pH and Charge Effects Behind the Interaction of Artepillin C, the Major Component of Green Propolis, With Amphiphilic Aggregates: Optical Absorption and Fluorescence Spectroscopy Studies

Abstract

Brazilian green propolis is one of the bee products most consumed in the world to prevent diseases, owing antioxidant, antimicrobial, anti‐inflammatory and antitumor activities. The major component of Brazilian green propolis is Artepillin C (ArtC), a cinnamic acid derivative with two prenylated groups that improve the affinity of the compound for lipophilic environment. Here, we have employed optical absorption and fluorescence techniques to draw conclusions on how ArtC interacts with amphiphilic aggregates commonly used as model membranes having different charges in the polar head group. Optical absorption spectra were representative of the protonation state of ArtC, dictated by the local pH at the surface of micelles and lipid vesicles. Fluorescence results showed that, in the presence of micelles and vesicles, the polarizability around ArtC was modified, compared to the value in aqueous medium, and the molecule should be located preferentially on the surface region of the model membranes, with an enhanced interaction with the less ordered state of the lipid vesicles.

pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells

“…The literature supports the notion that Artepillin C favors a neutral state as pH decreases [17]. Beyond 50 µM, molecules tend to aggregate due to their limited water solubility, augmenting interactions with lipophilic domains, such as the cell plasma membrane, and subsequently intensifying cytotoxic effects [18,22,34]. Notably, the decline in cellular viability observed at pH values of 6.8, 6.5, and 6.0 when cells were exposed to Artepillin C concentrations exceeding 50 µM, marked by significant differentiation from the respective pH controls, clearly underscores the pH-dependent effect.…”

“…Interestingly, this metabolic shift persists regardless of molecular oxygen levels in cancer cells, leading to a substantial elevation in lactate production-up to 40 times higher compared to healthy cells [21]. A previous study showed that models mimicking healthy and tumor cell membranes exhibit distinct responses based on lipid composition and media pH [18,22]. Under physiological conditions (pH 7.4), Artepillin C exhibits an affinity for the lipid assembly without perturbing the structural integrity of the lipid membrane.…”

“…The core structure primarily comprises a phenolic acid, wherein the carboxyl moiety's deprotonation is contingent upon the surrounding pH. Notably, the reported pKa value of Artepillin C is 4.65, with its lipophilicity varying in correspondence to its protonation state [17,18]. Within this context, it is pertinent to underscore the acidic attributes of the extracellular microenvironment in tumor cells.…”

Spectral Photoluminescent Parameters of Barley Seeds (Hordéum vulgáre) Infected with Fusarium ssp

“…The optical absorption spectra represented the state of protonation dictated by the local pH on the surface of micelles and lipid vesicles (20). Useful data were obtained for the optimization of postharvest photochemical protocols for the valorization of cabbage waste using a nondestructive optical sensor (21).…”