# Essential oil from Xylopia frutescens Aubl. reduces cytosolic calcium levels on guinea pig ileum: mechanism underlying its spasmolytic potential

## TL;DR

This study shows that the essential oil from Xylopia frutescens reduces calcium levels in gut muscle cells, helping to relax the muscle and support its use as an antidiarrheal.

## Contribution

The study identifies a novel mechanism of spasmolytic action involving calcium influx blockade and histaminergic receptor antagonism.

## Key findings

- XF-EO inhibits histamine- and CCh-induced contractions in guinea pig ileum.
- XF-EO reduces intracellular calcium levels in intestinal myocytes.
- The essential oil blocks calcium influx through Cav1 channels.

## Abstract

Xylopia frutescens Aubl. (embira, semente-de-embira or embira-vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum.

The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4.

Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre-contracted with KCl, it was hypothesized that XF-OE would be acting as a K+ channel positive modulator. In the presence of CsCl (non-selective K+ channel blocker), the relaxant potency of XF-OE was not altered, indicating a non-participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca2+ and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration-dependent manner, thus, was confirmed the inhibition of Ca2+ influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in the presence of XF-OE and the Fluo-4-associated fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca2+]c reduction.

Spasmolytic action mechanism of XF-EO on guinea pig ileum can involve histaminergic receptor antagonism and Ca2+ influx blockade, which results in [Ca2+]c reduction leading to smooth muscle relaxation.