Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress

Fundam Clin Pharmacol. 2014 Aug;28(4):455-64. doi: 10.1111/fcp.12049. Epub 2013 Sep 17.

Abstract

Studies have shown that diterpenes have anti-inflammatory and redox-protective pharmacological activities. The present study aimed to investigate the anti-inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti-inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ-carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2 ]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan-induced paw edema, in a dose-dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80-, histamine-, serotonin-, bradykinin- and PGE2 -induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels, and MDA concentration; and increased GSH levels during carrageenan-induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL-1β and TNF-α levels and oxidative stress.

Keywords: anti-inflammatory; cytokine; oxidative stress; phytol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Edema / drug therapy
  • Edema / pathology
  • Glutathione / metabolism
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Interleukin-1beta / metabolism
  • Leukocytes / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Neutrophils / metabolism
  • Oxidative Stress / drug effects*
  • Peroxidase / metabolism
  • Phytol / administration & dosage
  • Phytol / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Phytol
  • Malondialdehyde
  • Peroxidase
  • Glutathione