Role of Fatty Acids/Fat Soluble Component from Medicinal Plants Targeting BACE Modulation and Their Role in Onset of AD: An in-silico Approach

  • Prashant Anthwal Department of Life Sciences and Biotechnology, Graphic Era Deemed to be University, Dehradun, India
  • Bipin Kumar Sati Department of Life Sciences and Biotechnology, Graphic Era Deemed to be University, Dehradun, India
  • Madhu Thapliyal Department of Zoology, Government Degree College, Raipur, Dehradun
  • Devvret Verma Department of Life Sciences and Biotechnology, Graphic Era Deemed to be University, Dehradun, India
  • Navin Kumar Department of Life Sciences and Biotechnology, Graphic Era Deemed to be University, Dehradun, India
  • Ashish Thapliyal Department of Life Sciences and Biotechnology, Graphic Era Deemed to be University, Dehradun, India
Keywords: Fatty Acids, PUFA, Alzheimer’s disease, BACE, Amyloid beta,, phyto constituents, Lipinski’s rules


Fatty acids have been reported in several researches targeting cure and treatment of Alzheimer’s disease(AD). Besides having so many contradictory reports about fatty acids related to the issues of human health, there are many evidences that point towards the beneficial effects of PUFAs and essential fatty acids on human health, even in AD. This study investigated the interaction of fatty acids and phyto-constituents for the inhibition of BACE enzyme (mainly responsible and prominent target for amyloid hypothesis) through in-silico approach. Phyto-compounds from Picrorhiza kurroa, Cinnamomum tamala, Curcuma longa, Datura metel, Rheum emodi and Bacopa monnieri, which are well known, were screened. For screening of drug molecules, Lipinski’s rule is usually used. Because of this rule compounds like Bacoside A, Bacoside A3, Bacopaside II, Bacopasaponin C, Baimantuoluoline C, Daturameteline A, Cucurbitacin B, Cucurbitacin D, Cucurbitacin E, Cucurbitacin I, Cucurbitacin F, Cucurbitacin R, Picroside III, Kutkoside, Picroside II are usually excluded from docking/binding studies because of their higher molecular weight as they do now follow the Lipinski’s rules.The same applies to fatty acids, like Linolinic acid. On the basis of in-silicoexperiments, our study suggests that certain polyunsaturated fatty acids (PUFA) and some saturated fatty acids of medicinal plants can have BACE inhibition activity and can possibly modulate Aβ formation.Our study also suggests that compounds that are excluded by Lipinski’s rule/filter during bioinformatics based screening due to their molecular weight should also be tested in experiments as we hypothesize that Lipinski’s rule is not absolute.


Download data is not yet available.


Amen, D. G., Harris, W. S., Kidd, P. M., Meysami, S., & Raji, C. A. (2017). Quantitative erythrocyte omega-3 EPA plus DHA levels are related to higher regional cerebral blood flow on brain SPECT. Journal of Alzheimer's Disease, 58(4), 1189-1199.

Babel, O. (2011). An open chemical toolbox O'Boyle Noel M; Banck Michael; James Craig A; Morley Chris; Vandermeersch Tim; Hutchison Geoffrey R. Journal of Cheminformatics, 3, 33.

Bazinet, R. P., & Layé, S. (2014). Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Reviews Neuroscience, 15(12), 771-785.

Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: few candidates, freqHsu et al., 2011uent failures. Alzheimer's Research & Therapy, 6(4), 37.

Cunnane, S. C., Schneider, J. A., Tangney, C., Tremblay-Mercier, J., Fortier, M., Bennett, D. A., & Morris, M. C. (2012). Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. Journal of Alzheimer's Disease, 29(3), 691-697.

Farooqui, A. A. (2009). Lipid mediators in the neural cell nucleus: their metabolism, signaling, and association withneurological disorders. The Neuroscientist, 15(4), 392-407.

Farooqui, A. A., Horrocks, L. A., & Farooqui, T. (2007). Modulation of inflammation in brain: a matter of fat. Journal of Neurochemistry, 101(3), 577-599.

Haag, M. (2003). Essential fatty acids and the brain. The Canadian Journal of Psychiatry, 48(3), 195-203.

Hsu, K. C., Chen, Y. F., Lin, S. R., & Yang, J. M. (2011). iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinformatics, 12(1), S33.

Jicha, G. A., & Markesbery, W. R. (2010). Omega-3 fatty acids: potential role in the management of early Alzheimer's disease. Clinical Investigations in Aging. 5, 45-61.

Jorgensen, W. L. (2004). The many roles ofcomputation in drug discovery. Science, 303(5665), 1813-1818.

Kapoor, T., Semwal, P., Anthwal, P., Thapliyal, M., & Thapliyal, A. (2013). Quercetin, bergapten and barberineb as analogues of rifampicin and isoniazid screened in silico from herbal plants of Uttarakhand for the treatment of tuberculosis (TB). Biotech International, 6(4), 48-57.

Nasaruddin, M. L., Hölscher, C., Kehoe, P., Graham, S. F., & Green, B. D. (2016). Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer’s disease as detected by GC-MS. American Journal of Translational Research, 8(1), 154.

Semwal, P., Tripathi, R., & Thapliyal, A. (2015). Herbal active components act as inhibitor against HCV NS3/4A protease by using bioinformatics approach. Drug Discovery, 10(23), 15-21.

Snowden, S. G., Ebshiana, A. A., Hye, A., An, Y., Pletnikova, O., O’Brien, R., & Thambisetty, M. (2017). Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study. PLoS medicine, 14(3), e1002266.

Tan, Z. S., Harris, W. S., Beiser, A. S., Au, R., Himali, J. J., Debette, S., & Robins, S. J. (2012). Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology, 78(9), 658-664.

Torres, M., Price, S. L., Fiol-deRoque, M. A., Marcilla-Etxenike, A., Ahyayauch, H., Barceló-Coblijn, G., . & Ibarguren, M. (2014). Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimer's disease. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1838(6), 1680-1692.

Yang, X., Sun, G. Y., Eckert, G. P., & Lee, J. C. (2014). Cellular membrane fluidity in amyloid precursor protein processing. Molecular Neurobiology, 50(1), 119-129.

Yehuda, S., Rabinovitz, S., Carasso, R. L., & Mostofsky, D. I. (2002). The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiology of Aging, 23(5), 843-853.