Abstract:
Introduction: Grewia similis belongs to the family Tiliaceae, its stem bark and leaves are
traditionally used by traditional healers in Tanga Region for various conditions including;
induction of labour in pregnant women and as an abortifacient.
Aim of the study: The purpose of this study was to evaluate uterotonic activity, phytochemical
classes and compound(s), and possible mechanisms by which extracts of G. similis stem bark and
leaves stimulate uterine contraction.
Methodology: The study was experimental design conducted from April to July 2021. The plant
materials were collected from Tanga Region in August 2020 and the plant authentication was done
at University of Dar es Salaam (UDSM). Extracts were prepared by exhaustive cold maceration
using 95% ethanol, dried in a rotary evaporator and then fractionated by Vacuum Liquid
Chromatography (VLC) using dichloromethane (DCM), ethyl acetate (EtOAc), and ethanol
(EtOH).
Ex vivo uterotonic activity was carried out using healthy female young adult rats weighing between
120 and 200 g. To deduce the possible mechanism(s) of action, different concentrations of plant
extracts were administered alone and in the presence of the relevant uterine receptor antagonists.
Phytochemical analysis was done by using standard qualitative procedures of colour reactions.
Results of all quantitative data were expressed as mean ± SD (n=3), EC50 and Emax were
determined, analyzed by one-way ANOVA followed by post hoc Dunnett’s Multiple Comparison
test, p <0.05 was considered as a significant level. For phytochemical evaluation, qualitative results
were reported as positive or negative.
Results: The extraction yields were 2.5 and 1.6% for barks and leaves, respectively, while the
fraction yields were 48.5, 39.3 and 7.9% for DCM, EtOAc and EtOH, respectively. Crude
ethanolic bark and leaf extracts of G. similis and fractions from the stem bark were shown to cause
rat uterine muscle contraction. The crude stem bark ethanolic extract (GSBE) exhibited high
uterotonic activity as compared to crude leaf ethanolic extract (GSLE), significant differences (p
< 0.05) were observed in the EC50 and Emax. EtOH fraction from the stem bark of G. similis (GSBE 3) had shown high efficacy in uterotonic activity, statistically significant difference in the EC50
and Emax, when compared to GSBE, stem bark EtOAc fraction (GSBE-2) and stem bark DCM
fraction (GSBE-1) (p < 0.05). In deduction of the possible mechanism of action through uterine
contraction inhibition, significant differences (p < 0.05) were observed in the EC50 and Emax of
xiv
GSBE-3 alone and in the presence of some of uterine receptor antagonists. Pre-treating the isolated
uterine tissue with either calcium channel blocker-nifedipine, prostaglandins receptor antagonist meloxicam or histamine receptor antagonist-diphenhydramine before administering the extract
showed an inhibitory effect on uterine contraction while in the presence of muscarinic receptor
antagonist-atropine no effect was observed. The phytochemical screening revealed the presence of
tannins, flavonoids, steroids and saponins.
Conclusion: This study had revealed the uterotonic activity of crude ethanolic extracts and
fractions of G. similis stem barks. Both polar and non-polar fractions of the stem bark extracts
exhibited uterotonic properties (most polar fraction i.e, GSBE-3, being the most active). The
pharmacological effects/possible mechanisms results suggest that the stimulation of uterine
contractility by the stem bark ethanolic fraction of G. similis may arise from the interference with
calcium channels, stimulation of prostaglandin synthesis and/or activation of histamine H1-
receptors in utero. Uterotonic activity obtained could be due to the phytochemicals detected in G.
similis.
Further work is needed to isolate and identify the active metabolites and their mechanisms of
uterotonic action, toxicological studies, and standardization/formulation of G. similis bark and leaf
products.