Fatty acid amide hydrolase controls mouse intestinal motility in vivo.
Background & Aims: Fatty acid amide hydrolase (FAAH) catalyzes the hydrolysis both of the endocannabinoids (which are known to inhibit intestinal motility) and other bioactive amides (palmitoylethanolamide, oleamide, and oleoylethanolamide), which might affect intestinal motility. The physiologic role of FAAH in the gut is largely unexplored. In the present study, we evaluated the possible role of FAAH in regulating intestinal motility in mice in vivo. Methods: Motility was measured by evaluating the distribution of a fluorescent marker along the small intestine; FAAH messenger RNA (mRNA) levels were analyzed by reverse-transcription polymerase chain reaction (RT-PCR); endocannabinoid level…
Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon
Colorectal cancer is an increasingly important cause of death in Western countries. Endocannabinoids inhibit colorectal carcinoma cell proliferation in vitro. In this paper, we investigated the involvement of endocannabinoids on the formation of aberrant crypt foci (ACF, earliest preneoplastic lesions) in the colon mouse in vivo. ACF were induced by azoxymethane (AOM); fatty acid amide hydrolase (FAAH) and cannabinoid receptor messenger ribonucleic acid (mRNA) levels were analyzed by the quantitative reverse transcription polymerase chain reaction (RT-PCR); endocannabinoid levels were measured by liquid chromatography-mass spectrometry; caspase-3 and caspase-9 expressions were measured by W…
Inhibitory effect of caffeic acid phenethyl ester, a plant-derived polyphenolic compound, on rat intestinal contractility
Abstract Caffeic acid phenethyl ester (CAPE) exerts pharmacological actions (e.g. anti-inflammatory, chemopreventive) which are relevant for potential clinical application in the digestive tract. However, no study has been published on its possible effects on intestinal motility, to date. In the present study, we investigated the effect of this plant-derived polyphenolic compound on the spontaneous contractions of the rat isolated ileum. CAPE reduced (in a tetrodotoxin-insensitive manner) spontaneous ileal contractions and this effect was reduced by the l -type Ca 2+ channel blocker nifedipine and the chelant of calcium ethylenediaminetetraacetic acid. However, the effect of CAPE was not mo…
Antispasmodic Effects and Structure−Activity Relationships of Labdane Diterpenoids from Marrubium globosum ssp. libanoticum
Marrubium globosum ssp. libanoticum is a medicinal plant used in Lebanon to reduce pain and smooth muscle spasms. A chloroform extract obtained from M. globosum aerial parts reduced acetylcholine-induced contractions in the isolated mouse ileum. The purification of this extract identified, among 12 isolated labdane diterpenoids, four new compounds, named 13-epicyllenin A (4), 13,15-diepicyllenin A (5), marrulibacetal (9), and marrulactone (11). Their structures were determined by spectroscopic methods. Compound 9, which exerted antispasmodic activity, is likely the active ingredient of the extract. Preliminary structure-activity relationships for this class of compounds are suggested.
Best practice in research – Overcoming common challenges in phytopharmacological research
Abstract Background The pharmacology, toxicology and pharmacokinetics of bioactive preparations derived from natural sources has become a flourishing field of research. However, researching complex extracts and natural products faces numerous challenges. More broadly in recent years the critique of pharmacological research, and specifically its design, the methods used and reporting has intensified. Aims This consensus document provides a perspective on what constitutes best practice in pharmacological research on bioactive preparations derived from natural sources, providing a perspective of what the leading specialist journals in the field consider as the core characteristics of good rese…