title: Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice.
abstract: Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT) in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with thymol significantly restored the CUMS-induced alterations of monoamine neurotransmitters in the hippocampus. Our results further demonstrated that thymol administration negatively regulated the induction of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1. In sum, our findings suggested that thymol played a potential antidepressant role in CUMS mice model through up-regulating the levels of central neurotransmitters and inhibiting the expressions of proinflammatory cytokines, which might provide potential for thymol in the light of opening up new therapeutic avenues for depression.
authors.affiliation: Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xue-Yang
authors.initials: XY
authors.lastname: Deng
authors.affiliation: Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Rui-Peng
authors.initials: RP
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Traditional Chinese Medical Formulae, Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China. Electronic address: qurong@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Qu
authors.affiliation: Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China. Electronic address: fuqiang@cpu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pharmacology of Chinese Materia, China Pharmaceutical University, Nanjing 210009, China. Electronic address: spma@cpu.edu.cn.
authors.forename: Shi-Ping
authors.initials: SP
authors.lastname: Ma
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009638:Norepinephrine / Q000378:metabolism; D011897:Random Allocation; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological; D013943:Thymol / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D002352:Carrier Proteins; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D012701:Serotonin; D013943:Thymol; D020170:Caspase 1; D009638:Norepinephrine
keywords: Antidepressant; NLRP3; Neurotransmitter; Proinflammatory cytokine; Thymol