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