O óleo essencial de Mesosphaerum suaveolens (L.) Kuntze (Lamiaceae) promove efeito tocolítico in vitro em rata por modulação de receptores muscarínicos, de canais de cálcio e de potássio

Abstract

The specie from Mesosphaerum genus of Lamiaceae family, Mesosphaerum suaveolens, is popularly used for digestive disorders and to relief menstrual cramps. From the leaves of this species, the essencial oil (MS-EO) was extracted and, thus, we aimed to perform a pharmacological screening and to investigate the mechanism of action of the essencial oil from Mesosphaerum suaveolens in virgin rats. Then, uterine horns were suspended in orghan baths, under appropriate conditions, and isotonic and isometric contractions were monitored. All experimental procedures were approved by Ethical Comitee on Animal Use (CEUA)/UFPB (nº 088/2016). MS-EO antagonized, in a concentration dependente manner, phasic contractions induced by carbachol (CCh) 10-5 M (IC50 = 19.0 ± 1.3 μg/mL, n = 5), presenting Emax value of 100% in the concentration of 81 μg/mL, and by oxytocin 10-2 IU/mL (IC50 = 33.8 ± 4.7 μg/mL, n = 5), showing Emax value of 100% in the concentration of 243 μg/mL. Besides that, we decided to investigate the mechanism of tocolytic action of MS-EO, and it inhibited the cumulative concentration-response curves to CCh, rightward sifting them in a non parallel manner, with reduction on Emax, sugesting a pseudo-irreversible non-competitive antagonism of muscarinic receptors, in addition to relaxing, in an equipotente manner, the utherus pre-contracted by either KCl 60 mM or oxytocin 10-2 IU/mL (EC50 = 15.0 ± 2.6 and 20.2 ± 0.8 μg/mL, respectively). As the common step in the pathway of both contractile agents is the opening of voltage-sensitive Ca2+ channels (CaV), we decided to assess the probably inhibbitory effect of SM-EO on Ca2+ influx. MS-EO antagonized the cumulative concentration-response curves to CaCl2, in depolarizing médium nominally Ca2+-free, besides relaxed the utherus pre-contracted by the CaV-1 agonist S-(-)-Bay K8644 3 x 10-7 M, indicating a possible attenuation of Ca2+ influx through CaV1. Since that K+ channels have an essential role in regulating the potential membrane and that they modulate CaV, we decided to investigate the involvement of these channels in the tocolytic efect of MS-EO. The potency of MS-EO (EC50 = 20.2 ± 0.8 μg/mL) was about 1.5-fold reduced in the presence of CsCl (EC50 = 32.2 ± 2.0 μg/mL), an inespecific blocker of K+ channels, confirming the participation of these channels in the tocolytic effect of MS-EO. Therefore, in this work we support the popular use of Meshosphareum suaveolens for uterine disorders and we concluded that the tocolytic effect of MS-EO in rat occurs, at least in part by pseudo-irreversible non competitive antagonism type of muscarinic receptors, in addition to the blockade of CaV1 and positive modulation/activation of K+ channels. However, there is the need of additional studies to better understand how the essential oil modulates these channels and confirm the subtypes of K+ channels related to this effect.