Novel functions of bovine milk-derived α-lactalbumin: Anti-nociceptive and anti-inflammatory activity caused by inhibiting cyclooxygenase-2 and phospholipase A2

Abstract

Milk whey proteins contain major components of α-lactalbumin (αLA) and β-lactoglobulin (βLG), 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 αLA and βLG has not been clarified. This study aimed to assess the efficacy of αLA and βLG in various animal models such as acetic acid-induced writhing, carrageenan-induced paw inflammation, and adjuvant induced-arthritis. Orally administered αLA 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, βLG had no effects in these animal models. To clarify the anti-nociceptive and anti-inflammatory mechanisms of αLA, we examined the levels of interleukin (IL)-6 and prostaglandin (PG)E2 in carrageenan-injected paw exudates. The administration of αLA 1 h before carrageenan injection inhibited the increased formation of IL-6 and PGE2 in paw exudates. Next, we demonstrated in vitro enzyme-inhibition assay; cyclooxygenase (COX), phospholipase A2, and 5-lipoxygenase. αLA inhibited COX and phospholipase A2 activities. αLA inhibited COX and phospholipase A2 activities. Moreover, αLA showed selectivity on COX-2 as compared with COX-1. However, 5-lipoxygenase activity was not affected by αLA. These results suggest that αLA is a safe and useful natural drug for patients that require anti-inflammatory drugs, as αLA is contained in dairy food and is frequently ingested as daily food. © 2009 Pharmaceutical Society of Japan.