Anti-implantation Activity Research Articles

In vivo evaluation of substituted 2,3-diaryl acrylophenone amide derivatives as anti-implantation agents

A series of substituted 2,3-diaryl acrylophenone amide derivatives was evaluated for their anti-implantation activity in mature female Sprague-Dawley rats. Compounds 11, 14, 15, and 19 showed significant activity in preventing implantation in rats at 10 mg kg−1.

Synthesis and structure guided evaluation of estrogen agonist and antagonist activities of some new tetrazolyl indole derivatives

Several regioisomeric tetrazolyl indole derivatives with structurally modified alkyl substituents at the tetracyclic indole nitrogen containing N-ethyl amino tetrazole moiety have been synthesized and screened for their ER binding affinity, agonist (estrogenic), antagonist (antiestrogenic) and anti-implantation activities. N-2 regioisomers were found to be moderately antagonists and one compound showed 100% contraceptive efficacy at 10 mg/kg dose. Molecular docking studies carried out in comparison to estradiol and raloxifene showed different binding modes of the two regioisomers to the binding site.

Contraceptive and hormonal properties of the stem bark of Dysoxylum binectariferum in rat and docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction

Background This study was aimed to investigate the pregnancy interceptive activity of the stem bark of Dysoxylum binectariferum Hook. f. administered during the pre- and peri-implantation periods and immediately after implantation by oral route in adult female Sprague–Dawley rats. Study Design Ethanolic extract and its fractions were administered to female rats on Days 1–10, Days 1–7, Days 1–5 or Day 1 postcoitum by oral route. At autopsy on Day 12, the number and status of corpora lutea and implantations were recorded. For estrogenic activity, ovariectomized immature rats received the test extract or the vehicle once daily for 3 days and at autopsy on Day 4, uterine weight and status of vaginal opening and extent of vaginal cornification were recorded. For antiestrogenic activity, the extract was administered along with ethinyl estradiol. Docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction, to estrogen receptor (ERα) was conducted using AutoDock 3.0.5 on a Linux workstation. Results The ethanolic extract intercepted pregnancy in rats at a daily dose of 500 mg/kg on Days 1–7 postcoitum. On fractionation, the activity was localized in the chloroform fraction, which inhibited pregnancy in all females at the 35-mg/kg dose on Days 1–7, at the 50-mg/kg dose on Days 1–5 or at the single 300-mg/kg dose on Day 1 postcoitum. Chromatography of this fraction yielded an alkaloid, rohitukine, which prevented pregnancy at the 10-mg/kg dose administered on Days 1–7 but was partially (45%) effective at this dose when administered during the entire preimplantation period and ineffective even at 10 times this dose when administered only on Day 1 postcoitum, except that there was a significant reduction in implantation number in pregnant females. While the active chloroform soluble fraction was devoid of any estrogen agonistic or antagonistic properties, a mild uterotropic effect without induction of premature opening of vagina or cornification of vaginal epithelium was observed in rohitukine at the 10-mg/kg dose. Rohitukine, with an almost similar molecular size (mol. wt. 305) as 17β-estradiol, fits ideally into the hydrophobic pocket of ER. While it does not appear to simultaneously interact with GLU353, ARG394 and HIS524 as estradiol to elicit frank estrogenic response, different conformations of the ligand or its metabolite(s) might acquire geometry with phenolic groups at C-3′, C-5 and C-7 positions disposed in a fashion to interact with active site(s) of ER, which might be responsible for its contraceptive and/or weak uterotropic effects. The absence of a basic side chain directed toward the antiestrogen binding site (ASP351) on the receptor appears to be responsible for the lack of any estrogen antagonistic activity. Conclusions Findings demonstrate the antifertility activity of the ethanolic extract of D. binectariferum, its chloroform soluble fraction and rohitukine. Efforts are being made to enhance the anti-implantation activity of rohitukine by structural modifications.

Antifertility activity of hydro alcoholic extract of Moringa concanensis Nimmo: An ethnomedicines used by tribals of Nilgiris region in Tamilnadu

In the present study, the hydro alcoholic extract of Moringa concanensis and their different fractions were evaluated for it's anti implantation, abortifacient, estrogenic and antiestrogenic activity. Hydro alcoholic extract of Moringa concanensis has showed potent antiimplantation and abortifacient activity at 200 mg/kg and 400 mg/kg respectively and marked estrogenic activity when administered individually and anti estrogenic activity was observed when administered along with ethinyl estradiol (1 <TEX>${\mu}g/rat/day$</TEX>) as well as their different fractions of Moringa concanensis showed significant antiimplantation and abortifacient activity at 100 mg/kg. Moreover, all tested fractions showed significant anti estrogenic activity when administered simultaneously with ethinyl estradiol.

