Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2020; 26(43): 6795-6809
Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6795
Antifungal activity and antidiarrheal activity via antimotility mechanisms of (-)-fenchone in experimental models
Michelle Liz de Souza Pessoa, Leiliane Macena Oliveira Silva, Maria Elaine Cristina Araruna, Catarina Alves de Lima Serafim, Edvaldo Balbino Alves Júnior, Alessa Oliveira Silva, Matheus Marley Bezerra Pessoa, Hermes Diniz Neto, Edeltrudes de Oliveira Lima, Leônia Maria Batista
Michelle Liz de Souza Pessoa, Leiliane Macena Oliveira Silva, Maria Elaine Cristina Araruna, Catarina Alves de Lima Serafim, Edvaldo Balbino Alves Júnior, Alessa Oliveira Silva, Hermes Diniz Neto, Edeltrudes de Oliveira Lima, Department of Pharmaceutical Sciences, IPeFarM, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
Matheus Marley Bezerra Pessoa, Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil
Leônia Maria Batista, Postgraduate Program in Natural and Synthetic Bioactive Products, Universidade Federal da Paraiba, João Pessoa 58051-900, Brazil
Author contributions: Pessoa MLS, Silva LMO, Araruna MEC, Serafim CAL, Alves Júnior EB, Silva AO, Pessoa MMB, and Batista LM contributed to the conception and design of the study, performed the in vivo experiments, coordinated the study, participated in writing the manuscript and approved the final version to be published; Diniz Neto H and de Oliveira Lima E acted as contributors to the evaluation of antimicrobial activity.
Institutional review board statement: The study was reviewed and approved by the Commission for Ethics in Animal Experimentation (CEUA) of the Research Ethics Committee of the Federal University of Paraíba.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (approved by the Institutional Commission in Animal Use from Federal University of Paraíba (CEUA/UFPB) under No. 035/2017 and No. 4996090518/2018).
Conflict-of-interest statement: Authors declare that no conflict of interest exists.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Leônia Maria Batista, PharmD, Associate Professor, Professor, Postgraduate Program in Natural and Synthetic Bioactive Products, Universidade Federal da Paraiba, Cidade Universitária, s/n - Castelo Branco III, João Pessoa 58051-900, Brazil. leoniab@uol.com.br
Received: May 20, 2020
Peer-review started: May 20, 2020
First decision: July 29, 2020
Revised: August 12, 2020
Accepted: October 1, 2020
Article in press: October 1, 2020
Published online: November 21, 2020
Processing time: 178 Days and 8.6 Hours
ARTICLE HIGHLIGHTS
Research background

Pharmacological therapy for diarrhea is associated with contraindications and side effects. In the search for new therapeutic alternatives, natural products and medicinal plants are of great relevance, plant extracts, their semi-synthetic derivatives and synthetic compounds inspired by natural products make up the majority of drugs in use today. Many plant species and their isolated compounds, including terpenes, showed promising effects in the context of diarrhea, based on this criterion, the monoterpene (-)-fenchone was selected for this study.

Research motivation

(-)-Fenchone is a bicyclic monoterpene present in essential oils of plant species, such as Foeniculum vulgare and Peumus boldus, used in the treatment of gastrointestinal diseases. It has relevant pharmacological activities described in the literature. Many species of plants and their isolated compounds, including terpenes, have shown promising antidiarrheal and motility, based on this result, the monoterpene (-)-fenchone was selected for this study.

Research objectives

The main objective of our study was to evaluate the antidiarrheal activity related to gastrointestinal motility, intestinal secretion and antimicrobial and antifungal activity of (-)-fenchone.

Research methods

In this study, antidiarrheal activity was evaluated in vivo, using male Swiss mice. The effects of (-)-fenchone in the castor oil-induced diarrhea model. Intestinal transit and gastric emptying protocols were used to evaluate a possible antimotility impact. Muscarinic receptors, presynaptic α2-adrenergic and tissue adrenergic receptors, KATP channels, nitric oxide were investigated to uncover antimotility mechanisms of action and castor oil-induced enteropooling to elucidate antisecretory mechanisms. The antimicrobial activity was evaluated in the minimum inhibitory concentration model, the fractional inhibitory concentration index using the (-)-fenchone association method with standard antimicrobial agents.

Research results

(-)-Fenchone at doses (75, 150 and 300 mg/kg) has antidiarrheal activity, with a significant decrease in the evacuation index. This activity is possibly related to a percentage of reduced intestinal transit (75, 150 and 300 mg/kg). The antimotility effect of (-)-fenchone decreased in the presence of pilocarpine, yohimbine, propranolol, L-NG-nitroarginine methyl ester or glibenclamide. In the enteropooling model, no reduction in intestinal fluid weight was observed. (-)-Fenchone did not show antibacterial activity, inhibits the growth of strains of fungi with a minimum fungicidal concentration of 32 μg/mL. As for the association between (-)-fenchone and amphotericin B in strains of Candida albicans, it was observed that the association was indifferent.

Research conclusions

The antidiarrheal effect of (-)-fenchone found in this study involves antimotility and not involve antisecretory mechanisms. (-)-Fenchone has antifungal activity; however, it did not show antibacterial activity.

Research perspectives

The main limitations of our study include strains of tested bacteria that are not the most prevalent in infectious diarrhea, as well as other in vivo models of diarrhea and post-exposure treatment. The prospects are to perform other models of diarrhea in vivo that can help to reinforce these data, as well as other analyzes of molecular markers to characterize mechanisms.