天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (增刊2): 33-39.

• 研究论文 • 上一篇    下一篇

车叶草苷抗BJ细胞衰老的活性及分子对接研究

汤   建1，洪   庆2，李艳玲1，赵康琦1，闻崇炜2*   

  1. 1亳州学院中药学院，亳州 236800；2江苏大学药学院，镇江 212013
  • 出版日期:2022-12-07 发布日期:2022-12-07
  • 基金资助:
    安徽省高等学校自然科学研究项目（KJ2019ZD80）；安徽省亳州市第四批产业创新团队建设项目（BZI-4002）；亳州学院科研项目（BYZ2018B02）；亳州学院科研启动基金（BZQD201901）

Anti-aging effect of asperuloside on BJ cells and molecular docking study

TANG Jian1,HONG Qing2,LI Yan-ling1,ZHAO Kang-qi1,WEN Chong-wei2*   

  1. 1School of Chinese Medicine,Bozhou University,Bozhou 236800,China;2School of Pharmacy,Jiangsu University,Zhenjiang 212013,China
  • Online:2022-12-07 Published:2022-12-07

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摘要：

车叶草苷（asperuloside，ASP）是一种环烯醚萜化合物，为研究其抗衰老潜力，本文中采用人成纤维BJ细胞模型评价其保护活性，采用端粒酶重复片段扩增实验（telomeric repeat amplification protocol，TRAP）测试其对端粒酶的激活作用。并进一步采用AutoDock Vina软件与96种衰老相关蛋白进行分子对接，虚拟筛选该化合物可能的靶点蛋白，预测其活性机制。发现车叶草苷在较低浓度（0.01和0.1 μmol/L）时可以提高倍增次数（population doubling，PD）27的BJ细胞存活率，对34 PD BJ细胞表现出更加明显的促生长作用，且对34 PD BJ细胞中端粒酶具有明显的激活作用。分子对接结果显示，车叶草苷与Kelch样ECH关联蛋白1（ECH-associated protein 1，KEAP1）、沉默信息调节因子1（silent information regulator 1，SIRT1）、多聚ADP核糖聚合酶1（poly (ADP-ribose) polymerase 1，PARP1）等19种靶点蛋白的结合能超过-33.5 kJ/mol，其中与KEAP1、SIRT1的结合能最高，分别为-38.5、38.1 kJ/mol。对哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）也具有较强的结合能力。这意味着车叶草苷可能通过KEAP1/NRF2、SIRT1、mTOR通路等机制发挥端粒酶激活和抗衰老作用。

关键词: 车叶草苷, 抗衰老, BJ细胞, 端粒酶, 分子对接

Abstract:

Asperuloside (ASP),an iridoid glycoside,was studied to evaluate its anti-aging effect by detecting the cell viability in human fibroblast BJ cells,followed by a telomeric repeat amplification protocol (TRAP) for analyzing telomerase activity.AutoDock Vina was used to dock asperuloside with 96 selected proteins,to virtually determine the potential anti-aging target,and predict its mechanism.The pretreatment of BJ cell with asperuloside at lower concentrations (0.01 and 0.1 μmol/L) increased viability of 27 population doubling (PD) BJ cells,and it was more active for 34 PD BJ cells.Asperuloside stimulated the telomerase activity in 34 PD BJ cells.Asperuloside had higher than -33.5 kJ/mol binding affinity with 19 proteins including ECH-associated protein 1 (KEAP1),silent information regulator 1 (SIRT1),poly (ADP-ribose) polymerase 1 (PARP1) and so on.Among them,the highest scores of -38.5 and -38.1 kJ/mol were found in docking with KEAP1 and SIRT1.Docked with mammalian target of rapamycin (mTOR),asperuloside also had higner affinity score.These suggested that asperuloside might be a potential stimulating telomerase and anti-aging resource,associated with KEAP1/NRF2,SIRT1,mTOR pathway and so on.

Key words: asperuloside, anti-aging, BJ cell, telomerase, molecular docking

中图分类号:  R93

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