Antinociceptive and Anti-Inflammatory Activity of Bovine Milk-Derived -Lactoglobulin: Study of Combined Effect with Tramadol or Indomethacin

4 Abstract: Considerable efforts and resources have been dedicating to the development of anti-inflammatory products; of particular interest are functional foods capable of modulating the expression of this activity. -lactoglobulin ( -lag) is the major whey protein of ruminant species and is also present in the milks of many, but not all, other species. This study was designed to evaluate the analgesic and the anti-inflammatory effects of -lactoglobulin. The antinociceptive effect of Tramadol and -lag was evaluated either alone or in combination using the hot plate method. Mice received Tramadol alone (20 mg/kg, i.p.), -lag alone (150, 300 mg/kg, orally), or in combination. The combined treatment was divided into two phases; phase 1(5-60min), showed significant antinociception of combined treatment compared to Tramadol alone. In phase 2 (120-180min.), the antinociceptive effect decreased with time suggesting that combined treatments resulted in synergistic effect in phase 1 and antagonism in phase 2. Carrageenan-induced paw edema was used to investigate the anti-inflammatory activity of -lag. -lag alone (150, 300 mg/kg, orally) or combined with Indomethacin (5 mg/kg orally) reduced paw edema, decreased the production of serum PGE2, TNF- and IL-1 and brain MDA, while it increased brain SOD and TAC. Normal prothrombin time was recorded in -lag treatment alone while indomethacin decreased prothrombin time. -lag treatment showed almost normal mucosal layer in histopathological examination of the gastric mucosa compared to indomethacin. -lag appears to possess anti-inflammatory and peripheral antinociceptive activities, so it may be a candidate for nutraceutical ingredient.