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Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant‐Like Effects in Olfactory Bulbectomized Mice

Matsui, Nobuaki, Akae, Haruka, Hirashima, Nana, Kido, Yuki, Tanabe, Satoshi, Koseki, Mayumi, Fukuyama, Yoshiyasu, Akagi, Masaaki
Phytotherapy research 2016 v.30 no.11 pp. 1856-1861
Magnolia officinalis, Western blotting, animal models, antidepressants, magnolol, mice, mitogen-activated protein kinase, neurogenesis, neurons, neurotrophins, non-specific serine/threonine protein kinase, phosphorylation, signal transduction, tail suspension test
Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain‐derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin‐related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5‐bromo‐2′‐deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX‐induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein after 3 h. The present data indicate that magnolol exerts antidepressant‐like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin‐related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.