Abstract
Herb-pairs are the basic units of composition in Chinese herbal formulae, where the bridge linking Chinese medicine and prescription consists of two Chinese medicine herbs. The Suanzaoren-Wuweizi herb-pair (SWHP) is commonly used as a sedative or tranquilizer. SWHP has been demonstrated to exert an antianxiety effect in animal models of anxiety. However, little information about its mechanism is available and the effects of SWHP have not been investigated. This study examined the effects of SWHP on ameliorating anxiety-like behaviors by regulating endocannabinoids system (ECS)—brain-derived neurotrophic factor (BDNF)—extracellular regulated protein kinases (ERK) signaling pathway expression, induced by restraint stress (RS) procedures. The antianxiety effects of SWHP on RS rats were then examined through the open-field test (OF) and the elevated plus maze test (EPM). The concentration of BNDF, ERK1/2, p-ERK1/2, cAMP-response element binding protein (CREB), and p-CREB expression in the prefrontal cortex and hippocampus of the rats was then measured by western blot. The number of positive cells of CB1 and CB2 in the rats' hippocampus CA1 region was measured by immunohistochemistry. These results gave compelling evidence that SWHP could modify anxiety-like behaviors of RS rats through regulation of the ECS-BDNF-ERK signaling pathway. Our study demonstrated that SWHP improved anxiety-like behaviors in RS rat models by regulating the ECS-BDNF-ERK signaling pathway. The findings indicate that SWHP may have a therapeutic application in the RS model of anxiety disorder, which proposes a potential new direction for research into anxiety disorders regarding mechanisms and the development of novel antianxiety drugs.
Highlights
Anxiety disorder is a nervous disorder characterized by anxiety, tension, panic, autonomic nervous disorder, muscle tension, and other symptoms
Western blot analyses showed that phosphorylation of cAMP-response element binding protein (CREB) (p-CREB) was significantly increased in the prefrontal cortex and hippocampus after restraint stress (RS) when compared with control groups. e p-CREB expression in these two brain regions was reversed by treatment with Suanzaoren-Wuweizi herb-pair (SWHP) at doses of 1.5 g/kg and 3.0 g/kg
A study indicated that the levels of p-extracellular regulated protein kinases (ERK) were significantly increased during anxiety, and the results suggested that the ERK signal transduction pathway might play an important role in anxiety, suggesting that the inhibition of the ERK pathway phosphorylation could produce an anxiolysis effect [57]. e results of our study indicate that RS model activated ERK-CREB signaling pathway, which increased the p-ERKl/2 and p-CREB (Figure 6), and SWHP significantly inhibited the hyperphosphorylation of ERK1/2 and CREB (Figure 6)
Summary
Anxiety disorder is a nervous disorder characterized by anxiety, tension, panic, autonomic nervous disorder, muscle tension, and other symptoms. Anxiety disorders are among the costliest mental disorders, regarding both morbidity and economic costs [2, 3] Antianxiety drugs such as diazepam, benzodiazepines, and selective serotonin reuptake. Regarding SSRIs, the MHRA and FDA warned that SSRIs increased the risk of suicidal behavior and self-harm, and were of minimal benefit when it came to the treatment of children and adolescents [7, 8]. Side effects such as these limit their use in clinics. Side effects such as these limit their use in clinics. e development of anxiety-reducing (anxiolytic) drugs has been a major focus in both pharmaceutical industries and academic neuropsychiatric research [9, 10]
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