Antioxidant-mediated protective role of Hericium erinaceus (Bull.: Fr.) Pers. against oxidative damage in fibroblasts from Friedreich’s ataxia patient

Abstract

Friedreich's ataxia (FRDA) is a progressive neuromuscular disorder caused by substantial decrease of mitochondrial protein frataxin responsible for biogenesis of iron-sulphur clusters and protection from oxidative damage. On this study, we investigated the antioxidant activities of a standardized aqueous extract from fruiting bodies of Hericium erinaceus mushroom (HESAE) and its protective effects against oxidative damage induced by L-Buthionine sulfoximine (BSD) in fibroblasts derived from FRDA patient. The lactate dehydrogenase-based viability assay showed that FRDA fibroblast was sensitive to 12.5 mM BSD with a reduction of viability to 52.51 ± 13.92% after 24 h of BSD exposure. Onterestingly, co-incubation with 32 mg/mL HESAE increased the viability to 85.35 ± 3.4%. Further, 12.5 mM BSD caused a decrease in the ratio of cellular reduced glutathione (GSH) to oxidised GSH (GSSG) that leads to cell death. Nevertheless, the damage was reduced by co-incubation with 32 mg/mL HESAE. Nuclear fluorescence staining revealed that 12.5 mM BSD induced cell death and the apoptosis was decreased by co-incubation with HESAE. These findings suggest the ability of HESAE in attenuating BSD-mediated cytotoxicity through maintenance of membrane integrity and optimal GSH/GSSG ratio, that are closely linked to its antioxidant activities. Further in vivo trials are highly warranted to clarify its potential benefits in management of FRDA.

Hericium erinaceus potentially rescues behavioural motor deficits through ERK-CREB-PSD95 neuroprotective mechanisms in rat model of 3-acetylpyridine-induced cerebellar ataxia

“…Phenolic acids of H. erinaceus that possess hydroxyl groups have been shown to exert antioxidant properties by counteracting oxidative stress and other detrimental changes in brain tissues. Our findings that H. erinaceus has enhanced neuroplasticity functions were in agreement with previous studies on the neuritogenic and nerve regeneration effects of H. erinaceus 16 , 20 , 37 , 74 – 77 .…”

“…The aqueous extract of H. erinaceus used in this study has been standardised to contain 20.66% beta 1,3–1,6 glucan and 0.17% adenosine 37 , and these compounds have been shown to play pivotal roles in neuroprotection and neuroplasticity-related functions 56 , 57 . In this study, we focused primarily on the neuroplasticity-related mechanisms of ERK-CREB-PSD95 (Fig.…”

“…To our knowledge, there are no reports of natural products that possess neuroprotective effects on acquired cerebellar ataxia, and this prompted us to examine the neuroprotective effects of H. erinaceus and to investigate its mechanisms in a neurodegenerative disorder model. Substantial evidence indicates that intrinsic free radical scavenging contributes to the neuroprotective effects of H. erinaceus 37 . Phenolic acids of H. erinaceus that possess hydroxyl groups have been shown to exert antioxidant properties by counteracting oxidative stress and other detrimental changes in brain tissues.…”

“…erinacines A-G) that can pass through the blood brain barrier and stimulate NGF synthesis [28][29][30][31] . Of particular interest, the standardised aqueous extract of H. erinaceus used in the present study contains 20.66% beta-glucan and 0.17% adenosine 37 . Betaglucan derived from Lentinus edodes or Shiitake mushroom known as lentinan has been demonstrated to induce long-term potentiation in the rat dentate gyrus, indicating the potential effect of beta-glucan on neuroplasticity Figure 6.…”

“…Total glucan and α-glucan were determined by the β-glucan assay kit (Megazyme International, Wicklow, Ireland). Adenosine content was analysed and quantified by high-performance liquid chromatography (HPLC) using in house method (Nova Laboratories Private Limited, Sepang, Selangor, Malaysia) 37 .…”