Antihyperalgesic activity of a mexicanolide isolated from Swietenia humilis extract in nicotinamide-streptozotocin hyperglycemic mice

Swietenia humilis Zucc. (Meliaceae) seeds are used in Mexico for the treatment of type 2 diabetes mellitus. Mexicanolides are the main hypoglycemic and antihyperglycemic compounds of the species. This study was conducted to investigate the antihyperalgesic effect of an aqueous extract of the seeds of Swietenia humilis (SHAE) and of mexicanolide 2-hydroxy-destigloyl-6-deoxyswietenine acetate (1), using the formalin test in mice. The antihyperalgesic actions of SHAE and mexicanolide 1, as well as its possible transductional activity, were assessed in nicotinamide-streptozotocin (NA-STZ) hyperglycemic mice. Local injection of SHAE (10–177 μg) and mexicanolide 1 (0.5–3.5 μg) exhibited concentration-dependent antihyperalgesic action in NA-STZ hyperglycemic mice. Ketanserin (6 μg), a 5-HT_2A/C receptor antagonist, and flumazenil (6 μg), a GABA_A receptor antagonist, abolished the antihyperalgesic effect of mexicanolide 1 (3 μg). On the other hand, naloxone (3 μg), L-arginine (50 μg), and Nω-Nitro-L-arginine methyl ester hydrochloride (150 μg) diminished the antihyperalgesic effect of mexicanolide 1. The aqueous extract of the seeds possesses significant antihyperalgesic action. Compound 1 produces antihyperalgesia through GABA_A, 5-HT_2A/C and opioid receptors. Also, the nitrergic system is involve in the antihyperalgesic effect of 1. Data obtained with Swietenia humilis Zucc. seeds give evidence of its potential for pain associated with diabetes treatment.