Alaskan Berry Extracts Promote Dermal Wound Repair Through Modulation of Bioenergetics and Integrin Signaling

• Published in: Frontiers in Pharmacology
• Main Authors: Esposito, Debora, Overall, John, Grace, Mary H., Komarnytsky, Slavko, Lila, Mary Ann
• Format: Text
• Language: English
• Published: Frontiers Media S.A. 2019
• Subjects: Pharmacology; Arctic; Crowberry; Empetrum nigrum; Alaska
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776586/; http://www.ncbi.nlm.nih.gov/pubmed/31611784; https://doi.org/10.3389/fphar.2019.01058

Various wild berry species endemic to Alaska and the circumpolar North that exhibit unique medicinal properties have long been appreciated by indigenous Arctic communities. Traditional use of Alaskan berry preparations in the treatment of skin wounds is recorded but has not been scientifically evaluated. Alaskan wild berries feature diverse phytochemical compositions that contain a variety of bioactive polyphenols exhibiting anti-inflammatory, antioxidant, and antimicrobial properties, making them ideal for wound healing interventions and natural anti-aging cosmeceutical formulations. Given increasing interest in identifying biologically active plant constituents for wound care and cosmeceutical applications, the objective of this study was to screen several wild berry species endemic to Alaska and the circumpolar Artic for wound healing and in the crude, polyphenol-enriched, and further fractionated extracts of: Empetrum nigrum (crowberry), Vaccinium uliginosum (bog blueberry), and V. vitis-idaea (low-bush cranberry or lingonberry). A cell migration assay with human dermal fibroblasts (HDFa) was performed to model promotion of wound closure, revealing that bog blueberry extract most actively promoted migration, whereas divergent effects observed with other berry extracts were related to compositional disparities. Lipopolysaccharide (LPS)-stimulated inflammatory response variables measured in RAW 264.7 macrophages [reactive oxygen species (ROS), NO production, prostaglandin-endoperoxide synthase 2 (COX-2), and inducible nitric oxide synthase (iNOS) expression] were suppressed by most extracts/fractions, but especially bog blueberry and proanthocyanidin (PAC) fractions. Wild berry germplasm contained abundant complex flavonoid structures such as PAC and anthocyanins (ANCs), associated with enhanced repair and inflammatory resolution in these models. Next, underlying mechanisms by which PACs and bioactive metabolites (B2 dimer and epicatechin) could influence wound repair and tissue regeneration were examined. PAC ...