
Highlights
Over 300 million people are suffering from major depressive disorder worldwide, as the leading cause for disability
To verify whether Zhile capsule (ZL) have antidepressant-like effects on chronic unpredictable mild stress (CUMS) rats, we conducted our experiments as Figure 1A
As an approach for evaluating the antidepressant effects of ZL, sucrose preference test (SPT) was performed after five weeks of CUMS exposure
Summary
Over 300 million people are suffering from major depressive disorder worldwide, as the leading cause for disability. Depression is characterized by dysthymic moods, loss of interest in things once pleasurable, anhedonia, feelings of despair, and loss of motivation. The complexity of this disease is caused by the interplay between multiple inherited genes and exposure to environmental stressors throughout life. Animal models of chronic unpredictable mild stress (CUMS) have been used to study depressive-like behaviors. The neuroprotective and anti-apoptotic effects of ZL on an animal model of CUMS-induced depression or the potential mechanisms are still unclear. Thereby motivated, we evaluated the therapeutic effects of ZL on a rat model of CUMS-induced depression, and explored the molecular mechanism from the perspectives of neuroprotection and apoptosis inhibition. We used a systemic approach to study the possible mechanism due to the complexity and diversity of ingredients in TCM formula, identifying the main pathway of BDNF and apoptosis
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