Beneficial Effects of Crocin against Depression via Pituitary Adenylate Cyclase-Activating Polypeptide

Author:

Lu Linyu1ORCID,Wu Die1ORCID,Wang Kai1ORCID,Tang Juanjuan1ORCID,Chen Gang23ORCID

Affiliation:

1. School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

2. Interdisciplinary Institute for Personalized Medicine in Brain Disorders, and Research Center for Formula and Syndromes, Jinan University, Guangzhou 510632, China

3. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 226001, China

Abstract

Depression is one of the foremost psychological illness, and the exact mechanism is unclear. Recent studies have reported that the pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathway is involved in the progression of depression. In the present study, we extracted crocin from the traditional Chinese medicine (TCM), Gardenia jasminoides Ellis, to evaluate its antidepressant effect and clarify the underlying mechanism. Here, we established a chronic unpredictable mild stress (CUMS) mouse model to assess whether crocin can improve depression-like behavior in an open field test (OFT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT). A corticosterone (CORT) model of PC12 was set up to explore the antidepressant mechanism of crocin. We pretreated PC12 cells with crocin for 1 hour and then stimulated the cells with CORT for 24 hours. Cell survival was detected by Hoechst staining and MTT assay. The expression of PACAP, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and extracellular regulated protein kinases (ERK) were analyzed by western blotting. PACAP RNAi was used to interfere with PC12 cells to downregulate the content of PACAP. The results showed that crocin (30 mg/kg) significantly reversed the decrease of body weight and elevation of serum CORT, mitigated CUMS induced depression-like behaviors of mice, and crocin (12.5 μmol/L) protected PC12 cells against CORT (200 μmol/L)-induced injury. Furthermore, crocin greatly increased the protein expression of PACAP and phosphorylation of ERK and CREB in the CORT model. PACAP RNAi cancelled the neuroprotective effect of crocin. In conclusion, these results indicated that crocin exerted an antidepressant effect via upregulating PACAP and its downstream ERK and CREB signaling pathways.

Funder

Natural Science Foundation of Jiangsu Province

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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