Planta Med 2011; 77(17): 1890-1897
DOI: 10.1055/s-0031-1280022
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Hydroxytyrosol Is the Major Anti-Inflammatory Compound in Aqueous Olive Extracts and Impairs Cytokine and Chemokine Production in Macrophages

Nathalie Richard1 , Sabine Arnold1 , Ulrich Hoeller1 , Claus Kilpert1 , Karin Wertz1 , Joseph Schwager1
  • 1DSM Nutritional Products Ltd., Department of Human Nutrition & Health, Basel, Switzerland
Further Information

Publication History

received February 25, 2011 revised May 26, 2011

accepted May 31, 2011

Publication Date:
09 August 2011 (online)


Substances in olive products contribute to improved health as suggested by epidemiological data. In this study we assessed the effects of hydroxytyrosol (HT) on inflammatory mediators, cytokines and chemokines, and identified anti-inflammatory constituents of aqueous olive extracts, i.e., olive vegetation water (OVW). Murine macrophages (RAW264.7 cells) were stimulated with lipopolysaccharide (LPS) in the absence or presence of substances; inflammatory mediators [nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, interleukins, chemokines] were determined by the Griess reaction, EIA, or multiplex ELISA (Luminex technology). Expression of inflammatory genes was determined by RT-PCR. Aqueous olive extracts were fractionated by preparative HPLC and the fractions investigated for their effects on NO and PGE2 production. Results were further analyzed by principal component analysis. HT inhibited production of NO and PGE2 with an IC50 of 11.4 and 19.5 µM, respectively, reflecting strong anti-inflammatory activity. HT and OVW diminished secretion of cytokines (IL-1α, IL-1β, IL-6, IL-12, TNF-α), and chemokines (CXCL10/IP-10, CCL2/MCP-1). HT and OVW concentration-dependently reduced the expression of genes of inducible nitric oxide synthase (iNOS), IL-1α, CXCL10/IP-10, MIP-1β, matrix metalloproteinase-9, and prostaglandin E2 synthase (PGES). The effects of HT were partly mediated via the NF-κB pathway, as shown by RT-PCR analysis. HT was identified as the main bioactive compound of OVW. The data provide a molecular basis for elucidating the effects of HT on inflammatory processes. The effects of HT on NO and chemokine production point to their impact on chronic inflammatory processes in endothelium or arthritis.

Supporting Information


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Dr. Joseph Schwager

Department of Human Nutrition & Health
DSM Nutritional Products Ltd

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