Nonsteroidal antiinflammatory drugs include the traditional drugs and more selective
COX-2 inhibitors. Traditional nonsteroidal antiinflammatory
drug use is hampered by their gastrotoxicity, while COX-2-inhibitors increase the cardiovascular risk. The search of safer substances for managing inflammatory conditions is updated, a challenge wherein dual COX/5-LOX inhibitors have a place. This review summarizes the benefits of
D-002, a mixture of higher aliphatic
beeswax alcohols, on joint health and gastric mucosa.
D-002 elicits gastroprotection through a multiple mechanism that involves the increased secretion and improved quality of the gastric mucus, the reduction of
hydroxyl radical, lipid peroxidation,
protein oxidation, neutrophil infiltration and the increase of
antioxidant enzymes on the gastric mucosa. Consistently,
D-002 inhibits
NSAIDs,
ethanol, pylorus-
ligation and
acetic acid-induced gastric ulceration in rats, and has reduced gastrointestinal symptoms in clinical studies. Early results found that
D-002 was effective in the cotton pellet-induced
granuloma and
carrageenan-induced
pleurisy model in rats, lowering pleural
leukotriene B4 levels without causing gastrointestinal ulceration. However,
D-002 effects on
inflammation received little attention for years. Recent data have shown that
D-002 inhibited both COX and 5-LOX activities with a greater affinity for 5-LOX and could act as a dual COX/5-LOX inhibitor. This mechanism might explain efficacy in experimental inflammatory and osteoarthritic models as well as clinical efficacy in osteoarthritic patients while supporting the lack of
D-002 gastrotoxicity, but not the gastroprotective effects, which appear to be due to multiple mechanisms. In summary oral
D-002 intake could help manage inflammatory conditions that impair joint health, while offering gastroprotection.