Abstract
Backgrounds. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Aim of the Study. From traditional Chinese medicine and pharmacogenetics perspectives, the present study aimed to investigate the antidepressant effects of CSS on a mouse model of Liver-Qi Stagnation (LQS) syndrome and its underlying mechanisms. Methods and Materials. We used two main mouse models of depressive syndromes in the study, including LQS and liver stagnation and spleen deficiency (LSSD) syndrome. Tail suspension and forced swimming tests were used to evaluate the effects of CSS on animal behaviour. The expression level of the CYP450 enzyme from liver microsomes was analysed by western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). More specifically, we analysed the key compounds of CSS that are responsible for CYP450 regulation via bioinformatics. Ultimately, luciferase assays were employed to confirm the prediction in vitro. Results. CSS remarkably reduced the immobile time in LQS rather than in LSSD mice. Although CSS significantly upregulated CYP2C9 in mice with both syndromes, activated translation of CYP3A4 induced by CSS was only observed in the LQS group. Bioinformatics analysis revealed that the unique regulation of CYP3A4 was responsible for the effects of glycyrrhetinic acid (GA) from CSS. Further luciferase assays confirmed the enhancement of CYP3A4 expression via the pregnane X receptor (PXR) pathway in vitro. Conclusions. CSS specifically upregulates the translation of CYP3A4 via the PXR pathway in depressed LQS mice. GA, a bioactive compound that originates from CSS, contributes to this activation. This work provides novel insight into Chinese syndrome-based therapy for depression.
Highlights
Depression is a prevalent psychiatric illness characterized by low mood, slow thought, and mental disorder. e World Health Organization (WHO) ranks depression as the leading contributor to global disability, affecting 322 million people [1,2,3,4,5]
After the Liver-Qi Stagnation (LQS) model group was treated with CSS (4 g/kg and 12 g/kg), an evident decrease in immobility time was observed (p < 0.001) (Figures 2(b)–2(f )), while CSS had no influence on liver stagnation and spleen deficiency (LSSD) animals, which means that CSS had no antidepressant effects on LSSD of depression. ese results suggested that CSS attenuated the depressive-like behaviour of LQS depression
Bioinformatics Results Imply at Glycyrrhetinic Acid Is Involved in the Specific Regulation by CSS. e sophisticated compounds of CSS make it difficult to elucidate the therapeutic mechanisms of CYP3A4 regulation following depression
Summary
Depression is a prevalent psychiatric illness characterized by low mood, slow thought, and mental disorder. e World Health Organization (WHO) ranks depression as the leading contributor to global disability, affecting 322 million people [1,2,3,4,5]. Chaihu-Shugan-San (CSS) is a classic prescription used in the clinic to treat depression [8]. Abundant studies have reported the effects of CSS on depression, rodent models of chronic mild stress or unavoidable punishment (learned helplessness) have been adopted for inducing depressive symptoms [15]. According to the theory of traditional Chinese medicine (TCM), depression includes different syndromes, such as Liver-Qi Stagnation (LQS), a syndrome induced by abnormal flow of the liver qi, which is characterized by depression, chest tightness and sighing [16], and liver stagnation and spleen deficiency (LSSD), which includes poor digestion, weight loss, diarrhoea, a bad appetite, and so on [17]; these are the two main depressive syndromes, and each has its own specific symptoms. Further study is indispensable to elucidate the Chinese syndrome-specific efficacy of CSS in depression
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