Anti-amyloidogenic and anti-apoptotic effect of alpha-bisabolol against A beta induced neurotoxicity in PC12 cells

作者：Shanmuganathan Balakrishnan; Suryanarayanan Venkatesan; Sathya Sethuraman; Narenkumar Muralidharan; Singh Sanjeev Kumar; Ruckmani Kandasamy; Devi Kasi Pandima^*

来源：European Journal of Medicinal Chemistry, 2018, 143: 1196-1207.

DOI：10.1016/j.ejmech.2017.10.017

• Anti-amyloidogenic
• Anti-apoptotic
• A beta(25-35) peptide
• alpha-bisabolol
• PC12 cells

Alzheimer's disease (AD) is a life-threatening neurodegenerative disorder leading to dementia, with a progressive decline in memory and other thinking skills of elderly populace. Of the multiple etiological factors of AD, the accumulation of senile plaques (SPs) particularly as A beta oligomers correlates with the relentlessness cognitive impairment in AD patients and play a vital role in AD pathology. Since natural essential oil constituents have successfully served as a source of drugs for AD treatment, the present study aims at the in vitro and in silico investigation of anti-amyloidogenic potential and anti-apoptotic property of the alpha-bisabolol against A beta(25-35) induced neurotoxicity in PC12 cells. Treatment with alpha-bisabolol (5 mu g/ml) after 24 h incubation with A beta(25-35) reduced the aggregation propensity of A beta (p < 0.05), as observed by the reduced fluorescence intensity of thioflavin T (ThT). Confocal laser scanning microscopy (CLSM) analysis, Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopic analysis and molecular dynamics simulation study also substantiated the A beta fibril formation hampering ability of alpha-bisabolol even after 9 days of incubations. The results of antiaggregation and disaggregation assay showed an increase in fluorescence intensity in A beta treated group, whereas the co-treatment of alpha-bisabolol (5 mu g/ml) with A beta(25-35) showed an extensive decrease in the fluorescence intensity, which suggests that alpha-bisabolol prevents the oligomers formation as well as disaggregates the matured fibrils. FACS analysis of the cells revealed the competency of alpha-bisabolol in rescuing the PC12 cells from A beta induced neurotoxicity and chromosomal damage and clonogenic assay proved its ability to retain the colony survival of cells. Overall, the anti-amyloidogenic and anti-apoptotic effect of alpha-bisabolol proves that it could be used as an excellent therapeutic drug to combat AD.

• 出版日期2018-1-1
• 单位北京理工大学