Role of peripheral and central sensitization in the anti-hyperalgesic effect of hecogenin acetate, an acetylated sapogenin, complexed with β-cyclodextrin: Involvement of NFκB and p38 MAPK pathways

Neuropathic pain develops due to injury to the somatosensory system, affecting the patient's quality of life. In view of the ineffectiveness of the current pharmacotherapy, substances obtained from natural products (NPs) are a promising alternative. One NP that has been discussed in the literat...

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Published in:Neuropharmacology 2021-03, Vol.186, p.108395-108395, Article 108395
Main Authors: Santos Passos, Fabiolla Rocha, Pereira, Erik W.M., Heimfarth, Luana, Monteiro, Brenda S., Barbosa Gomes de Carvalho, Yasmim Maria, Siqueira-Lima, Pollyana S., Melo Coutinho, Henrique Douglas, Antunes de Souza Araújo, Adriano, Guedes da Silva Almeida, Jackson Roberto, Barreto, Rosana S.S., Picot, Laurent, Quintans-Júnior, Lucindo J., Quintans, Jullyana S.S.
Format: Article
Language:English
Subjects:
Biochemistry
Biochemistry, Molecular Biology
Inflammatory cytokines
Life Sciences
Medication
Microglia
Neuropathic pain
Pharmaceutical sciences
Sapogenin
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Summary:Neuropathic pain develops due to injury to the somatosensory system, affecting the patient's quality of life. In view of the ineffectiveness of the current pharmacotherapy, substances obtained from natural products (NPs) are a promising alternative. One NP that has been discussed in the literature is hecogenin acetate (HA), a steroidal sapogenin with anti-inflammatory and antinociceptive activity. However, HA has low water solubility, which affects its bioavailability. Thus, the objective of this study was to evaluate the anti-hyperalgesic activity of pure and complexed hecogenin acetate (HA/βCD) in an animal model of chronic neuropathic and inflammatory pain. The inclusion complex was prepared at a molar ratio of 1:2 (HA:βCD) by the lyophilization method. For the induction of chronic inflammatory pain, the mice received an intraplantar injection of CFA (complete Freund's adjuvant), and were evaluated for mechanical hyperalgesia and for the levels of myeloperoxidase (MPO) in the skin of the paw after eight days of treatment. HA and HA/βCD reduced mechanical hyperalgesia in relation to the vehicle group until the fourth and fifth hours, respectively, in the acute evaluation, with a superior effect of the complexed form over the pure form in the second and third hour after treatment (p 
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2020.108395