Analgesic activity of acetyl-11-keto-beta-boswellic acid, a 5-lipoxygenase-enzyme inhibitor

Acetyl-11-keto-beta-boswellic acid (AKBA) is one of the four major pentacyclic triterpenic acids present in the acidic extract of the Boswellia serrata gum resin that is used for a variety of inflammatory disorders, such as rheumatoid arthritis, osteoarthritis, and cervical spondylosis. AKBA is a novel, highly specific inhibitor of 5-lipoxygenase, the key enzyme for leukotriene biosynthesis. It inhibits 5-LOX either directly interacting with the enzyme itself, or interacting with 5lipoxygenase activating proteins (FLAP). Leukotriene, especially the LTB 4 , as well as the peptidoleukotrienes (LTC 4 LTD 4 , LTE 4 ) results in an increase in vascular permeability and chemotaxis of polymorphonuclear leukocytes, as well as release of mediators from the leukocytes, which sensitize nociceptors. 4] On the basis of the possible role of the leukotrienes in sensitization and provocation of nociceptors, the study was undertaken to assess the analgesic activity of AKBA (5-LOX inhibitor) in different pain models. Laca mice (20–30 g) of either sex, bred in the central animal house of Panjab University, Chandigarh, maintained at 12 h light/dark cycle was used for the study. Animals were housed under standard laboratory conditions, with free access to food and water. All the experiments were carried out between 0900 and 1700 h. All the experimental protocols were approved by the Institutional Animal Ethics Committee of the university. Standard (nimesulide [2 mg/kg]), and test (AKBA [50, 100 and 200 mg/kg]) drugs were prepared in 0.5% w/w carboxy-methylcellulose and administered p.o., half an hour before the onset of pain stimulus in the different models of nociception. Both the chemicals were obtained from M/s. Panacea Biotech, Ltd., Lalru, Punjab. Antinociceptive activity was assessed by two different models of nociception. Abdominal constrictions were induced by 1% v/v acetic acid solution (1 ml/kg, i.p.) in mice pretreated with saline solution or one of the test substances. The number of abdominal writhing was measured over 20 min after the injection of acetic acid, and the animals treated with nimesulide (2 mg/kg) were used as positive controls. Results were expressed as percent inhibition of abdominal constrictions. The central antinociceptive effect was determined using the tail flick test. The response was elicited every 30 min after the treatment with test sample. Five experimental groups were used. Results were expressed in % maximum possible effect (%MPE).