title: Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress.
abstract: BACKGROUND
  Gum of Chios mastic (Pistacia lentiscus var. chia) is a natural antimicrobial agent that has found extensive use in pharmaceutical products and as a nutritional supplement. The molecular mechanisms of its anti-inflammatory activity, however, are not clear. In this work, the potential role of antioxidant activity of Chios mastic gum has been evaluated.
  
  
  METHODS
  Scavenging of superoxide radical was investigated by electron spin resonance and spin trapping technique using EMPO spin trap in xanthine oxidase system. Superoxide production in endothelial and smooth muscle cells stimulated with TNF-α or angiotensin II and treated with vehicle (DMSO) or mastic gum (0.1-10 μg/ml) was measured by DHE and HPLC. Cellular H2O2 was measured by Amplex Red. Inhibition of protein kinase C (PKC) with mastic gum was determined by the decrease of purified PKC activity, by inhibition of PKC activity in cellular homogenate and by attenuation of superoxide production in cells treated with PKC activator phorbol 12-myristate 13-acetate (PMA).
  
  
  RESULTS
  Spin trapping study did not show significant scavenging of superoxide by mastic gum itself. However, mastic gum inhibited cellular production of superoxide and H2O2 in dose dependent manner in TNF-α treated rat aortic smooth muscle cells but did not affect unstimulated cells. TNF-α significantly increased the cellular superoxide production by NADPH oxidase, while mastic gum completely abolished this stimulation. Mastic gum inhibited the activity of purified PKC, decreased PKC activity in cell homogenate, and attenuated superoxide production in cells stimulated with PKC activator PMA and PKC-dependent angiotensin II in endothelial cells.
  
  
  CONCLUSIONS
  We suggest that mastic gum inhibits PKC which attenuates production of superoxide and H2O2 by NADPH oxidases. This antioxidant property may have direct implication to the anti-inflammatory activity of the Chios mastic gum.
authors.affiliation: Medical School of Athens, Athens, Greece.
authors.forename: Angelike
authors.initials: A
authors.lastname: Triantafyllou
authors.forename: Alfiya
authors.initials: A
authors.lastname: Bikineyeva
authors.forename: Anna
authors.initials: A
authors.lastname: Dikalova
authors.forename: Rafal
authors.initials: R
authors.lastname: Nazarewicz
authors.forename: Stamatios
authors.initials: S
authors.lastname: Lerakis
authors.forename: Sergey
authors.initials: S
authors.lastname: Dikalov
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D042783:Endothelial Cells / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D000069997:Mastic Resin; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D027927:Pistacia / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012116:Resins, Plant / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D000069997:Mastic Resin; D010936:Plant Extracts; D012116:Resins, Plant; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000804:Angiotensin II; C016658:phorbolol myristate acetate; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate