Effects of Heliotropium indicum L.on Uterine Involution and Its Underlying Mechanisms:An in vivo and in vitro Study

Objective:To investigate the effect of Heliotropium indicum L.(H.indicum L.)on uterine involution and its underlying mechanisms in both in vivo and in vitro study.Methods:For in vivo studies,postpartum rats were randomly divided into 2 groups(n=24 for each):control group and treated group which were orally and daily administered with ethanolic extract of H.indicum L.(250 mg/kg body weight)until day 5 of postpartum.Uteri were collected for analysis of weight,cross-sectional area,collagen cross-sectional area,and collagen content on postpartum day 1,3,and 5(n=8 for each)from both groups.Blood samples were collected for hepatotoxicity and 17?-estradiol(E_(2))measurement.For in vitro studies,the extract effects on uterine contraction at half maximum effective concentration of 2.50 mg/mL were studied in organ bath system for at least 20 min.Results:Uterine parameters were significantly decreased after treated with extract of H.indicum L.(P<0.05).H.indicum L.extract significantly accelerated the reduction of those parameters and significantly decreased E_(2)(P<0.05).The extract facilitated uterine involution with no hepatotoxicity.H.indicum L.extract significantly stimulated uterine contraction(P<0.05)and synergized with oxytocin,prostaglandin and its precursor,linoleic acid.By investigating the different sequencing of the extract with the additional stimulants(added before or after),the two showed antagonistic effects,but still showed potentiated force when compared with control(without the stimulants).Conclusions:The underlying mechanisms by which H.indicum L.facilitated uterine involution might be due to reducing E_(2)which induces collagenase activity,leading to decreases in uterine weight and size and stimulating uterine contraction.Our study provides new findings for future drug development for facilitating uterine involution with H.indicum L.

Therapeutic Potential of Thunbergia laurifolia L.Extract in Gestational Diabetes Mellitus:Insights from a Rat Model

Objective:To assess the effects of Thunbergia laurifolia L.extract(TLE)on gestational diabetes mellitus(GDM)in a rat model.Methods:Thunbergia laurifolin L.leaves were subjected to ethanolic extraction.In vivo study,50 pregnant rats were randomly divided into 5 groups(10 for each):non-GDM group,GDM induced by streptozotocin(STZ,60 mg/kg i.p.),metformin(MET)100 mg/kg,TLE 50,and 500 mg/kg groups.Administration was performed on gestation day 7 until term(day 21).The effects of TLE on blood glucose,insulin levels,lipid profiles,liver enzymes,and maternal performances were assessed.In in vitro study,the effect of TLE was examined using the organ bath for uterine force measurement.Results:In in vivo study,TLE significantly reduced blood glucose as compared to GDM(P<0.05)with gradually increased insulin level.This effect was consistent with islets of Langerhans restoration.Histologically,the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM(P<0.05).Additionally,TLE significantly reduced total cholesterol,triglyceride,and alanine transaminase levels(P<0.05).Intriguingly,TLE also led to a notable augmentation in gravid uterus size,live fetuses count,and implantation numbers,while significantly reducing the post-implantation loss rate associated with fetal classification(P<0.05).Thus,GDM improvements were close to those produced by MET.In in vitro study,TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility(half-maximal inhibition concentration=1.2 mg/L).This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions.When combined with its major constituent,rosmarinic acid,TLE produced an enhanced inhibitory effect(P<0.05).Conclusions:TLE ameliorated blood glucose levels,enhanced uterine muscular structure,and improved maternal and fetal performance in GDM.TLE also displayed tocolytic properties.These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.