Pre-coital and post-coital anti-implantation and abortifacient activities of Aristolochia bracteolata Lam. aerial parts

The ethyl acetate soluble fraction of the ethanolic extract of Aristolochia bracteolata was tested for pre-coital and post-coital anti-implantation and abortifacient activities in female albino rats. In the pre-coital study, the treatment at 20 and 40 mg/kg body weight showed significant and dose-related anti-implantation and abortifacient properties. In the post-coital studies at 20, 30 and 40 mg/kg body weight doses, similar results were observed. The total antifertility activity at 40 mg/kg body weight was found to be comparable to that of standard ethinyl estradiol given for the similar period. The plant merits further investigation to prove the mechanism of action and to isolate its phytoconstituents.

Estrogenic and pregnancy interceptory effects of &lt;i&gt;Achyranthes aspera&lt;/i&gt; Linn. root

Achyranthes aspera Linn. (Amaranthaceae) is an abundant indigenous herb in India. It is traditionally being used as an abortifacient. Four successive solvent extracts of the root were screened for antifertility activity in female albino rats. The chloroform and ethanol extracts exhibited 100% anti-implantation activity when given orally at 200 mg/kg body weight. Both the extracts at the dose of 200 mg/kg body weight also exhibited estrogenic activity. Histological studies of the uterus were carried out to confirm this estrogenic activity.

Antiimplantation activity of the ethanolic root extract of Momordica cymbalaria Fenzl in rats

<b>Objective</b> : To evaluate the antiimplantation activity of the ethanolic root extract of Momordica cymbalaria Fenzl.<br><b>Materials and Methods</b> : The acute oral toxicity study was performed according to the OPPTS guidelines. The ethanolic root extract was investigated for antiimplantation, estrogenic and progestrogenic activities at doses of 250 and 500 mg/kg body weight. Antiimplantation activity was studied on successive stages of embryogenesis. Estrogenic studies were carried out by examining uterine weight, histoarchitecture of uterus, vaginal cornification, uterine content of glucose, cholesterol and alkaline phosphatase levels in immature rats. Progestrogenic activity assay was performed by pregnancy maintenance in rats and Clauberg's test (endometrial proliferation assay) in immature rabbits.<br><b>Results</b> : Both doses of the ethanolic root extract exhibited highly significant (P < 0.001) antiimplantation activity. However, an investigation of the estrogenic activity did not show any increase in uterine weight or vaginal cornification. The histoarchitecture (uterotrophic changes) such as thickness of endometrium and height of endometrial epithelium was unaltered in treated rats. There were no increases in the uterine content of glucose, cholesterol or alkaline phosphatase levels when compared with the control group. Pregnancy was not maintained in the pregnancy maintenance test for progestrogenic activity. Uterine proliferation was not seen in Clauberg's test (endometrial proliferation assay) for progestrogenic activity in immature rabbits.<br><b>Conclusion</b> : The ethanolic root extract of Momordica cymbalaria Fenzl exhibited antiimplantation activity but this is not due to estrogenic or progestrogenic activities.

Antifertility effect of aqueous and ethanol extracts of the leaves and roots of Asparagus africanus in rats.

Asparagus africanus is claimed to have use in reproductive related health problems in some areas of Ethiopia. To study the potential antifertility effect of the aqueous and ethanol extracts of the leaves and roots of Asparagus africanus in rats. Water and ethanol extracts were given by gavages to rats in the in vivo test at a dose of 300 mg/kg of body weight, and rat uterine tissue were used for the in vitro test at different concentrations. The aqueous extracts of the leaves and the roots showed an anti-implantation activity of 70% and 77%, respectively, while the ethanol extracts of the leaves and roots showed 48% and 61%, respectively. The antifertility activities of the aqueous and ethanol extracts were 40% (for leaves), 60% (for roots) and 20% (for leaves), 40% (for roots), respectively. All the extracts have resulted in significant (P< 0.05) reduction in the number of implants as compared with their respective controls. Each extract potentiated acetylcholine induced uterine contractions in a concentration dependent manner significantly (P< 0.05). The results obtained in this study suggest that the leaves and roots of this plant may possess hormonal properties that can modulate the reproductive function of the experimental rats.

