ABSTRACT
The use of traditional remedies for conditions affecting reproduction is becoming popular and widely accepted, and a lot of plants used in these remedies are yet to be scientifically investigated. Moringa oleifera leaf (MOL) has been reported to have effect on uterine activities, but there is paucity of information on the exact constituent responsible for this effect. Hence, phytochemicals extracted and fractionated from MOL were tested on the uterus, in vivo, in vitro and in silico. In the in vivo study, fifty-three (53) adult wistar rats (18 males and 35 females) were used. Female rats were mated with male rat (2:1). Pregnant animals were randomly divided into 7 groups. From Day 7 to Day 14 of pregnancy, Group 1 was treated with 0.5ml of distilled water. Groups 2, 3 and 4 were treated with 60 mg/kg of alkaloid, glycoside and peptide fractions of MOL respectively. Groups 5, 6 and 7 were treated with 120 mg/kg of alkaloid, glycoside and peptide fractions respectively. On Day 15 of pregnancy, animals were sacrificed. For the main in vitro study, 10 female wistar rats were used, n =5 for effect on spontaneous contractions and n =5 for the mechanism of action. Only Alkaliod fraction of MOL (AMOL) showed significant effect on spontaneous contraction, AMOL was further fractionated into chloroform, n-hexane and dichloromethane fractions. Chloroform fraction (CAMOL) was the most active and its effect and mechanism of action was tested on an isolated uterus of female wistar rats. Compounds present in CAMOL were investigated via GC-MS. In the in silico study, compounds present in CAMOL were docked with OXTR, ERs, COX-1 and TNF-α and their pharmacokinetic properties were investigated. In vivo result showed that pregnancy was maintained in all groups, significant increase in progesterone, FSH, cytokines, total protein, GSH and MDA levels in some treatment groups and a significant decrease in SOD, MDA and CAT levels in some treatment groups compared to Group 1. In vitro study; AMOL and CAMOL significantly inhibited spontaneous contractions. CAMOL significantly inhibited oxytocin-induced, KCl-induced and calcium-free solution contractions. In silico study; 6 out of 47 compounds present in CAMOL had a significant higher binding affinity for OXTR, ERs, COX-1 and TNF-α and the pharmacokinetic investigation showed that these 6 compounds were likely oral drug candidates. In conclusion, phytochemicals extracted from MOL has significant effect on uterine activities. In vivo; pregnancy was maintained and changes in hormonal and other biochemical parameters in the uterine tissue were observed. In vitro; AMOL and its active fraction CAMOL inhibited contractions. In silico; compounds present in CAMOL bind with proteins to prevent contractions and these compounds are likely oral drug candidates.
