ABSTRACT
Methanolic crude extract of Scoparia dulcis (CESD) was orally administered to female mice during the early gestation (day 4-day 8) at a dose of 500 mg/kg/day. It induces embryo resorption and morphological changes of fetal maternal tissue. Histomorphology was studied by routine hematoxylin eosin stain. In situ immunofluorescence localization of IGF-II using Texas red showed an ordered expression of the growth factor in the maternal decidual cells, trophoblast cells and the embryo. Western blot analysis showed a gradual increase of IGF-II from D4 to D8 of control females. In contrast, the CESD-treated females showed resorption of embryo on D8 with disorganized in situ expression and lowered IGF-II in fetal maternal tissue. The phytocompounds present in the CESD could modulate either the ER or IGF-II receptors causing reduced IGF-II expression in the target tissues which lead to the failure of embryonic growth during periimplantation.
Subject(s)
Insulin-Like Growth Factor II , Plant Extracts , Trophoblasts , Animals , Female , Mice , Pregnancy , Growth Disorders/metabolism , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/pharmacology , Trophoblasts/metabolism , Plant Extracts/pharmacology , Scoparia/chemistryABSTRACT
BACKGROUND: Scoparia dulcis Linn. is reported to be used by women of Assam and Arunachal Pradesh in northeast India for treating menstrual disorders. Scoparia dulcis contains compounds that bind with estrogen receptors (ERα and ERß) evidenced by increased PCNA in endometrial epithelium. METHODS: Crude extract was orally administered at the dose of 500 mg/kg body weight/day to the female mice (60-70 days old) in five different groups. Each group containing six females included: (I) cyclic control, (II) cyclic extract treated, (III) Ovariectomized (OVX)-vehicle treated (Control), (IV) OVX-E2 treated (V) OVX- extract treated. Extract was administered for eight days to the cyclic groups and three days to the OVX groups. PCNA was detected immunohistochemically in uterine tissues and signals were analyzed by Image J software (NIH, USA). Compounds were separated by GC-MS and identified using NIST. In silico molecular docking studies was performed with human estrogen receptors (ERα and ERß). Molecular dynamics (MD) simulations of the best interacting compound was done using gromacs. RESULTS: The results showed cell proliferation in the uterine endometrium evidenced by PCNA. Two phytocompounds, Octadecanoic acid and methyl stearate showed binding affinity with ERα and ERß. CONCLUSION: Scoparia dulcis contains compounds having binding affinity with ERα and ERß. The present study is the first report on compounds from Scoparia dulcis showing binding affinity with human estrogen receptors which may have biological effect on female reproduction.
