Antiinflamatory effect of materials based on gold and silver nanoparticles and Sambucus Nigra L. on carrageenan- induced rat paw edema Adriana Filip a, Doina Daicoviciu a, Nicoleta Decea a, Pompei Bolfa b, Simona Clichici a, Adriana Muresan a, Luminita David c, Liliana Olenic d a Department of Physiology, „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; b Department of Morphopathology, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania; c Faculty of Chemistry and Chemical Engineering, Babes-Bolyai – University, Cluj-Napoca, Romania; d National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania 22nd EADV, October 2-6, 2013 Istanbul, Turkey This work was elaborated in the frame project no 147/2012, through the program “Partnerships in priority areas-PN II”

Introduction  The biological synthesis of silver and gold nanoparticles using plants or fruits extracts plays an important role in the field of nanotechnology and nanomedicine as it offers alternative therapeutic options which are safe, free of side effects and effective for a variety of diseases.  Inflammation is a complex biological response involved in pathogenesis of various diseases.  Although steroids and NSAIDs are the main therapeutic agents used in the treatment of inflammation they cause serious side effects. Therefore, the development of new materials with comparable results and no side effects is needed.  Aim to investigate the biological activity of materials based on gold (Au-SN) and silver (Ag-SN) nanoparticles and natural compounds extracted from European black elderberry - Sambucus nigra L., (SN) on acute inflammation model in Wistar rats.

Materials and Methods  the inflammation was induced by intraplantar injection of 100 μl 1% carrageenan  SN extract (15 mg/kg b.w.) and the materials based on gold (Au-SN) and silver (Ag-SN) nanoparticles functionalized with SN extract (0.3 mg/kg b.w.) were administrated orally during 4 days before the injection of carageenan  the response was compared to indomethacin (5 mg/b.w.) as positive control and saline solution as negative control.  at 2h, 24h and 48h after carageenan injection were evaluated:  the paw edema  the immunohistochemical expression of iNOS and COX-2 in the paw tissue  the malondialdehyde (MDA), glutathione reduced/glutathione oxidized ratio (GSH/GSSG), IL-1α, IL-1β and IL-6 levels in soft plantar tissue  Comparisons were made by one-way ANOVA, with Tukey multiple comparisons test using a GraphPad Prism software program, version 5.0 (GraphPad, San Diego, Ca, USA).  p<0,05 was considered as significant.

Malondialdehyde level (a), GSH/GSSG ratio (b) and paw edema (c) in soft tissue at 2h, 24h and 48h after carrageenan injection a b c

Proinflammatory cytokines levels in soft plantar tissue at 2h, 24h and 48h after carrageenan injection in animals pretreated with materials based on gold and silver nanoparticles and natural extracts iNOS 2h COX-2, 2h COX-2, 24hiNOS, 24h

Conclusions  SN significantly inhibited edema formation and MDA generation in carrageenan-induced paw edema model, particularly at 2h.  Silver nanoparticles functionalized with SN extract increased GSH/GSSG ratio at 48h after induction of inflammation.  Both SN extract and silver nanopartciles based on SN diminished IL-1α, IL-1β and IL-6 levels and reduced iNOS and COX-2 expressions at 2h after carrageean injection.  These findings suggested that both silver nanoparticles functionalized with SN as well as SN extract may be useful agents in the treatment of inflammatory conditions. HE, 48h COX-2, 48hiNOS 48h