Extraction of spilanthol in the context of green chemistry and its application in the treatment of oral mucositis

Author(s)

Veronica Santana de Freitas Blanco

• Document type: Doctoral Thesis
• Press: Piracicaba, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2018-02-19

Examining board members

Rodney Alexandre Ferreira Rodrigues; Severino Matias de Alencar; Fernanda Oliveira de Gaspari de Gaspi; Maria Cristina Volpato; Michelle Franz Montan

• Advisor: Rodney Alexandre Ferreira Rodrigues

Abstract

The extraction of bioactive compounds from plants is usually associated with the use of toxic organic solvents, which, as a consequence, generate waste with high environmental impact and high operating costs. For this reason, the use of processes that eliminate or minimize the use of organic solvents, such as supercritical fluid extraction using CO2, is of great interest. Spilanthol, an alkylamide found in various species, among them, Acmella oleracea (L.) R.K. Jansen has several pharmacological properties, such as anti-inflammatory, anesthetic, and antioxidant activity. These properties may be of great interest for the treatment of oral mucositis, one of the most common side effects from the treatment of cancer patients undergoing radiotherapy and chemotherapy. Therefore, the purpose of this work was to isolate the spilanthol contained in the aerial parts of Acmella oleracea employing green chemistry techniques and evaluate its anti-inflammatory activity through in vitro and in vivo models, as well as, the incorporation of spilanthol in an oral formulation aimed to treat of oral mucositis. It was possible to obtain high purity (97%) spilanthol employing green extraction techniques, such as extraction followed by fractionation using supercritical carbon dioxide, with subsequent isolation of the spilanthol by Flash chromatography, using as solvents, ethanol, and water. In the in vitro evaluation, it was possible to determine the low toxicity of spilanthol to human gingival fibroblasts (HGF-1) in concentrations of up to 200 ?M, and also its suppressor effect in the expression of genes involved in the inflammatory process, such as Selectin E and Interleukin-9. In the in vivo experiment, spilanthol, at 30 mg/kg, was able to significantly attenuate the inflammation caused by 5-FU chemotherapy in a model of intestinal mucositis in Swiss mice. It was also possible to develop a promising formulation containing spilanthol for a possible use in mucositis (AU)

• FAPESP's process: 14/06461-2 - Extraction of espilantol in the context of green chemistry and its application in the treatment of oral mucositis
• Grantee: Verônica Santana de Freitas Blanco
• Support Opportunities: Scholarships in Brazil - Doctorate