title: The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis.
abstract: OBJECTIVE
  To investigate the effects of the naturally occurring stilbenoid pinosylvin on neutrophil activity in vitro and in experimental arthritis, and to examine whether protein kinase C (PKC) activation served as an assumed target of pinosylvin action.
  
  
  METHODS
  Fresh human blood neutrophils were isolated. The oxidative burst of neutrophils was evaluated on the basis of enhanced chemiluminescence. Neutrophil viability was evaluated with flow cytometry, and PKC phosphorylation was assessed by Western blotting analysis. Adjuvant arthritis was induced in Lewis rats with heat-killed Mycobacterium butyricum, and the animals were administered with pinosylvin (30 mg/kg, po) daily for 21 d after arthritis induction.
  
  
  RESULTS
  In isolated human neutrophils, pinosylvin (10 and 100 μmol/L) significantly decreased the formation of oxidants, both extra- and intracellularly, and effectively inhibited PKC activation stimulated by phorbol myristate acetate (0.05 μmol/L). The inhibition was not due to neutrophil damage or increased apoptosis. In arthritic rats, the number of neutrophils in blood was dramatically increased, and whole blood chemiluminescence (spontaneous and PMA-stimulated) was markedly enhanced. Pinosylvin administration decreased the number of neutrophils (from 69 671 ± 5588/μL to 51 293 ± 3947/μL, P=0.0198) and significantly reduced the amount of reactive oxygen species in blood.
  
  
  CONCLUSIONS
  Pinosylvin is an effective inhibitor of neutrophil activity, and is potentially useful as a complementary medicine in states associated with persistent inflammation.
authors: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic. viera.jancinova@savba.sk
authors: Viera
authors: V
authors: Jančinová
authors: Tomáš
authors: T
authors: Perečko
authors: Rado
authors: R
authors: Nosáľ
authors: Juraj
authors: J
authors: Harmatha
authors: Jan
authors: J
authors: Smidrkal
authors: Katarína
authors: K
authors: Drábiková
mesh_terms: D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D041605:Pinus sylvestris / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult; D000094162:Phytoalexins
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011493:Protein Kinase C; D017382:Reactive Oxygen Species; D013267:Stilbenes; C049032:pinosylvin; D000094162:Phytoalexins