Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection

• Published in: Life sciences (1973) 2021-01, Vol.265, p.118742, Article 118742
• Main Authors: de Souza, Eloísa Portugal Barros Silva Soares, Gomes, Marcelo Vinicius Lins Dantas, dos Santos Lima, Bruno, Silva, Luiz André Santos, Shanmugan, Saravanan, Cavalcanti, Marcelo Duarte, de Albuquerque Júnior, Ricardo Luiz Cavalcanti, de Souza Carvalho, Flavio Machado, Marreto, Ricardo Neves, de Lima, Claudio Moreira, Júnior, Lucindo José Quintans, de Souza Araújo, Adriano Antunes
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Anti-Ulcer Agents - pharmacology; Arthritis; Arthritis - drug therapy; Arthritis, Experimental - drug therapy; beta-Cyclodextrins - pharmacology; Cartilage; Cell Line; Cyclodextrins; Cytotoxicity; Ethanol; Freeze drying; Gastric Mucosa - metabolism; Gastric ulcer; Inclusion complexes; Indomethacin; Indomethacin - pharmacology; Inflammation; Inflammatory diseases; Joint diseases; Joints; Leukocyte migration; Leukocytes (neutrophilic); Male; Medical treatment; Mice; Nerolidol; Neutrophils; NMR; Nonsteroidal anti-inflammatory drugs; Nuclear magnetic resonance; Plant Extracts - pharmacology; Rheumatoid arthritis; Sesquiterpenes - pharmacology; Stomach - pathology; Stomach Ulcer - chemically induced; Terpene; Toxicity; Ulcers; Zymosan; β-Cyclodextrin
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118742

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug. [Display omitted]