Abstract
Antidepressant-like effects of ethanolic extract of Hericium erinaceus (HE) mycelium enriched in erinacine A on depressive mice challenged by repeated restraint stress (RS) were examined. HE at 100, 200 or 400 mg/kg body weight/day was orally given to mice for four weeks. After two weeks of HE administration, all mice except the control group went through with 14 days of RS protocol. Stressed mice exhibited various behavioral alterations, such as extending immobility time in the tail suspension test (TST) and forced swimming test (FST), and increasing the number of entries in open arm (POAE) and the time spent in the open arm (PTOA). Moreover, the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were decreased in the stressed mice, while the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were increased. These changes were significantly inverted by the administration of HE, especially at the dose of 200 or 400 mg/kg body weight/day. Additionally, HE was shown to activate the BDNF/TrkB/PI3K/Akt/GSK-3β pathways and block the NF-κB signals in mice. Taken together, erinacine A-enriched HE mycelium could reverse the depressive-like behavior caused by RS and was accompanied by the modulation of monoamine neurotransmitters as well as pro-inflammatory cytokines, and regulation of BDNF pathways. Therefore, erinacine A-enriched HE mycelium could be an attractive agent for the treatment of depressive disorders.
Highlights
Depression, a psychiatric disorder characterized by a low self-esteem, altered mood, hopelessness, reduced interest/pleasure in daily activities and persistent thoughts of death or suicide, has become a significant global health issue and economic burden [1]
The animal models and clinical studies on the link between stress and depressive disorders suggest that antioxidant agents can reduce oxidative stress through scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS), which further protect against neuronal damage induced by stress [5,6,7,8,9]
The chromatograms generated by high-performance liquid chromatogram (HPLC) and liquid-chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS) with positive and negative ionization modes of the ethanolic extract from mycelia of H. erinaceus are displayed in
Summary
Depression, a psychiatric disorder characterized by a low self-esteem, altered mood, hopelessness, reduced interest/pleasure in daily activities and persistent thoughts of death or suicide, has become a significant global health issue and economic burden [1]. The animal models and clinical studies on the link between stress and depressive disorders suggest that antioxidant agents can reduce oxidative stress through scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS), which further protect against neuronal damage induced by stress [5,6,7,8,9]. Stress-induced depression has been shown to alter the levels of monoamine neurotransmitters such as serotonin (5-HT), along with behavioral changes in animal models [10,11]. In the view of the impact on depressors, especially for those suicide-risk patients, research focused on the discovery and development of agents with promising efficacy and fewer side effects is urgent
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