Action mechanisms of Oviductus ranae on perimenopausal depression model mice via regulation of phosphoinositol 3 kinase/AKT signalling

Abstract

Oviductus ranae (OR) is an animal-based traditional Chinese medicine. In this work, its underlying mechanism of action in mice model of perimenopausal depression (PMD) was investigated. Network pharmacology and molecule docking analysis were conducted to identify potential targets and chemical components of OR in PMD. Subsequently, 60 female mice were ovariectomized and subjected to chronic unpredictable mild stress to establish the PMD model. After 14 days of OR administration on PMD mice, the depression-like behavioral were evaluated using sucrose preference, forced swimming, tail suspension, open field and morris water maze tests. Hippocampal tissues were collected to observe pathological changes via haematoxylin-eosin (H&E) staining, and immunohistochemical analysis was performed to detect the expression of the protein kinase B (AKT), phosphoinositol 3 kinase (PI3K), and oestrogen receptor β (ERβ). Western blot (WB) analysis was Conducted to detect the expression of PI3K/AKT signalling pathway. In the results, 18 potential targets and two chemical components of OR in PMD were identified. KEGG suggested that the PI3K/AKT signaling pathway was frequently involved in treatment of PMD with OR. Molecular docking showed that β-sitosterol in OR had the best docking effect with the target. OR treatment improved depression-like behaviour of PMD mice, significantly improved pPI3K/PI3K, pAKT/AKT, and pCREB/CREB ratios and brain derived neurotrophic factor. These findings suggested that OR may alleviate PMD and increase brain-derived neurotrophic factor levels, and has a certain therapeutic effect on PMD by up-regulating the expression of ERβ and activating the PI3K/AKT pathway. Overall, our study highlights OR as a promising therapeutic candidate for PMD.