Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation

Pharm Res. 2009 Jan;26(1):224-31. doi: 10.1007/s11095-008-9734-9. Epub 2008 Oct 8.

Abstract

Purpose: Accumulating evidence from epidemiologic and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. Curcumin (CUR) has been strongly linked to the anti-inflammatory effect. On the other hand, isothiocyanates such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) are strong phase-II detoxifying/antioxidant enzymes inducer. Therefore it is interesting to see if combination of these drugs can inhibit inflammation with higher combined efficacies.

Methods: We used nitric oxide (NO) assay to assess the synergism of the different combinations of CUR, SFN and PEITC. The inflammatory markers, e.g. iNOS, COX-2, prostaglandin E2 (PGE2), tumor necrosis factor (TNF) and interleukin-1 (IL-1) levels were determined using RT-PCR, Western blot and ELISA assays.

Results: We report that combination of PEITC + SFN or CUR + SFN has a synergistic effect in down-regulating inflammation markers like TNF, IL-1, NO, PGE2. The synergism is probably due to the synergistic induction of phase II/antioxidant enzymes including heme-oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1).

Conclusions: Our data suggest that CUR + SFN and PEITC + SFN combinations could be more effective than used alone in preventing inflammation and possibly its associated diseases including cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal*
  • Anticarcinogenic Agents / pharmacology*
  • Biomarkers
  • Cell Line
  • Curcumin / pharmacology*
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Synergism
  • Interleukin-1 / metabolism
  • Isothiocyanates / pharmacology*
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiocyanates / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Biomarkers
  • Interleukin-1
  • Isothiocyanates
  • Lipopolysaccharides
  • Thiocyanates
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • phenethyl isothiocyanate
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • sulforafan
  • Curcumin
  • Dinoprostone