Post-coital antifertility activity of Achyranthes aspera Linn. root

Achyranthes aspera Linn. (Amaranthaceae) is an abundant indigenous herb in India. It is traditionally being used as an abortifacient. The ethanol extract of the root was screened for antifertility activity in proven fertile female albino rats at 200 mg/kg body weight and given orally on days 1–7 of pregnancy. The ethanol extract exhibited 83.3% anti-implantation activity when given orally at 200 mg/kg body weight. The rats, which continued their pregnancy, did not deliver any litters after their full term. Hence the combined antifertility (anti-implantation and abortifacient) activity of ethanol extract was 100%. The results suggest that the ethanol extract possess both anti-implantation and abortifacient activity. The ethanol extract also exhibited estrogenic activity tested in immature ovariectomised female albino rats. Histological studies were carried out to confirm this.

A potential anti-implantation and spermicidal strategy: Putative derivatives of nonoxynol-9 and anti-inflammatory agents and their spermicidal activity

Objectives We report the synthesis of novel ester derivatives of nonoxynol-9, an approved spermicidal agent, using the non-steroidal inflammatory drugs (NSAIDs) ibuprofen and indomethacin. Indomethacin has previously been shown to inhibit the implantation of the fertilised ovum into the uterus wall of pregnant rats. It is proposed that nonoxynol-9, in combination with a non-selective NSAID may exhibit both anti-implantation and spermicidal properties.Methods Both novel derivatives and nonoxynol-9 were then tested on boar spermatozoa in order to establish if spermicidal activity was retained following the esterification.Results The results showed that both the ibuprofen and indomethacin derivatives enabled complete cell death of boar spermatozoa at a concentration of 100 µg ml−1, which is comparable to nonoxynol-9 at the same concentration.Conclusions These results indicate that NSAID derivatives of nonoxynol-9 retain the activity of the parent molecule and may have other advantages associated with the molecular incorporation of the NSAID moieties and their anti-implantation activity.

Evaluation of some indigenous plant extracts for antiimplantation activity in albino rats

In the present investigation twelve indigenous medicinal plants have been screened for their antiimplantation activity in albino rats. The plant material was subjected for soxhlation successively and separately from non-polar solvents to polar solvents i.e., petroleum ether benzene and ethanol. Out of these three extracts the petroleum ether extract of seeds of Citrus medica, aerial part of Oxalis corniculata and Tinospora cardifolia have showed maximum antiimplantation activity. Ethanol extract of leaves of Cardiospermum helicacabum, roots of Echinops echinatus, leaves of Melia azedarach, seeds of Momordica charantia and bark of Terminalia bellirica have shown maximum antiimplantation activity amongst the three extracts of each plant material screened. Though all the three extracts of seeds of Annona squamosa and leaves of Zizyphus jujube screened for antiimplantation activity, no extract has showed any loss in implantation. The details of the results obtained are discussed.

Synthesis and anti‐Implantation Activity of Novel Non‐Steroidal 4,5‐Disubstituted 2,3,4,5‐Tetrahydro‐1‐benzoxepines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Blastocyst implantation failure in mice due to “nonreceptive endometrium”: endometrial alterations by Hibiscus rosa-sinensis leaf extract

Many plants are known to possess antifertility activity. However, limited attempts have been made to scientifically evaluate these claims. Hibiscus rosa-sinensis flowers have been shown to possess antifertility and abortifacient activity. In this report, antiimplantation activity of water extract of leaves of H. rosa-sinensis was investigated. Pregnant female mice were dosed with extract (100 mg/kg body weight) from days 1 to 6 of pregnancy. No implantation sites were observed in treated animals when they were surgically opened on day 15 of pregnancy. Biochemical and biophysical alterations were observed in the endometrium in treated animals, especially on day 5, at 4:40 a.m., the day of implantation. A sharp increase in superoxide anion radical and a sharp fall in superoxide dismutase (SOD) activity, as seen in the endometrium from control animals, were altered in treated animals. The extract also exhibited antiestrogenic activity, as judged by increase in uterine weight. The physiological alterations induced by water extract of H. rosa-sinensis are discussed.

2,3,4,5- Tetrahydro- 1-Benzoxepines a Novel Class of Anti-Implantation Agents

5- Substituted 2,3,4,5- Tetrahydro- 1-benzoxepine derivatives have been synthesized as novel antiimplantation agents. The synthesized compounds were evaluated for their anti-implantation activity in mature female Sprague-Dawley rats. The most active compounds in this series 10d and 11d, are 67% active in preventing implantation in rats at 10 mgkg-1 dose. We also found that the other compounds of the series have lesser anti-implantation activity compared to the most potent anti-implantation drug Centchroman 5.

