113 Encapsulated Activated-Grape Seed Extract (ACTIVITIS™) inhibits demethylation of PP2A promoting anti-aging benefits and barrier repair for human skin

Abstract

Cumulative oxidative stress and chronic inflammation are critical during skin aging. One pathway that regulates both processes involves Protein phosphatase 2A (PP2A), a serine/threonine phosphatase. Reversible methylation of the C-terminal leucine of the PP2A catalytic subunit (PP2Ac) plays a crucial role in regulating PP2A function. Oxidative stress has been previously shown to dramatically decrease methylation of the C-terminal leucine of the PP2A catalytic subunit (PP2Ac) in dermal fibroblasts. Previously, we developed a novel, proprietary grape seed extract called Activated-Grape Seed Extract, or ACTIVITIS™ (INCI name: anthocyanins and hydrolyzed proanthocyanidins) which is enriched for PP2A-activating flavonoids with increased potency in preventing PP2A demethylation when compared to commercial Grape Seed Extract. To enhance skin delivery and other potential benefits of ACTIVITIS™, we developed a chemical encapsulation formulation utilizing a liposome-based approach. Results demonstrate that this novel encapsulated form of ACTIVITIS™ retains PP2A demethylating activity with similar potency as the non-encapsulated form. To explore the potential benefits of encapsulated ACTIVITIS™, we performed in vitro assays utilizing 3D epidermal skin tissue models and UVB irradiation. We found encapsulated ACTIVITIS™ significantly increases both cell proliferation (Ki67) and skin barrier (Filaggrin) marker expression after UVB irradiation. Moreover, encapsulated ACTIVITIS™ formulation decreases DNA damage marker Cyclobutane pyrimidine dimers (CPD), thus enhancing epidermal integrity and barrier repair after UVB-induced effects. Lastly, clinical results in human subjects demonstrates that encapsulated ACTIVITIS™ is well tolerated and provides anti-aging benefits such as improving fine lines and wrinkles when applied topically.