Effects of Ellagic Acid on Vaginal Innate Immune Mediators and HPV16 Infection In Vitro

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-08, Vol.29 (15), p.3630
• Main Authors: Promsong, Aornrutai, Chuerduangphui, Jureeporn, Levy, Claire N, Hladik, Florian, Satthakarn, Surada, Nittayananta, Wipawee
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Antimicrobial agents; Bacteria; beta-Defensins - metabolism; Biotechnology industry; Cell culture; Cervical cancer; Chemokines; Cytokines; Cytokines - metabolism; Cytotoxicity; Ellagic acid; Ellagic Acid - pharmacology; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - virology; Experiments; Female; Fungi; hBD2; Health aspects; HEK293 Cells; HIV; HPV-16; Human immunodeficiency virus; Human papillomavirus; Human papillomavirus 16; Humans; Immunity, Innate - drug effects; Infection; Infections; innate immune factors; Papillomavirus infections; Papillomavirus Infections - drug therapy; Papillomavirus Infections - immunology; Papillomavirus Infections - virology; Pathogens; Peptides; phenolic phytochemical; Proteins; Resveratrol; Vagina; Vagina - drug effects; Vagina - immunology; Vagina - virology; Viruses; Womens health
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29153630

Ellagic acid (EA) is a phenolic phytochemical found in many plants and their fruits. Vaginal epithelial cells are the first line of defense against pathogen invasion in the female reproductive tract and express antimicrobial peptides, including hBD2 and SLPI. This study investigated the in vitro effects of EA (1) on vaginal innate immunity using human vaginal epithelial cells, and (2) on HPV16 pseudovirus infection. Vaginal cells were cultured in the presence or absence of EA, and the expression of hBD2 and SLPI was determined at both transcriptional and translational levels. In addition, secretion of various cytokines and chemokines was measured. Cytotoxicity of EA was determined by CellTiter-blue and MTT assays. To investigate the ability of EA to inhibit HPV16 infection, EA was used to treat HEK-293FT cells in pre-attachment and adsorption steps. We found significant increases in both mRNA (mean 2.9-fold at 12.5 µM EA, < 0.001) and protein (mean 7.1-fold at 12.5 µM EA, = 0.002) in response to EA. mRNA also increased significantly (mean 1.4-fold at 25 µM EA, = 0.01), but SLPI protein did not. Secretion of IL-2 but not of other cytokines/chemokines was induced by EA in a dose-dependent manner. EA was not cytotoxic. At the pre-attachment step, EA at CC and CC showed a slight trend towards inhibiting HPV16 pseudovirus, but this was not significant. In summary, vaginal epithelial cells can respond to EA by producing innate immune factors, and at tested concentrations, EA is not cytotoxic. Thus, plant-derived EA could be useful as an immunomodulatory agent to improve vaginal health.