Eze Fredrick Nwude, Bunyapongpan Apinna, Prapunpoj Porntip
Drug Delivery System Excellence Center, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
Heliyon. 2024 Oct 9;10(20):e39159. doi: 10.1016/j.heliyon.2024.e39159. eCollection 2024 Oct 30.
Transthyretin (ATTR) amyloidosis is a progressive and life-threatening neurodegenerative disease caused by aggregation of the plasma transport protein, transthyretin, for which treatment is rare and cure unavailable. is a small edible herb with a long history of neurological application in ethnomedicine. This work investigated whether hydrophilic extract of (CAB) could suppress the toxic effects of transthyretin amyloid aggregate (TTRa) in cell model derived from the same target. TTRa was prepared via thermal-induced aggregation. Chemical cross-linking and Tricine-SDS-PAGE, Thioflavin-T fluorescence, and TEM analyses confirmed that TTRa matched the profile of TTRL55P nonfibrillar amyloid aggregates. PrestoBlue cell viability assay revealed that exposure of IMR-32 human neuroblastoma cells to TTRa (2-8 μM) resulted in significant cytotoxicity. Conversely, exposure of IMR-32 cells to CAB did not adversely affect their viability. In addition, when IMR-32 cells were co-treated with TTRa and varied concentrations of CAB, the toxic effect of TTRa was significantly (p < 0.01) inhibited dose-dependently. The extract was found to possess potent radical scavenging effects, and quantitative RP-HPLC analysis showed that asiaticoside and phenolics were its main components. The cytoprotective effect against TTRa, antioxidant property, and good safety profile collectively suggest that CAB could be applied in the development of nutraceuticals or therapeutics against transthyretin amyloidosis.
转甲状腺素蛋白（ATTR）淀粉样变性是一种由血浆转运蛋白转甲状腺素蛋白聚集引起的进行性且危及生命的神经退行性疾病，针对该疾病的治疗方法罕见且无法治愈。[此处原文缺失植物名称]是一种可食用的小草本植物，在民族医学中有着悠久的神经学应用历史。这项研究调查了[此处原文缺失植物名称]的亲水性提取物（CAB）是否能在源自相同[此处原文缺失相关靶点]的细胞模型中抑制转甲状腺素蛋白淀粉样聚集体（TTRa）的毒性作用。TTRa通过热诱导聚集制备。化学交联、Tricine - SDS - PAGE、硫黄素 - T荧光和透射电镜分析证实TTRa符合TTRL55P非纤维状淀粉样聚集体的特征。PrestoBlue细胞活力测定显示，将IMR - 32人神经母细胞瘤细胞暴露于TTRa（2 - 8μM）会导致显著的细胞毒性。相反，将IMR - 32细胞暴露于CAB对其活力没有不利影响。此外，当IMR - 32细胞与TTRa和不同浓度的CAB共同处理时，TTRa的毒性作用被显著（p < 0.01）剂量依赖性抑制。发现该提取物具有强大的自由基清除作用，定量RP - HPLC分析表明积雪草苷和酚类是其主要成分。对TTRa的细胞保护作用、抗氧化特性以及良好的安全性表明，CAB可用于开发针对转甲状腺素蛋白淀粉样变性的营养保健品或治疗药物。
