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

Abstract

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.

Pharmacology, Toxicity, Bioavailability, and Formulation of Magnolol: An Update

“…Ameliorated depression-like behavior and hippocampal nerve injury significantly Matsui et al (2016) Male SD rats subjected to unpredictable CMS (UCMS)…”

“…Qiu et al expression levels of brain-derived neurotrophic factor (BDNF), serotonergic system activity, such as nerve inflammation, and the prefrontal cortex oxidative stress (Li et al, 2012, Li LF et al, 2013Matsui et al, 2016;Bai et al, 2018;Cheng et al, 2018). MG was a dual agonist of PPAR-γ (EC 50 0.93 ± 0.91 µM) and RXRα (EC 50 3.91 ± 1.08 µM) (Dreier et al, 2017).…”

The search for, and chemistry and mechanism of, neurotrophic natural products

“…Recently, it was reported that 6 and 7 showed antidepressant-like effects on unpredictable chronic mild stress (UCMS)-treated rats by enhancing BDNF expression and serotonergic activity in the hippocampus [62,63]. Matsui et al reported that 6 significantly improved depressive behavior in olfactory bulbectomized (OBX) mice in the tail suspension test, significantly enhanced hippocampal neurogenesis and increased phosphorylation of Akt and cyclic AMP-responsive element-binding protein (CREB) [64]. These data demonstrate that magnolol (6) has antidepressant-like effects on behaviors and actions by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signaling in mice.…”

Insights on the Multifunctional Activities of Magnolol

“…Magnolol at the doses of 20 and 40 mg/kg shows antidepressant activity and effectively reverses the effects of UCMS [77, 78]. Consistently, magnolol also shows antidepressant activity in an olfactory bulbectomy (OBX) mice model by improvement of impaired hippocampal neurogenesis and increased phosphorylation of extracellular signaling, Akt, ERK, and CREB [79]. In chronic hormone corticosterone (CORT)-induced depressive rats model, the immobility time of FST and tail suspension test (TST) are decreased, along with decreased expression of BDNF, 5-hydroxytryptamine (5-HT), and norepinephrine (NE).…”