Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. – An in vitro and in vivo study

• Published in: Phytomedicine (Stuttgart) 2018-09, Vol.48, p.32-42
• Main Authors: Monji, Faezeh, Adaikan, P Ganesan, Lau, Lang Chu, Siddiquee, Abrar Al-Mahmood, Said, Baharudin Bin, Yang, Lay-Kien, K., Yoganathan, Choolani, Mahesh A
• Format: Article
• Language: English
• Subjects: Ananas comosus; Intrauterine pressure; MMP-13; Serotonin; Uterine contraction
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2018.05.004

Ananas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries. Our previous in vitro experiments showed that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human uterine contractions. The aim of this study was to identify the bioactive compound and further investigate the molecular mechanism of F4 induced contraction and the in vivo uterotonic effect of F4. Organ bath studies were employed to compare the stimulatory effect of F4 in non and late pregnant uterine tissue followed by isolation of protein from late pregnant uterine tissue for the western blot analysis. The PhysioTel transmitter was implanted in pregnant SD rats to measure the changes in intrauterine pressure (IUP). Analyses of the crude extract and active principle in F4 was performed using LC-HRMS. Ripe F4 in a similar manner as serotonin produced a greater stimulatory response in late pregnant than non-pregnant uterine tissue without significant change in potency; ripe F4 also increased ERK phosphorylation which eventually led to a significant increase of the final product, MMP-13. In pregnant rats (E18), oral ripe F4 (1.5 g.100 g−1 body weight) and ergometrine (1 mg) did not stimulate the uterine contraction probably due to the low level of estradiol and as a consequence low 5-HT receptors at the time of administration. In contrast, in postpartum rats, oral administration of F4 and ergometrine produced a significant increase in maximal IUP to 4.3 and 4.9 folds of basal IUP respectively. Contrary to the folklore use, unripe F4 did not stimulate the uterine activity during pregnancy and postpartum. Bioassay guided fractionation identified serotonin as a major bioactive compound in ripe F4. Our data clearly indicate that the uterotonic effect of ripe F4 is mediated via the serotonergic pathway and suggest that serotonin rich diet may increase the peripheral serotonin and implicate in diverse physiological functions, including uterine motility. [Display omitted]