Alteration of Lipid Bilayer Electrical Potential by Phytochemicals and Synthetic Analogs: Implications for Cellular Function

Phytochemicals, including flavonoids, stilbenoids, alkaloids, terpenoids, and structurally related synthetic small molecules, exhibit a broad spectrum of beneficial pharmacological effects. These effects stem not only from interactions with specific protein targets but also from their capacity to modify the physical properties of biological membranes. A key membrane property influenced by these plant-derived compounds is the electrical potential drop at the membrane-water interface, which plays a crucial role in numerous cellular processes. Changes in membrane potential impact the function of embedded proteins and ion channels, thereby modulating cell signaling, transport, and pharmacological responses. This review compiles data on how diverse plant and synthetic small molecules alter membrane physical characteristics, particularly the dipole component of the boundary potential in lipid bilayers primarily composed of phosphatidylcholine, a predominant membrane lipid in mammals and fungi. In-depth analysis of structure-activity relationships in this context elucidates how various structural modifications affect the compounds' ability to shift membrane electrical potential. Understanding these relationships can pinpoint molecular features that drive membrane interactions and facilitate the discovery and design of more potent dipole-modifying agents with therapeutic potential.