Novel Functions of Bovine Milk-Derived α-Lactalbumin: Anti-nociceptive and Anti-inflammatory Activity Caused by Inhibiting Cyclooxygenase-2 and Phospholipase A2

Milk whey proteins contain major components of alpha-lactalbumin (alpha LA) and beta-lactoglobulin (beta LG), and a minor component of lactoferrin (LF). It has been reported that LF reduces nociception and inflammation in various animal models. However, the efficacy of alpha LA and beta LG has not been clarified. This study aimed to assess the efficacy of alpha LA and beta LG in various animal models such as acetic acid-induced writhing, carrageenan-induced paw inflammation, and adjuvant induced-arthritis. Orally administered alpha LA showed (i) inhibition of writhing induced by acetic acid in mice; (ii) suppression of nociception and inflammation in rat footpads caused by carrageenan in rat; and (iii) therapeutic effects on the development of adjuvant-induced pain and inflammation in rat. In contrast, beta LG had no effects in these animal models. To clarify the anti-nociceptive and anti-inflammatory mechanisms of alpha LA, we examined the levels of interleukin (IL)-6 and prostaglandin (PG)E-2 in carrageenan-injected paw exudates. The administration of alpha LA 1 h before carrageenan injection inhibited the increased formation of IL-6 and PGE(2) in paw exudates. Next, we demonstrated in vitro enzyme-inhibition assay; cyclooxygenase (COX), phospholipase A(2), and 5-lipoxygenase. alpha LA inhibited COX and phospholipase A(2) activities. alpha LA inhibited COX and phospholipase A(2) activities. Moreover, alpha LA showed selectivity on COX-2 as compared with COX-1. However, 5-lipoxygenase activity was not affected by alpha LA. These results suggest that alpha LA is a safe and useful natural drug for patients that require anti-inflammatory drugs, as alpha LA is contained in dairy food and is frequently ingested as daily food.