title: Anti-inflammatory activity of Punica granatum L. (Pomegranate) rind extracts applied topically to ex vivo skin.
abstract: Coadministered pomegranate rind extract (PRE) and zinc (II) produces a potent virucidal activity against Herpes simplex virus (HSV); however, HSV infections are also associated with localised inflammation and pain. Here, the objective was to determine the anti-inflammatory activity and relative depth penetration of PRE, total pomegranate tannins (TPT) and zinc (II) in skin, ex vivo. PRE, TPT and ZnSO4were dosed onto freshly excised ex vivo porcine skin mounted in Franz diffusion cells and analysed for COX-2, as a marker for modulation of the arachidonic acid inflammation pathway, by Western blotting and immunohistochemistry. Tape stripping was carried out to construct relative depth profiles. Topical application of PRE to ex vivo skin downregulated expression of COX-2, which was significant after just 6h, and maintained for up to 24h. This was achieved with intact stratum corneum, proving that punicalagin penetrated skin, further supported by the depth profiling data. When PRE and ZnSO4were applied together, statistically equal downregulation of COX-2 was observed when compared to the application of PRE alone; no effect followed the application of ZnSO4alone. TPT downregulated COX-2 less than PRE, indicating that tannins alone may not be entirely responsible for the anti-inflammatory activity of PRE. Punicalagin was found throughout the skin, in particular the lower regions, indicating appendageal delivery as a significant route to the viable epidermis. Topical application of TPT and PRE had significant anti-inflammatory effects in ex vivo skin, confirming that PRE penetrates the skin and modulates COX-2 regulation in the viable epidermis. Pomegranates have potential as a novel approach in ameliorating the inflammation and pain associated with a range of skin conditions, including cold sores and herpetic stromal keratitis.
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, Wales, United Kingdom; Department of Microbiology & Infectious Diseases, School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales, United Kingdom.
authors.forename: David M J
authors.initials: DM
authors.lastname: Houston
authors.affiliation: Department of Microbiology & Infectious Diseases, School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales, United Kingdom; Institute of Microbiology, Armed Forces Medical Academy, Neuherbergstraβe 11, 80937 München, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Bugert
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, Wales, United Kingdom; University of Brighton, Mithras House, Lewes Road, Brighton BN2 4AT, United Kingdom.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Denyer
authors.affiliation: School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, Wales, United Kingdom. Electronic address: heard@cardiff.ac.uk.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D029561:Lythraceae / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013552:Swine; D015032:Zinc / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000893:Anti-Inflammatory Agents; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; C115642:punicalagin; D051546:Cyclooxygenase 2; D015032:Zinc
keywords: Anti-inflammation; COX-2; Ex vivo; Pomegranate; Punica granatum; Skin; Tannins; Tape stripping