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

Biomed Pharmacother. 2017 Aug:92:324-330. doi: 10.1016/j.biopha.2017.05.073. Epub 2017 May 25.

Abstract

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 (10-177μg) and mexicanolide 1 (0.5-3.5μg) exhibited concentration-dependent antihyperalgesic action in NA-STZ hyperglycemic mice. Ketanserin (6μg), a 5-HT2A/C receptor antagonist, and flumazenil (6μg), a GABAA receptor antagonist, abolished the antihyperalgesic effect of mexicanolide 1 (3μg). On the other hand, naloxone (3μg), L-arginine (50μg), and Nω-Nitro-l-arginine methyl ester hydrochloride (150μg) diminished the antihyperalgesic effect of mexicanolide 1. The aqueous extract of the seeds possesses significant antihyperalgesic action. Compound 1 produces antihyperalgesia through GABAA, 5-HT2A/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.

Keywords: 2-Hydroxy-destigloyl-6-deoxyswietenine acetate; Antihyperalgesia; Diabetes; Formalin; Hyperalgesia; Swietenia humilis.

MeSH terms

  • Analgesics / isolation & purification
  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Limonins / isolation & purification
  • Limonins / pharmacology
  • Limonins / therapeutic use*
  • Male
  • Meliaceae*
  • Mice
  • Mice, Inbred ICR
  • Niacinamide / toxicity
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Seeds
  • Streptozocin / toxicity

Substances

  • Analgesics
  • Hypoglycemic Agents
  • Limonins
  • Plant Extracts
  • mexicanolide
  • Niacinamide
  • Streptozocin