Synthesis and Antiimplantation Activity of New Stilbene Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Biologically Active Angularly Fused Bisaroylbenzodifurans by PTC and Solvent Free Microwave Irradiation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Non‐steroidal Pregnancy‐Terminating Agents: Design, Synthesis and Structure—Activity Relationships of 2‐Aryl‐1,2,4‐triazolo[1,5‐a]pyridine.

The syntheses and the pregnancy-terminating activity relationships of compounds -n are reported. Compounds 5b and are found to be more potent than DL-111-a known drug having effective pregnancy-terminating activity in vitro. Further research shows compounds 5b and have the same activity as DL-111 in vivo. We also found an exciting result that they have excellent anti-implantation activity after oral administration.

Antifertility activity of Derris brevipes variety coriacea

Traditional physicians in and around Kotagiri village near Ootacamund, use a mixture of powdered roots of Cassia occidentalis, Derris brevipes variety coriacea and Justicia simplex to control female fertility. A mixture of powdered roots of these three plants, powdered root of Derris brevipes variety coriacea and its ethanolic extract were screened for antifertility activity in proven fertile female rats at 200 and 600 mg/kg body weight, respectively and given orally on D 1–7 of pregnancy. Both doses of the root powder of Derris brevipes variety coriacea showed 50% anti-implantation activity and also a significant reduction in the number of litters born. The ethanolic extract exhibited 40% anti-implantation activity when given orally at 600 mg/kg body weight. The rats, which continued their pregnancy, did not deliver any litters after their full term. Hence, the combined antifertility (anti-implantation and abortifacient) activity of the ethanolic extract was 100%. The results suggest that the ethanolic extract possesses more abortifacient type effect than the anti-implantation activity. The ethanolic extract also exhibited weak estrogenic activity when given alone and tested in immature ovariectomised female albino rats. But, when given along with ethinyl estradiol, it exhibited slight antiestrogenic activity. Histological and biochemical estimations were carried out to confirm this.

Non-steroidal Pregnancy-Terminating Agents: Design, Synthesis and Structure–Activity Relationships of 2-Aryl-1,2,4-triazolo[1,5- a]pyridine

The syntheses and the pregnancy-terminating activity relationships of compounds 5a – n are reported. Compounds 5b and 5l are found to be more potent than DL-111—a known drug having effective pregnancy-terminating activity in vitro. Further research shows compounds 5b and 5l have the same activity as DL-111 in vivo. We also found an exciting result that they have excellent anti-implantation activity after oral administration.

Interaction with anti-implantation and estrogen antagonistic activities of dl-ormeloxifene, a selective estrogen receptor modulator, by tetracycline in female Sprague-Dawley rats

Among the 10 commonly used therapeutic agents investigated, concurrent oral administration of tetracycline (140 mg/kg) twice daily on Days 1–5 post-coitum (pc) interfered with the post-coital anti-implantation activity and almost completely abolished estrogen antagonistic activity of the single anti-implantation (1.5 mg/kg, orally) dose of dl-ormeloxifene administered on Day 1 pc, resulting in the occurrence of resorbed implantations in 50% of the females. However, no such interaction was evident when tetracycline was administered intramuscularly or when ormeloxifene was administered at twice its anti-implantation dose. There was no effect of ormeloxifene and/or tetracycline treatment on serum estradiol and progesterone levels, and all animals presented apparently normal corpora lutea. Ormeloxifene administered per se inhibited aminopyrine-N-demethylase (AD), glucose-6-phosphate dehydrogenase (G-6-PDH) and glutathione-S-transferase (GST) in the liver on the day of maximal endometrial receptivity, which was prevented by tetracycline co-administration. Aniline hydroxylase and AD were not detected in small intestine or uterus in vehicle control or any of the treatment groups. There was, however, no effect of ormeloxifene plus tetracycline treatment on serum total alkaline phosphatase activity. Findings suggest that interference with anti-implantation action of ormeloxifene by tetracycline might be due primarily to the almost complete abolition of its estrogen antagonistic activity at the uterine level, effected by decreased bioavailability of ormeloxifene and/or its active metabolite(s) by altered enterohepatic recirculation because of the effect on gut microflora. This might alternatively be related to an increased rate of its metabolism and elimination from the system via prevention of ormeloxifene-induced inhibition of hepatic AD, G-6-PDH, and GST, which, by effecting a decreased rate of metabolism, might be responsible for prolonged (∼120 h) duration of estrogen antagonistic/anti-implantation action of ormeloxifene in this species.