Mar 2019
Paula Sassoli Fazan ValeriaCorresponding author
Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Av. Bandeirantes 3900, Ribeirao Preto-SP, Brazil
We used a behavioral test to investigate long-term consequences of neonatal noxious stimulus in the anxiety-like behavior and describe differences between males and females. Male and female Wistar rats were submitted to either tactile (control groups) or noxious stimulus (pain groups) since birth, for 15 days and were followed up to 6 months of life. Experiments were performed on days 15, 30, 90 and 180 after birth. Rats of different groups, ages and genders were exposed only once to the elevated plus-maze (EPM), an apparatus largely used to detect anxiety-related behaviors in rats. For the open arms of the EPM, control animals showed an increase in the number of entries from 15 to 30 days of age followed by a decrease of this number at older ages. The comparison between treatments (control and pain) showed, for males, a reduced number of entries in the open arms in the pain group at 15 and 30 days and the opposite situation at 180 days. No differences were found between pain and control groups in females. Our results are in agreement with the literature that shows sex-dependent changes following chronic stress; stress being anxiolytic in males and anxiogenic in females. We point to the fact that acute painful stimulus in the neonatal period caused persistent changes in anxiety-like behavior in the adult life, independently of previously described intrinsic gender differences on memory, task performance, attention bias or other behaviors.
Dec 2025
Liu LipingCorresponding author
The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.