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. In 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 (BSO) in fibroblasts derived from FRDA patient. The lactate dehydrogenase-based viability assay showed that FRDA fibroblast was sensitive to 12.5 mM BSO with a reduction of viability to 52.51 ± 13.92% after 24 h of BSO exposure. Interestingly, co-incubation with 32 mg/mL HESAE increased the viability to 85.35 ± 3.4%. Further, 12.5 mM BSO 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 BSO induced cell death and the apoptosis was decreased by co-incubation with HESAE. These findings suggest the ability of HESAE in attenuating BSO-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.

摘要 弗里德赖希共济失调（Friedreich’s ataxia, FRDA）是一种进行性神经肌肉疾病，由负责铁硫簇（iron-sulphur clusters）生物合成与抗氧化损伤的线粒体蛋白frataxin显著减少所引发。本研究探究了猴头菇（Hericium erinaceus）子实体标准化水提取物（HESAE）的抗氧化活性，及其对L-丁硫氨酸-亚砜亚胺（L-Buthionine sulfoximine, BSO）诱导的FRDA患者来源成纤维细胞氧化损伤的保护作用。乳酸脱氢酶法活力检测结果显示，FRDA成纤维细胞对12.5 mM BSO敏感，经BSO处理24小时后细胞活力降至52.51 ± 13.92%。值得注意的是，与32 mg/mL HESAE共孵育可将细胞活力提升至85.35 ± 3.4%。此外，12.5 mM BSO会降低细胞内还原型谷胱甘肽（reduced glutathione, GSH）与氧化型谷胱甘肽（oxidised GSH, GSSG）的比值，进而引发细胞死亡；但与32 mg/mL HESAE共孵育可缓解该损伤。核荧光染色结果表明，12.5 mM BSO可诱导细胞死亡，而HESAE共孵育可降低细胞凋亡率。上述研究结果表明，HESAE可通过维持细胞膜完整性与最优GSH/GSSG比值，减轻BSO介导的细胞毒性，这一作用与其抗氧化活性密切相关。后续需开展进一步体内试验，以明确其在FRDA管理中的潜在益处。