Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6795
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
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.
(-)-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.
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.
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.
(-)-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.
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.
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.