Role of Fatty Acids/Fat Soluble Component from Medicinal Plants Targeting BACE Modulation and Their Role in Onset of AD: An in-silico Approach
Keywords:
Fatty Acids, PUFA, Alzheimer’s disease, BACE, Amyloid beta, phyto constituents, Lipinski’s rulesAbstract
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.
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