ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: In folklore medicine Ananas comosus (pineapple) is reputed to act as an abortifacient and in expectant women as a means of inducing labor. Several reports have claimed abortifacient property of A. comosus fruit (ripe or unripe). Ripe fruit has been used orally as traditional medicine in inducing abortion in Kerala state of India while the juice of unripe fruit was used for abortion in Bangladesh. However, scientific evidence supporting the efficacy of pineapple extracts in inducing uterine contractions is clearly lacking. AIM OF THE STUDY: This study investigated the pharmacological effects of different fractions of pineapple extract with a range of maturities to identify the most potent uterotonic fraction. MATERIALS AND METHODS: The ethanolic crude extracts of pineapple (edible part) were prepared and fractionated through a series of liquid-liquid partitions. Fractions were separately tested on isolated uterine muscle from pregnant SD rats and human pregnant myometrium, which were cut into strips along the longitudinal axis of uterus. The strips were mounted vertically in organ baths (37°C) and exposed to cumulative addition of fractions (0.1-10mgml-1), serotonin (0.05-5µM) and different inhibitors to delineate the mechanism of action of the active ingredients of the extract. RESULTS: Aqueous fraction (F4) possesses uterine stimulant property which was blocked by verapamil but unaffected by indomethacin, prazosin and atosiban. Notably, ketanserin (10µM) diminished the maximal contractile response induced by both F4 and 5HT by 74.3% and 92.1% respectively. CONCLUSIONS: These results may indicate the presence of 5HT or 5HT-like compound(s) and serotonergic pathways may contribute to the uterotonic activity of pineapple extract.
Subject(s)
Abortifacient Agents/pharmacology , Ananas , Muscle Contraction/drug effects , Myometrium/drug effects , Plant Extracts/pharmacology , Animals , Female , Humans , Mice , Pregnancy , Rats, Sprague-DawleyABSTRACT
Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.
Subject(s)
Decanoic Acids/therapeutic use , Dietary Fats/therapeutic use , Disease Models, Animal , Nuclear Receptor Subfamily 4, Group A, Member 1/antagonists & inhibitors , Polycystic Ovary Syndrome/diet therapy , Progesterone Reductase/antagonists & inhibitors , Promoter Regions, Genetic , Adrenal Cortex/enzymology , Adrenal Cortex/metabolism , Adrenal Glands/enzymology , Adrenal Glands/metabolism , Androgens/analysis , Androgens/chemistry , Androgens/metabolism , Animals , Cell Line , Cyclic AMP/antagonists & inhibitors , Cyclic AMP/metabolism , Decanoic Acids/metabolism , Dietary Fats/metabolism , Enzyme Repression , Female , Humans , Hyperandrogenism/etiology , Hyperandrogenism/prevention & control , Insulin Resistance , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism , Ovary/enzymology , Ovary/metabolism , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/pathology , Polycystic Ovary Syndrome/physiopathology , Progesterone Reductase/genetics , Progesterone Reductase/metabolism , Random Allocation , Rats, WistarABSTRACT
Two new types of methylcalix[4]resorcinarene-bonded stationary phases, (3-(C-methylcalix[4]resorcinarene)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MCR-HPS) and bromoacetate-substituted MCR-HPS particles (BAMCR-HPS), have been synthesized and used as chiral stationary phases for high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phases are characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. The chromatographic behavior of MCR-HPS and BAMCR-HPS was studied with several disubstituted benzenes and some chiral drug compounds under both normal phase and reversed-phase conditions. The results show that MCR-HPS has excellent selectivity for the separation of aromatic positional isomers and BAMCR-HPS exhibits excellent performance for separation of enantiomers of chiral compounds.
