An Anti-microbial Terpenoid Fraction from Gymnema sylvestre Induces Flip-flop of Fluorescent-Phospholipid Analogs in Model Membrane

Therapeutic potential of Gymnema sylvestre on diverse cell types is predominantly due to a variety of terpenoids and their derivatives. However, their bioavailability becomes limited due to poor solubility and lower lipophilic properties, provoking the search for novel membranotropic terpenoids and...

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Bibliographic Details
Published in:Applied biochemistry and biotechnology 2020-12, Vol.192 (4), p.1331-1345
Main Authors: Behuria, Himadri Gourav, Sahu, Santosh Kumar
Format: Article
Language:English
Subjects:
Analogs
Anti-Infective Agents - pharmacology
Antiinfectives and antibacterials
Antimicrobial activity
Bioavailability
Biochemistry
Biotechnology
Chemistry
Chemistry and Materials Science
Fluorescence
Fluorescent Dyes - chemistry
Gram-negative bacteria
Gymnema sylvestre
Gymnema sylvestre - chemistry
Hydrophobic and Hydrophilic Interactions
Linear phase
Lipid bilayers
Lipid Bilayers - chemistry
Lipids
Lipophilic
Lipophilicity
Membranes
Membranes, Artificial
Microorganisms
Phospholipids
Phospholipids - chemistry
Terpenes
Terpenes - pharmacology
Translocation
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Summary:Therapeutic potential of Gymnema sylvestre on diverse cell types is predominantly due to a variety of terpenoids and their derivatives. However, their bioavailability becomes limited due to poor solubility and lower lipophilic properties, provoking the search for novel membranotropic terpenoids and their mechanism of action. A terpenoid fraction purified from Gymnema sylvestre exhibited broad spectrum antimicrobial activity against both Gram positive and Gram negative bacteria with IC 50 ˂ 0.1 mg/ml. Evaluation of its membranotropic effect in vitro on reconstituted model membrane revealed that the fraction induced flip-flop of fluorescent phospholipid analogs across the lipid bilayer. The terpenoid-induced lipid flipping was biphasic with a fast linear phase (rate constant ( k 1 ) = 3 to 5 S −1 ) and a second slow exponential phase (rate constant ( k 2 ) = (4 to 9) × 10 −3  S −1 ). The lipid-flippase activity of the terpenoid fraction showed concentration and incubation-dependent cooperativity, indicating their lipophilic nature and membrane-destabilizing activity that facilitated lipid translocation. For the first time, our study reveals the flippase activity of a terpenoid fraction of Gymnema sylvestre that could be further explored for their membrane-mediated pharmacological properties. Graphical Abstract
ISSN:0273-2289
1559-0291
DOI:10.1007/s12010-020-03399-3