Effects of salvianolic acid A on β-amyloid mediated toxicity in Caenorhabditis elegans model of Alzheimer's disease
Keywords:
Salvianolic acid A, Alzheimer’s disease, β-amyloid, C. elegansAbstract
Alzheimer’s disease (AD) is a brain disease attributed to the accumulation of extracellular senile plaques comprising β-amyloid peptide (Aβ). In this study, a transgenic Caenorhabditis elegans (C. elegans) containing the human beta amyloid Aβ42 gene which exhibited paralysis when expressed, was used to study the anti-paralysis effect of salvianolic acid A. Various concentrations ranging from 1 μg/ml to 100 μg/ml of salvianolic acid A were tested which exhibited the highest effect on the worm at the concentration of 100 μg/ml. For anti-aggregation effect, 14 μg/ml of salvianolic acid A (within 4 mg/ml of Danshen) showed a significant level of inhibition of the formation of Aβ fibrils. An amount of 100 μg/ml of salvianolic acid A had the potential in reducing the reactive oxygen species (ROS) but did not totally obliterate the ROS production in the worms. Salvianolic acid A was found to delay the paralysis of the transgenic C. elegans, decrease Aβ42 aggregation and decrease Aβ-induced oxidative stress.
References
Walsh, D.M. and D.B. Teplow, Alzheimer's disease and the amyloid β-protein, in Progress in molecular biology and translational science. 2012, Elsevier. p. 101-124.
Glenner, G.G. and C.W. Wong, Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochemical and biophysical research communications, 1984. 122(3): p. 1131-1135.
Kang, J., et al., The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 1987. 325(6106): p. 733.
Goate, A., et al., Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 1991. 349(6311): p. 704.
Hardy, J.A. and G.A. Higgins, Alzheimer's disease: the amyloid cascade hypothesis. Science, 1992. 256(5054): p. 184-186.
Jia, Q., Y. Deng, and H. Qing, Potential therapeutic strategies for Alzheimer’s disease targeting or beyond β-amyloid: insights from clinical trials. BioMed research international, 2014. 2014.
Xu, J.-z., et al., Simultaneous detection of seven phenolic acids in Danshen injection using HPLC with ultraviolet detector. Journal of Zhejiang University SCIENCE B, 2008. 9(9): p. 728-733.
Lin, T.-J., K.-J. Zhang, and G.-T. Liu, Effects of salvianolic acid A on oxygen radicals released by rat neutrophils and on neutrophil function. Biochemical pharmacology, 1996. 51(9): p. 1237-1241.
Zhang, H., et al., Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling. Free Radical Biology and Medicine, 2014. 69: p. 219-228.
Yan, X., Dan Shen (Salvia miltiorrhiza) in Medicine. 2015: Springer.
McColl, G., et al., Utility of an improved model of amyloid-beta (Aβ 1-42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer’s disease. Molecular neurodegeneration, 2012. 7(1): p. 57.
Gutierrez-Zepeda, A., et al., Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans. BMC neuroscience, 2005. 6(1): p. 54.
Sola, I., et al., Multigram synthesis and in vivo efficacy studies of a novel multitarget anti-Alzheimer’s compound. Molecules, 2015. 20(3): p. 4492-4515.
Bharadwaj, P.R., et al., Aβ aggregation and possible implications in Alzheimer's disease pathogenesis. Journal of cellular and molecular medicine, 2009. 13(3): p. 412-421.
DaSilva, K.A., J.E. Shaw, and J. McLaurin, Amyloid-β fibrillogenesis: structural insight and therapeutic intervention. Experimental neurology, 2010. 223(2): p. 311-321.
Lorenzo, A. and B. Yankner, Amyloid Fibril Toxicity in Alzheimer's Disease and Diabetes a. Annals of the New York Academy of Sciences, 1996. 777(1): p. 89-95.
Azriel, R. and E. Gazit, Analysis of the minimal amyloid-forming fragment of the islet amyloid polypeptide an experimental support for the key role of the phenylalanine residue in amyloid formation. Journal of Biological Chemistry, 2001. 276(36): p. 34156-34161.
Makin, O.S., et al., Molecular basis for amyloid fibril formation and stability. Proceedings of the National Academy of Sciences, 2005. 102(2): p. 315-320.
Porat, Y., A. Abramowitz, and E. Gazit, Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chemical biology & drug design, 2006. 67(1): p. 27-37.
Link, C.D., C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer’s disease. Experimental gerontology, 2006. 41(10): p. 1007-1013.
Link, C.D., et al., Visualization of fibrillar amyloid deposits in living, transgenic Caenorhabditis elegans animals using the sensitive amyloid dye, X-34. Neurobiology of aging, 2001. 22(2): p. 217-226.
Link, C.D., et al., Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer’s disease model. Neurobiology of aging, 2003. 24(3): p. 397-413.
Drake, J., C.D. Link, and D.A. Butterfield, Oxidative stress precedes fibrillar deposition of Alzheimer’s disease amyloid β-peptide (1–42) in a transgenic Caenorhabditis elegans model. Neurobiology of aging, 2003. 24(3): p. 415-420.
Yin, F., et al., Baicalin prevents the production of hydrogen peroxide and oxidative stress induced by Aβ aggregation in SH-SY5Y cells. Neuroscience letters, 2011. 492(2): p. 76-79.
Bastianetto, S., S. Krantic, and R. Quirion, Polyphenols as potential inhibitors of amyloid aggregation and toxicity: possible significance to Alzheimer's disease. Mini reviews in medicinal chemistry, 2008. 8(5): p. 429-435.
Cao, Y.Y., et al., Salvianolic acid A, a polyphenolic derivative from Salvia miltiorrhiza bunge, as a multifunctional agent for the treatment of Alzheimer’s disease. Molecular diversity, 2013. 17(3): p. 515-524.
Back, P., B.P. Braeckman, and F. Matthijssens, ROS in aging Caenorhabditis elegans: damage or signaling? Oxidative medicine and cellular longevity, 2012. 2012.
Yanase, S. and N. Ishii, Cloning of the oxidative stress-responsive genes in Caenorhabditis elegans. Journal of radiation research, 1999. 40(1): p. 39-47.
Rangsinth, P., et al., Leaf extract of Caesalpinia mimosoides enhances oxidative stress resistance and prolongs lifespan in Caenorhabditis elegans. BMC complementary and alternative medicine, 2019. 19(1): p. 164.
Tsai, M.-K., Y.-L. Lin, and Y.-T. Huang, Effects of salvianolic acids on oxidative stress and hepatic fibrosis in rats. Toxicology and applied pharmacology, 2010. 242(2): p. 155-164.
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