Host–guest inclusion complexation of β-cyclodextrin and hecogenin acetate to enhance anti-hyperalgesic effect in an animal model of musculoskeletal pain. (August 2017)

• Record Type: Journal Article
• Authors: Quintans, Jullyana S.S.; Pereira, Erik W.M.; Carvalho, Yasmim M.B.G.; Menezes, Paula P.; Serafini, Mairim R.; Batista, Marcus V.A.; Moreira, Carlos D.L.F.A.; Lima, Ádley A.N.; Branco, Alexsandro; Almeida, Jackson R.G.S.; Gelain, Daniel Pens; Zengin, Gokhan; Araújo, Adriano A.S.; Quintans-Júnior, Lucindo J.
• Is Part Of: Process biochemistry. Volume 59:Part A(2017)
• Page Start: 123
• Page End: 131
• Publication Date: 2017-08
• Subjects: FM fibromyalgia -- NP natural product -- HA hecogenin acetate -- CD cyclodextrin -- PM physical mixture -- SC slurry complexation -- SP substance P; Hecogenin -- Cyclodextrin -- Opioid -- Substance P -- Pain -- Fibromyalgia; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2016.08.025
• Languages: English
• ISSNs: 1359-5113

Abstract

Graphical abstract: Highlights: The HA/β-CD inclusion complex was prepared and characterized. β-CD enhance the anti-hyperalgesic effect of HA. Anti-hyperalgesic effect of HA/β-CD seems to be mediated by the opioid system. Abstract: Hecogenin acetate (HA), a steroidal acetylated-sapogenin, has an analgesic profile already assigned, but its low water solubility and short half-life limit its use in chronic conditions. β-cyclodextrin (β-CD) can improve the chemical and pharmacological property of nonpolar compounds such as HA. Therefore, a HA complexed with β-CD (HA-CD) was prepared and characterized by thermal, morphological and spectroscopic analysis. A model of chronic musculoskeletal pain was induced by means of two injections of pH 4.0 saline (20 μL) into the left gastrocnemius 5 days apart was used. After confirming hyperalgesia, male mice were treated with HA, HA-CD (20 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.). Motor coordination tests, substance P (SP) levels in a lumbosacral (L4-S2) spinal cord sample and a docking study were equally assessed to check for a possible action on the opioid receptors. Oral pretreatment with HA or HA-CD produced a significant antinociceptive (p < 0.01) profile and also decreased mechanical hyperalgesia, with HA-β-CD showing significantly better effects when compared to HA alone (p < 0.05). The interaction between HA and the opioid receptor (MU, Kappa, Delta) was corroborated by the docking study. Moreover, the SP level was reduced in a spinal cord sample. Our findings suggest that β-CD can improve the anti-hyperalgesic effect of HA in an animal model of musculoskeletal pain.