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

Authors

  • 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

Abstract

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-silico experiments, 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.

Downloads

Download data is not yet available.

References

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

with neurological 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 of computation 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.

Journal of Graphic Era University

Vol. 6, Issue 2, 270-281, 2018

ISSN: 0975-1416 (Print), 2456-4281 (Online)

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,

(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

Downloads

Published

2023-02-28

How to Cite

Anthwal, P., Sati, B. K., Thapliyal, M., Verma, D., Kumar, N., & Thapliyal, A. (2023). Role of Fatty Acids/Fat Soluble Component from Medicinal Plants Targeting BACE Modulation and Their Role in Onset of AD: An in-silico Approach. Journal of Graphic Era University, 6(2), 270–281. Retrieved from https://www.journal.riverpublishers.com/index.php/JGEU/article/view/83

Issue

Section

Articles