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

Abstract

In recent years, milk constituents have become recognized as functional foods, suggesting that their use has a direct and measurable effect on health outcomes. Milk contains two primary sources of protein, the caseins and whey. After processing, the caseins are the proteins responsible for making curds, while whey remains in an aqueous environment. Whey has been touted as a functional food with a number of health benefits.1) The protein fraction in whey comprises four major protein fractions and six minor protein fractions. The major protein fractions in whey are a-lactalbumin (aLA), b-lactoglobulin (bLG), bovine serum albumin, and immunoglobulins. The biological components of whey demonstrate a range of immune-enhancing properties.2) In addition, whey has the ability to act as an antioxidant, 3) antihypertensive, 4) antitumor, 5) hypolipidemic, 1) antiviral, 6) antibacterial, 7) and chelating agent. 8)It is well-known that lactoferrin, the minor component of whey proteins, inhibits production of the inflammatory cytokines tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 in monocytes. We have confirmed that lactoferrin protects TNF-a production caused by sensitization of hepatic monocytes (kupffer cells) by lipopolisaccaride.9) It has recently been reported that lactoferrin produces analgesia in the thermal, visceral and formalin-evoked nociceptions in rats.10) However, the efficacy of other proteins has not been clarified with regard to analgesic action.Prostaglandins (PGs) formed by the phospholipase A 2 (PLA 2 ) and cyclooxygenase (COX) enzymes are important mediators of nociception and inflammation.11) On the other hand, emerging information has pointed to the role of another arachidonic acid metabolic pathway (the 5-lipoxygenase (5-LO) pathway) in producing and maintaining inflammation.12) There is evidence that COX-2 and 5-LO are co-expressed and up-regulated in a number of inflammatory diseases and that COX-2 as well as 5-LO inhibitors have beneficial effects in inflammatory diseases. 13)The aim of the present study was to assess three points: 1) Can orally administered aLA potentiate an anti-nociceptive response? 2) Can orally administered aLA potentiate an antiinflammatory response? 3) If so, are COX, PLA 2 , and 5-LO involved in this potentiation by aLA? In this study, we used acetic acid-induced mouse writhing and for pain, carrageenaninduced rat paw edema for acute inflammation, and adjuvantinduced rat arthritis for chronic inflammation. MATERIALS AND METHODS AnimalsMale ICR mouse weighing from 20 to 25 g and male Wistar rats weighing from 150 to 200 g were obtained from SLC Japan, Inc. (Shizuoka, Japan) and housed in plastic cages for 1 week prior to the commencement of experiments under controlled temperature (21Ϯ2°C), humidity (55Ϯ15%), and 12-h light/dark cycle, and the light period was from 7:00 to 19:00. Commercially available rat chow and water were provided ad libitum. This study was performed in accordance with "The guidelines of the Meiji Dairies Corporation for the care and use...

Novel Dipeptidyl Peptidase-4–Inhibiting Peptide Derived From β-Lactoglobulin

“…We also reported anti-inflammatory and analgesic activity of α-lactoalbumin (10). Milk products are powerful acute stimulants of insulin secretion (11,12) and have the ability to enhance the insulin response when supplied in a mixed meal (13).…”

Chronic Administration of Bovine Milk-Derived α-Lactalbumin Improves Glucose Tolerance <i>via</i> Enhancement of Adiponectin in Goto–Kakizaki Rats with Type 2 Diabetes

“…We already reported that oral administered bovine milk-derived α-lactalbumin had anti-inflammatory activity inhibiting by COX-2. 16) Recently, it has been reported that dairy protein affect expression of PPARγ mRNA 24,25) From these results, α-lactalbumin suppressed adipose tissue inflammation and the ameliorating effects of α-lactalbumin on glucose intolerance in GK rats might be mostly caused by enhancement of adiponectin. In addition, α-lactalbumin might improve insulin sensitivity via enhancement of adiponection in peripheral tissues, but we have no data about glucose uptake in peripheral tissued or hepatic glycogenesis induced by insulin.…”

“…13) We have confirmed that lactoferrin protects tumor necrosis factor-α (TNF-α) production caused by sensitization of hepatic monocytes (kupffer cells) by lipopolisaccaride in C57BL/6J mice. 14) We also reported that oral administered bovine milk-derived α-lactalbumin (300 mg/kg) had anti-inflammatory 15) and anti-nociceptive activity by inhibiting cyclooxygenase-2 (COX-2) 16) in rat. The aim of the present study was to assess two points: 1) Can dietary treatment with α-lactalbumin improve impaired glucose tolerance?…”

A Proteomic Study on Donkey Milk

“…This complex may be considered as a potential therapeutic agent against various tumor cells [43,44]. Other authors [45] have demonstrated the anti-inflammatory activity of α-lactalbumin through the inhibition of cyclooxygenase-2 (COX-2) and phospholipase A 2 activities. Figure 4c shows the electropherogram for the donkey milk highmolecular-weight whey proteins separated by 2-DE (first dimension: IPG-strip pH 3-11, second dimension: 7.5% SDS-PAGE).…”