摘要
研究灯盏细辛总咖啡酰奎宁酸(caffeoylquinic acid from Erigeron breviscapus,EBCQA)的抗衰老作用,并探讨其潜在作用机制.以线虫为模型,观察EBCQA对其寿命、氧化抗性、热抗性、运动能力、DAF-16入核、以及超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)活性和丙二醛(malondialdehyde,MDA)含量的影响.腹腔注射D-半乳糖构建衰老大鼠模型,检测EBCQA对大鼠学习记忆能力、胸腺和脾脏系数、肝脏中磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)、蛋白激酶B(Akt/protein kinase B,Akt)、磷酸化 Akt(phosphp-Akt,p-Akt)、叉头框蛋白 O3a(forkhead box class O3a,FOXO3a)、磷酸化 FOXO3a(phosphp-FOXO3a,p-FOXO3a)表达,以及肝脏和血清中SOD、GSH-Px、CAT活性和MDA含量的影响.结果显示,EB-CQA能够延长野生型线虫寿命,并提升其氧化抗性、热抗性和运动能力,但对线虫PI3K、Akt、FoxO3a同源体突变株寿命没有显著影响;EBCQA能促进DAF-16入核,通过DAF-16提升线虫的SOD、GSH-Px、CAT活性,降低MDA水平.在D-半乳糖诱导衰老大鼠中,EBCQA给药显著改善大鼠的学习记忆功能,提升胸腺和脾脏系数,降低PI3K、Akt、p-Akt、p-FoxO3a表达和MDA含量,增强SOD、GSH-Px、CAT活性.以上结果表明,EBCQA具有延缓衰老的作用,其机制可能与抑制PI3K和Akt激活、降低FOXO3a磷酸化、促进FOXO3a入核和转录活性、提升抗氧化酶活性和抑制氧化应激相关.
Abstract
To investigate the anti-aging effect of caffeoylquinic acid from Erigeron breviscapus(EBCQA),and explore its un-derlying mechanism of action.Caenorhabditis elegans(C.elegans)was used as a model to investigate the impact of EBCQA on its lifespan,oxidative and thermal resistance,motility,nuclear translocation of DAF-16,enzyme activities of superoxide dis-mutase(SOD),glutathione peroxidase(GSH-Px),catalase(CAT),and malondialdehyde(MDA)content.The aging rat model was established by intraperitoneal injection of D-galactose,and the effects of EBCQA on its learning and memory abili-ty,thymus and spleen coefficients,the expression of phosphoinositide 3-kinase(PI3K),Akt/protein kinase B(Akt),phos-php-Akt(p-Akt),forkhead box class O3a(FOXO3a)and phosphp-FOXO3a(p-FOXO3a)in liver,the enzyme activities of SOD,GSH-Px,CAT,and MDA content in liver and serum were assessed.The results showed that EBCQA was able to extend lifespan of wild-type nematodes,enhance oxidative resistance,thermal resistance,and motility,but it has no significant effects on the lifespan of mutant strains of nematode orthologs of PI3K,Akt,and FoxO3a.Furthermore,EBCQA could promote DAF-16 nuclear translocation,elevate the SOD,GSH-Px,CAT activities and decrease MDA levels in a DAF-16 dependent manner.In D-galactose-induced aging rat,the administration of EBCQA notably improved the learning and memory function,increased thymus and spleen coefficients,reduced the protein expression of PI3K,Akt,p-Akt,p-FoxO3a and MDA content,enhanced SOD,GSH-Px,CAT activities.The above results indicate that EBCQA has an anti-aging effect and the mechanism may be at-tributed to its potential inhibition of PI3K and Akt activation,reduction of FOXO3a phosphorylation,promotion of FOXO3a nuclear translocation and transcriptional activity,enhancement of antioxidant enzyme activity,and inhibition of oxidative stress.
基金项目
云南省科技厅基础研究专项面上项目(202201AT070213)
云南省科技厅基础研究专项面上项目(202401AT070146)
云南省科技厅中医联合专项面上项目(2019FF002-049)
云南省科技厅中医联合专项面上项目(202301AZ070001-054)
维普
万方数据