Immunomodulatory Activity of Electrospun Polyhydroxyalkanoate Fiber Scaffolds Incorporating Olive Leaf Extract

Jose Gustavo De La Ossa,Giovanna Donnarumma,Karen De Clerck,Ipsita Roy,Marco Macchia,Alessandra Fusco,Serena Danti,Rossella Di Stefano,Andrea Lazzeri,Bahareh Azimi,Maria Digiacomo,Maria-Beatrice Coltelli,Jasmine Esposito Salsano

doi:10.3390/app11094006

Abstract

Olive tree is a well-known source of polyphenols. We prepared an olive leaf extract (OLE) and characterized it via high performance liquid chromatography (HPLC) analysis. OLE was blended with different polyhydroxyalkanoates (PHAs), namely, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) and polyhydroxybutyrate/poly(hydroxyoctanoate-co-hydroxydecanoate) (PHB/PHOHD), to produce fiber meshes via electrospinning: OLE/PHBV and OLE/ (PHB/PHOHD), respectively. An 80–90% (w/w%) release of the main polyphenols from the OLE/PHA fibers occurred in 24 h, with a burst release in the first 30 min. OLE and the produced fiber meshes were assayed using human dermal keratinocytes (HaCaT cells) to evaluate the expression of a panel of cytokines involved in the inflammatory process and innate immune response, such as the antimicrobial peptide human beta defensin 2 (HBD-2). Fibers containing OLE were able to decrease the expression of the pro-inflammatory cytokines at 6 h up to 24 h. All the PHA fibers allowed an early downregulation of the pro-inflammatory cytokines in 6 h, which is suggestive of a strong anti-inflammatory activity exerted by PHA fibers. Differently from pure OLE, PHB/PHOHD fibers (both with and without OLE) upregulated the expression of HBD-2. Our results showed that PHA fiber meshes are suitable in decreasing pro-inflammatory cytokines and the incorporation of OLE may enable indirect antibacterial properties, which is essential in wound healing and tissue regeneration.

Highlights

Olive tree (i.e., Olea europaea) is one of the most ancient trees of the Mediterranean area.By virtue of its properties, olive tree derivatives have been employed in traditional medicine as botanical drugs and food supplements
high performance liquid chromatography (HPLC) analysis allowed to determine the main phenolic compounds present in olive leaf extract (OLE), which were oleuropein and luteolin-7-O-glucoside, with a concentration of 32.64 ± 3.06 mg/g of OLE and 6.97 ± 0.24 mg/g of OLE, respectively
In a similar fashion to the findings reported for the other cytokines, all the PHA fibers downregulated the expression of TNF-α independently of OLE incorporation

Summary

Introduction

By virtue of its properties, olive tree derivatives have been employed in traditional medicine as botanical drugs and food supplements. Olive leaf extract (OLE) has been considered for different purposes [1], for example, as an antihypertensive, antiatherogenic, anti-inflammatory, hypoglycemic or hypocholesterolemic agent [2,3,4]. The secoiridoid oleuropein is the main component of OLE, in addition to other secoiridoids derived from tyrosol structures and flavonoids. The nutraceutical properties of OLE have been attributed to secoiridoid oleuropein and its derivatives, such as hydroxytyrosol [7]. Polyphenol concentration in OLE may depend on the geographical position, type of cultivar, age of the olive tree and collection season [8,9]

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