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Protective Effect and Mechanism of Fruit Extract of Aegle marmelos Against Amyloid-β Toxicity in a Transgenic Caenorhabditis elegans
Natural Product Communications ( IF 1.5 ) Pub Date : 2020-07-17 , DOI: 10.1177/1934578x20933511
Roongpetch Keowkase 1 , Nattanon Kijmankongkul 1 , Wanapong Sangtian 1 , Sireethorn Poomborplab 1 , Chatpiti Santa-ardharnpreecha 1 , Natthida Weerapreeyakul 2, 3 , Worapan Sitthithaworn 4
Affiliation  

Alzheimer’s disease (AD) is the most common form of dementia found in the elderly. AD is caused by the accumulation of toxic proteins including amyloid-β (Aβ). The purpose of this study was to investigate the effect of fruit extract of Aegle marmelos against Aβ toxicity in Caenorhabditis elegans. The fruit of A. marmelos has been used in a traditional Thai herb formula in fatigue patients recovering from illnesses such as fever and diarrhea. We used a transgenic C. elegans strain CL4176, which expresses the human Aβ42, to investigate the effects and the mechanisms of action of the extracts against Aβ toxicity. The extract of A. marmelos significantly delayed Aβ-induced paralysis. Aegle marmelos lost the ability to delay Aβ-induced paralysis in worms fed with daf-16 ribonucleic acid interference (RNAi) bacteria, but not in worms fed with hsf-1 and skin-1 RNAi bacteria. These results indicated that daf-16 transcription factor was required for A. marmelos-mediated delayed paralysis. Aegle marmelos enhanced the level of daf-16 gene. Taken together, these results indicated that A. marmelos reduced Aβ toxicity via the DAF-16-mediated cell signaling pathway. In addition, A. marmelos reduced toxic Aβ oligomers. Aegle marmelos also displayed antioxidative effect in in vivo as it enhanced resistance to paraquat-induced oxidative stress in wild type worms. All of the results suggested that A. marmelos can protect against Aβ-induced toxicity and can be a potential candidate for the prevention or treatment of AD.



中文翻译:

棉花糖果实提取物对转基因秀丽隐杆线虫β淀粉样蛋白毒性的保护作用及其机制

阿尔茨海默氏病(AD)是老年人中最常见的痴呆形式。AD是由包括淀粉样蛋白-β(Aβ)在内的毒性蛋白的积累引起的。这项研究的目的是研究淡色桃的水果提取物对秀丽隐杆线虫的Aβ毒性的影响。A. marmelos的果实已被用于传统的泰国草药配方中,使疲倦的患者从发烧和腹泻等疾病中恢复过来。我们使用表达人Aβ42的转基因秀丽隐杆线虫菌株CL4176来研究提取物抗Aβ毒性的作用和作用机理。A. marmelos的提取物显着延迟了Aβ诱导的麻痹。饲喂daf-16核糖核酸干扰(RNAi)细菌的蠕虫中的Aegle marmelos丧失了延迟Aβ诱导的麻痹的能力,但饲喂hsf-1skin-1 RNAi细菌的蠕虫中却没有这种能力。这些结果表明,daf-16转录因子是A.marmelos介导的延迟性麻痹所必需的。Aegle marmelos提高了daf-16基因的水平。综上所述,这些结果表明,marmelos通过DAF-16介导的细胞信号传导途径降低了Aβ毒性。此外,A。marmelos还原了有毒的Aβ低聚物。伊格玛洛斯在体内也显示出抗氧化作用,因为它增强了野生型蠕虫对百草枯引起的氧化应激的抵抗力。所有结果表明,A。marmelos可以预防Aβ诱导的毒性,并且可以作为预防或治疗AD的潜在候选药物。

更新日期:2020-07-17
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