Erinacine A

In the modern era, cancer can be controlled by chemotherapy treatment, and in many situations a stable disease is obtained. The significant clinical success and subsequent commercialization of naturally derived molecules have further encouraged their exploration as adjunctive therapies in cancer management. The purpose of this comprehensive review is to update the anticancer mechanisms triggered by Erinacine A and regulation of signaling pathways potentially involved in its anticancer activity.The results of preclinical research showed that Erinacin A, a therapeutically important biological metabolite isolated from the basidiomycete fungus Hericium erinaceus offers a multitude of possible chemotherapeutic applications by regulating complex signaling pathways as validated by various pharmacological in vitro and in vivo studies. As a result of Erinacin A's action on oncological signaling pathways, it resulted in induction of apoptosis, reduction of proliferation, invasiveness, generation of oxidative stress and cell cycle arrest in cancer cells.

Maintaining glutamate homeostasis through astrocyte-enriched glutamate transporter 1 (GLT-1) is critical for neuronal survival, but it is often disrupted after brain injury. Hericium erinaceus (HE), an edible mushroom, was reported to be anti-inflammatory and neuroprotective against brain ischemia, but its effect on glutamate homeostasis was unknown. Here we investigated the neuroprotective effect of erinacine A (EA), an active component of HE, with special focus on the GLT-1 function in the in vitro and in vivo cerebral ischemia mouse models. By using oxygen-glucose deprivation (OGD) to challenge mouse glia-neuron (GN) mixed culture as the in vitro model, we found that EA treatment significantly improved neuronal/astroglial survival and attenuated OGD-induced proinflammatory NFκB and AKT signaling activations. Notably, EA attenuated OGD-induced GLT-1 downregulation, and a selective GLT-1 inhibitor WAY-213613 reversed these EA-mediated neuroprotection. EA also ameliorated glutamate excitotoxicity effectively. In a transient hypoxia-ischemia (tHI) brain injury mouse model, we examined an EA treatment strategy by performing a pre-tHI daily oral gavage of EA (oEA) for 7 days followed by a post-tHI intranasal injection of EA (nEA) for 3 days, and found that this treatment significantly protected sensorimotor cortex and improved the post-tHI forepaw grip strength. Western blotting results further revealed that EA treatment also preserved astrocyte-enriched glutamate and aspartate transporter (GLAST) as well as a GLT-1 function-associated potassium channel Kir4.1 in the cerebral cortex and striatum after tHI. These results suggest that EA is effective for preserving GLT-1 and glutamate clearance machinery to protect against excitotoxicity after ischemic brain injury.

Hericium erinaceus (HE) is a common edible mushroom consumed in several Asian countries and considered to be a medicinal mushroom with neuroprotective effects. Erinacine A (EA) is a bioactive compound in Hericium erinaceus mycelium (HEM) that has been shown to have a neuroprotective effect against neurodegenerative diseases, e.g., Parkinson's disease (PD). Although the etiology of PD is still unclear, neuroinflammation may play an important role in causing dopaminergic neuron loss, which is a pathological hallmark of PD. However, glial cell activation has a close relationship with neuroinflammation. Thus, this study aimed to investigate the anti-neuroinflammatory and neuroprotective effects of EA on lipopolysaccharide (LPS)-induced glial cell activation and neural damage in vitro and in vivo. For the in vitro experiments, glial cells, BV-2 microglial cells and CTX TNA2 astrocytes were pretreated with EA and then stimulated with LPS and/or IFN-γ. The expression of proinflammatory factors in the cells and culture medium was analyzed. In addition, differentiated neuro-2a (N2a) cells were pretreated with EA or HEM and then stimulated with LPS-treated BV-2 conditioned medium (CM). The cell viability and the amount of tyrosine hydroxylase (TH) and mitogen-activated protein kinases (MAPKs) were analyzed. In vivo, rats were given EA or HEM by oral gavage prior to injection of LPS into the substantia nigra (SN). Motor coordination of the rats and the expression of proinflammatory mediators in the midbrain were analyzed. EA pretreatment prevented LPS-induced iNOS expression and NO production in BV-2 cells and TNF-α expression in CTX TNA2 cells. In addition, both EA and HEM pretreatment significantly increased cell viability and TH expression and suppressed the phosphorylation of JNK and NF- κB in differentiated N2a cells treated with CM. In vivo, both EA and HEM significantly improved motor dysfunction in the rotarod test and the amphetamine-induced rotation test and reduced the expression of TNF-α, IL-1β and iNOS in the midbrain of rats intranigrally injected with LPS. The results demonstrate that EA ameliorates LPS-induced neuroinflammation and has neuroprotective properties.