Pheophorbide-a, a chlorophyll derivative, inhibits myometrial contractility ex vivo via blockade of extracellular and intracellular Ca2+−entry

Adaeze P. Uchendu, Eric K. I. Omogbai, Philip Obarisiagbon, Uyi G. Omogiade, Enitome E. Bafor
In: Scientific African · 2024 · vol. 25 , pp. e02286 · doi:10.1016/j.sciaf.2024.e02286 · W4399708889
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Abstract

Preterm delivery is associated with neonatal complications such as neurological impairment and necrotising enterocolitis. Thus, suppression of early myometrial contractility in pre-term labor (PTL) delays delivery and reduces maternal adverse outcomes associated with PTL. However, most tocolytics exert varied efficacies and untoward outcomes such as maternal cardiovascular and respiratory effects creating a need for novel efficacious and safe tocolytics. We previously reported that chlorophyll derivatives including Pheophorbide-a (PBa) isolated from the leaves of the plant Ficus exasperata, effectively inhibited non-pregnant mouse myometrial contractility ex vivo. Therefore, the current study explores the mechanisms involved in PBa-induced myometrial contractility inhibition in both non-pregnant and pregnant mouse uterus. We carried out contractility studies by inducing isometric tension on isolated myometrial strips of mice following ex vivo exposure to PBa. The uterine strips were mounted in organ baths containing oxygenated physiological saline maintained at pH 7.4 and 36.8 ± 0.2 °C. PBa (0.02–206.19 µM) produced concentration-dependent decreases in the amplitude and frequency of pregnant and non-pregnant uterine contractions. In addition, PBa (87.74 μM) significantly inhibited the amplitude (P = 0.0026) and frequency (P = 0.0178) of OT-induced uterine contractility in Ca2+−free solution and in the presence of high KCl (80 mM) (P = 0.005). Furthermore, our study showed that the uterine relaxant effect of PBa occurred through the blockade of l-type voltage-gated Ca2+channels (VGCCs) and through inhibition of Ca2+ mobilization from intracellular stores which are common downstream pathways specific to tocolytics and relevant for uterine relaxation. These findings reveal that PBa effectively attenuates uterine contractions via interaction with Ca2+−entry and shows potential as a promising candidate as a tocolytic therapy for PTL. Further investigations on PBa are encouraged to elucidate molecular and cellular mechanisms of PBa uterine relaxation activity including assessment of efficacy and off-target effects.

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