Inhibition of Neuromuscular Contractions of Human and Rat Colon by Bergamot Essential Oil and Linalool: Evidence to Support a Therapeutic Action

Abstract

Bergamot essential oil (BEO) added to food and drink promotes a citrus flavour. Folklore suggests benefits on gastrointestinal functions but with little supporting evidence. BEO and major constituents (linalool, limonene, linalyl acetate) were therefore examined for any ability to influence neuromuscular contractions of human and rat colon. Circular muscle strips (macroscopically-normal human colon obtained following ethical approval at cancer surgery; Sprague–Dawley rats) were suspended in baths (Krebs solution; 37 °C; 5% CO2 in O2) for measurement of neuronally-mediated contractions (prevented by tetrodotoxin or atropine) evoked by electrical field stimulation (5 Hz, 0.5 ms pulse width, 10s/minute, maximally-effective voltage), or contractions evoked by KCl (submaximally-effective concentrations). BEO and each constituent concentration dependently inhibited neuronally-mediated and KCl-induced contractions. In human: apparent pIC50 for BEO (volume/volume Krebs), respectively, 3.8 ± 0.3 and 4.4 ± 0.3; Imax 55.8% ± 4.2% and 37.5% ± 4.2%. For the constituents, the rank order of potency differed in human (linalool > limonene >> linalyl-acetate) and rat colon (linalyl-acetate > limonene = linalool), but rank order of efficacy was similar (linalool >> (BEO) = linalyl-acetate >> limonene). Thus, linalool had high efficacy but greater potency in human colon (Imax 76.8% ± 6.9%; pIC50 6.7 ± 0.2; n = 4) compared with rat colon (Imax 75.3% ± 1.9%; pIC50 5.8 ± 0.1; n = 4). The ability of BEO and linalool to inhibit human colon neuromuscular contractility provides a mechanism for use as complementary treatments of intestinal disorders.

Contractility of isolated colonic smooth muscle strips from rats treated with cancer chemotherapy: differential effects of cisplatin and vincristine

“…The phasic component exhibited a greater response in both muscles (LM and CM) across all cases (controls, cisplatin, and vincristine) and regardless of the timing of KCl administration (initial or final). The lower amplitude of the tonic component compared to the phasic component aligns with previous studies ( Sánchez et al, 2017 ; Straface et al, 2020 ).…”

“…In the in vitro study of colonic contractility, we evaluated two different types of muscular response: the neuronal response to EFS (which activates the release of different neurotransmitters from the myenteric neurons, Thein et al, 2020 ) and the muscular response to ACh (which activates cholinergic receptors, particularly the muscarinic receptors present in the muscle cells). KCl was used to evoke non-specific muscle and nerve activation ( Yildiz et al, 2007 ; Straface et al, 2020 ).…”

“…The KCl response was utilized as a reference for tissue integrity and a maximal response, as reported previously ( Yildiz et al, 2007 ; Straface et al, 2020 ). An exclusion criterion was established to ensure that only viable preparations were included, avoiding the use of preparations possibly damaged during manipulation.…”

“…Our findings are in general agreement with previous results obtained in humans ( Aulí et al, 2008 ; Broad et al, 2012 , 2019 ) and rats ( Zaw et al, 2016 ). Interestingly, the A1 component of intestinal EFS-induced contractile responses is considered to be mainly due to the release of ACh from myenteric neurons and activation of muscarinic receptors ( Kondo et al, 2011 ; Straface et al, 2020 ; Tanahashi et al, 2021 ), although purinergic [at low frequencies ( Aulí et al, 2008 )] and nitrergic ( Van Crombruggen and Lefebvre, 2004 ) activation may also occur ( Burnstock, 2014 ). In contrast, the contractile response occurring after electrical stimulation (A2) is a result of the release of both ACh and substance P from myenteric neurons ( Aulí et al, 2008 ), and its inhibition requires the combined action of atropine and neurokinin receptor antagonists ( Aulí et al, 2008 ; Broad et al, 2012 ; Mañé et al, 2014 ), although other mechanisms, such as purinergic and nitrergic involvement, cannot be ruled out ( Van Crombruggen and Lefebvre, 2004 ).…”

Bergamot rehabilitation AgaINst agitation in dementia (BRAINAID): Study protocol for a randomized, double‐blind, placebo‐controlled trial to assess the efficacy of furocoumarin‐free bergamot loaded in a nanotechnology‐based delivery system of the essential oil in the treatment of agitation in elderly affected by severe dementia

“…Patients will be randomly allocated to BEO cream group or placebo group in a 1:1 allocation ratio. Since there are not differences induced by the gender of the participants (McDonnell & Newcomb, 2019 ; Straface et al, 2020 ; Xiong et al, 2018 ) or other parameters, no factors for stratification will be considered. No blocking, for example, incomplete randomization, will occur.…”