Abstract

The study aimed to explore the antidepressant effect of Yinhuo Decoction and further to explore its underlying molecular mechanism acting on depressant. Here, high-performance liquid chromatography (HPLC) analysis was used to the composition analysis. Postmenopausal depression (PMD) model and corticosterone (CORT)-induced cell model were constructed. Adrenal coefficient and hematoxylin and eosin staining were applied to assess changes in the adrenal glands. MTT staining, Hoechst 33342 staining, and JC-1 fluorescence staining were used to detect the PC12 activity and apoptosis. CORT and oxidative stress indicators were measured using commercial kits. Western blot and immunohistochemical were used to detect the protein expression of GCR. In addition, genes related to SIRT1/PGC-1α pathway were also tested. In PMD model mice, Yinhuo Decoction evidently increased adrenal coefficient and relieved adrenal lesions. Meanwhile, we observed that Yinhuo Decoction reduced the CORT and GCR levels. In CORT-treated PC12 cells, Yinhuo Decoction remarkably reduced cytotoxicity and apoptosis. Besides, Yinhuo Decoction attenuated the oxidative stress response. Mechanically, we confirmed that Yinhuo Decoction reduced CORT-induced PC12 damage by regulating SIRT1/PGC-1α pathway. Thus, we concluded that Yinhuo Decoction antagonized CORT-induced injury in PC12 cells and improved depression in PMD mice. This provided a new direction for the treatment of depression.

Highlights

  • To detect whether the Yinhuo Decoction affected the oxidative stress of the PC12 cells, we evaluated the indicators related to oxidative stress

  • 50 μm Yinhuo decoction 50 μm According to report, the HPA axis hyperfunction is one of the pathogenesis of depression, and most patients suffered with depression have different degrees of HPA axis dysfunction [12]

  • Our finding revealed that Yinhuo Decoction significantly increased adrenal coefficient and relieved adrenal lesions

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Summary

Introduction

Depression is a chronic and life-threatening mental illness caused by a variety of factors. Its main symptom is a psychological or emotional disorder, affecting approximately 350 million people around the world [1, 2]. Suffering from depression increases the risk of potentially fatal diseases, such as cardiovascular and cerebrovascular diseases and neurodegenerative diseases [3]. Major depression is ranked as the third most common disease burden in the world and is predicted to rank first by 2030 [4, 5]. A large number of antidepressants have been developed for clinical use, their therapeutic efficacy is far from satisfactory. Only about 30% of patients with major depression respond to current antidepressant, while about 70% of responders do not achieve the complete remission [6] more and more researchers began to pay attention to the pathogenesis of depression and drugs with potential therapeutic targets

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