Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
Biomed Pharmacother. 2018 Jan;97:1-8. doi: 10.1016/j.biopha.2017.09.130. Epub 2017 Nov 6.
Peumus boldus (P. boldus) is a medicinal plant popularly used in the treatment of gastrointestinal disorders. P. boldus aqueous extract is rich in phenolic compounds and alkaloids that possess antiinflammatory and antioxidant effects. In the present study, the potential protective effect of P. boldus against Cu-induced toxicity was investigated. Adult Drosophila melanogaster were exposed to Cu (1mM and 3mM) and/or P. boldus aqueous extract (5mg/mL) in the food during 4days. Cu-fed flies had impairment in the negative geotaxis performance (i.e. motor climbing capability) as well as a higher incidence of mortality when compared to the control group. P. boldus co-treatment afforded protection against the Cu-induced toxicity. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activity decreased significantly in D. melanogaster after Cu exposure. P. boldus co-exposure for 4days restored enzyme activities to control levels. In addition, Cu exposure caused a significant increase in the mRNA levels of antioxidant enzymes, superoxide dismutase (Sod1), catalase (Cat), thioredoxin reductase (TrxR1) and nuclear factor erythroid 2-related factor 2 (Nrf2), as well as increased the mRNA levels of acetylcholinesterase (Ace). The expression of P-type ATPase (Atp7A) and copper uptake protein 1 (Ctr1A) mRNAs were up-regulated in D. melanogaster exposed to Cu. The co-treatment with P. boldus blunted Cu-induced up-regulation of Atp7A and down-regulated Ctr1A mRNA expression. These findings suggest that P. boldus extracts reduce Cu-induced toxicity but not Cu absorption in D. melanogaster. Consequently, P. boldus can be a potential therapeutical alternative for modulating Cu-associated toxicity.
狭叶南洋杉（P. boldus）是一种药用植物，常用于治疗胃肠道疾病。狭叶南洋杉的水提物富含具有抗炎和抗氧化作用的酚类化合物和生物碱。在本研究中，研究了狭叶南洋杉对铜诱导毒性的潜在保护作用。成年黑腹果蝇在 4 天的食物中暴露于铜（1mM 和 3mM）和/或狭叶南洋杉水提物（5mg/mL）。与对照组相比，喂食铜的果蝇在负趋地性表现（即运动攀爬能力）上受损，死亡率更高。狭叶南洋杉的共同处理提供了对铜诱导毒性的保护。乙酰胆碱酯酶（AChE）和谷胱甘肽 S-转移酶（GST）活性在黑腹果蝇暴露于铜后显著降低。狭叶南洋杉共同暴露 4 天可将酶活性恢复至对照水平。此外，铜暴露导致抗氧化酶超氧化物歧化酶（Sod1）、过氧化氢酶（Cat）、硫氧还蛋白还原酶（TrxR1）和核因子红细胞 2 相关因子 2（Nrf2）的 mRNA 水平显著增加，以及乙酰胆碱酯酶（Ace）的 mRNA 水平增加。暴露于铜的黑腹果蝇中 P 型 ATP 酶（Atp7A）和铜摄取蛋白 1（Ctr1A）mRNA 的表达上调。狭叶南洋杉的共同处理减弱了铜诱导的 Atp7A 上调和 Ctr1A mRNA 表达下调。这些发现表明，狭叶南洋杉提取物可降低铜诱导的毒性，但不能降低铜在黑腹果蝇中的吸收。因此，狭叶南洋杉可以作为一种潜在的治疗选择，用于调节铜相关毒性。
