Hericerin derivatives fromHericium erinaceusexert BDNF-like neurotrophic activity in central hippocampal neurons and enhance memory

Abstract

The traditional medicinal mushroom Hericium erinaceus has long been known for enhancing the peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. It was also reported to protect against ageing-dependent cognitive decline in wildtype and in Alzheimer’s disease mouse models suggesting a yet to be defined action on neurons of the central nervous system. Here, we purified and identified biologically active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom together with its hydrophobic derivative hericene A, were highly potent in inducing extensive axon outgrowth and neurite branching in the absence of serum demonstrating high neurotropic activity. NDPIH also induced enlarged growth cones suggestive of a brain-derived neurotrophic factor (BDNF)-like activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA12 prevented NDPIH-induced neurotrophic activity providing evidence that NDPIH acts via TrkB receptors to mediate its neurotrophic effect in central neurons. Finally, in vivo treatment with H. erinaceus crude extract and hericene A significantly increased BDNF and downstream pathway and enhanced learning and memory in the novel object recognition memory test. Our results suggest that hericene A can promote BDNF-like activity in neurons in vitro and in vivo thereby enhancing recognition memory.

Lion’s Mane (Hericium erinaceus) Exerts Anxiolytic Effects in the rTg4510 Tau Mouse Model

“…This is also one of the first studies to assess the effects of H. erinaceus on both female and male mice. Previous literature assessing the effects of H. erinaceus has only used either male [ 11 , 50 , 53 ] or female mice [ 16 ], and has not assessed both sexes, with the majority of studies primarily assessing the effects on male mice.…”

“…This is the first study demonstrating that H. erinaceus has anxiolytic effects in the rTg4510 tau mouse model. Previous research has shown this in relation to amyloid and WT mouse models but has not demonstrated it in a strictly tau mouse model [11,16,50,53]. Many other studies have assessed the cognitive effects of H. erinaceus in other models of AD or cognitive decline/aging such as APP/swePS1dE9 [16,20], SAMP8 [54], ICR (Institute of Cancer Research) mice with injected amyloid peptides [15], and Sprague Dawley rats injected with d-galactose [44].…”

The Acute and Chronic Effects of Lion’s Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study

“…Interestingly, both hericenones and erinacines can easily cross the blood-brain barrier [10]; promote nerve growth factor synthesis and secretion [11,12]; and, in animal models, have been shown to exert anti-neuroinflammatory and neuroprotective properties [4,[13][14][15] and promising cognition-enhancing effects [16,17]. Additionally, an increase in circulating pro-brain-derived neurotrophic factor (BDNF) has been observed following hericene A (isolated from H. erinaceus) administration in mice [18]. The same effect was observed, alongside memory and mood enhancements, in overweight humans following H. erinaceus extract supplementation [19], suggesting a general effect on BDNF synthesis and a BDNF-like neurotrophic effect of H. erinaceus and its derivatives.…”