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A pinboard by
AKM Moyeenul Huq

I am a Pharmacist. completed my Bachelor in Pharmacy and Masters in Pharmaceutical Technology. I am from Bangladesh. I used to be a Lecturer at the department of Pharmacy, Southern University Bangladesh. Currently, doing PhD at UKM, Malaysia.

I like to spend my time with my family. I have a lovely wife and a beautiful son. I like to eat and travel. I like to play cricket, table tennis and badminton.

PINBOARD SUMMARY

Phytoestrogenic activity of Mimosine- a phenyl alanine alkaloid

Hormone replacement therapy (HRT) has been generally used in postmenopausal symptoms in women caused by lack of endogenous oestrogen. However, due to its increased concern about the potential risks of breast and endometrial cancer there is increased demand of natural oestrogenic agents with lesser side effects. Mimosine is a phenylalanine class of alkaloid. It has been reported that, another phenylalanine alkaloid capsaicine and its analogues possess estrogenic activity. Therefore, this study was designed to investigate the oestrogen like activity of mimosine by using in vitro assays on ER positive MCF-7 and in silico models. Cell viability by cellular count and MTT cell proliferation assays were performed using the oestrogen-dependent MCF-7 breast cancer cells. The regulation of oestrogen marker TFF1 and PGR genes expression were also studied. The binding ability of mimosine to ERα was predicted by in-silico docking method. The results indicated that mimosine caused significant cell proliferation (p < 0.05) and increased cellular viability at 0.1 µM concentration. It also increased the expression of both TFF1 (p < 0.01) and PGR mRNA levels (p < 0.05), while co-treatment with antiestrogen tamoxifen significantly decreased the MCF-7 cell proliferation (p < 0.001) indicating ER mediated effect of mimosine. The docking result showed moderate interaction with ERα binding site as compared to estradiol. The results indicate the oestrogenicity of mimosine for the first time and suggest that, it can be further studied and developed as an alternative to HRT for postmenopausal women.

6 ITEMS PINNED

Estrogenic activity of griffonianone C, an isoflavone from the root bark of Millettia griffoniana: regulation of the expression of estrogen responsive genes in uterus and liver of ovariectomized rats.

Abstract: Griffonianone C (Griff C) is an isoflavone produced by Millettia griffoniana (Bail) and exhibits estrogenic properties in in vitro reporter gene assays. In order to validate its estrogenic potency in vivo, we administered subcutaneously Griff C (2, 10, or 20 mg/kg/d BW), 17beta-estradiol (10 microg/kg/d BW) as positive control, and a vehicle control to ovariectomized Wistar rats. After three consecutive days of treatment animals were sacrificed 24 hours after receiving the last dose. The uteri and livers were excised, weighed and stored for mRNA expression analysis by real-time PCR. The uterine wet weight was not significantly increased by Griff C, although there was a trend towards an increase. In contrast, 17beta-estradiol increased uterine wet weight 4.5-fold in comparison to the vehicle control. However, as revealed by real-time PCR Griff C affected the expression of estrogen-responsive genes in uterus and liver of ovariectomized rats. E2 induced a 550-fold stimulation of uterine C3 mRNA expression. Griff C at the dose 20 mg/kg/d BW caused a 50-fold up-regulation of complement C3 mRNA compared to the control. A significant increase in calcium binding protein 9-kilodalton mRNA expression was observed in the uterus of ovariectomized rats treated with E (2) (41-fold versus control) or 20 mg/kg/d BW of Griff C (25-fold versus control). In contrast, the expression of clusterin and progesterone receptor in the uterus was strongly decreased by both E2 and Griff C at the highest dose. We also found a repression of clusterin mRNA in the liver while carbonic anhydrase 2 and major acute phase protein were slightly up-regulated. In conclusion, Griff C showed a clear estrogenic action on uterine and hepatic tissues of ovariectomized rats, although its effect was less than the effect of estradiol. This suggests that some of the biological effects attributed to Millettia griffoniana are probably related to estrogen-mediated function.

Pub.: 09 May '07, Pinned: 18 Jul '17

In vitro estrogenic activity of two major compounds from the stem bark of Erythrina lysistemon (Fabaceae).

Abstract: Plant-derived estrogen-like compounds, so called phytoestrogens, are given much attention due to their potential therapeutic use. In our previous work the ethylacetate extract of Erythrina lysistemon stem bark showed estrogenic effects on cell culture systems and ovariectomized Wistar rats. Using classical chromatographic methods, two constituents of Erythrina lysistemon have been isolated, referred to here as compounds 1 (alpinumisoflavone) and 2 (abyssinone V-4'-methyl-ether), and their structures successfully determined using spectroscopic techniques. To test their binding affinity, the ligand binding assay has been used on estrogen α receptor, and estrogen β receptor. Furthermore, transactivation assay in stably or transiently transfected human osteosarcoma (U2OS-estrogen α receptor and estrogen β receptor) cells were used to examine their estrogenic activity. The regulations of some estrogen receptor target genes were also investigated. Both compounds bind to estrogen α and β receptors. They significantly increased luciferase activity in a dose-dependent manner and induced the endogenous estrogen receptor-estrogen response element (ERE) interaction in U2OS-estrogen α receptor and estrogen β receptor cells. In contrast, when co-treated with E2, compound 2 did not antagonize E2 activity in both systems whereas, 1 significantly suppressed E2 activity despite its low binding affinity to estrogen β receptor. This result suggests a non-competitive mechanism. Both compounds also altered the expression of estrogen receptor target genes such as growth regulation by estrogen in breast cancer 1 (GREB1) and Cyclin D1 in breast cells. These results suggest that compounds 1 and 2 endow estrogenic activity and may be the active principles of Erythrina lysistemon.

Pub.: 15 Nov '11, Pinned: 18 Jul '17

Estrogenic activity of isoflavonoids from the stem bark of the tropical tree Amphimas pterocarpoides, a source of traditional medicines.

Abstract: Various preparations of the African tree Amphimas pterocarpoides Harms are traditionally used to treat endocrine- related adverse health conditions. In the ovariectomized rat, the enriched in phenolics fraction of the methanol extract of stem bark of A. pterocarpoides acted as vaginotrophic agent of considerably weaker uterotrophic activity compared to estradiol. Evaluation of the fraction and 11 isoflavonoids isolated therefrom using Ishikawa cells and estrogen receptor (ER) isotype-specific reporter cells suggested that the estrogenic activity of the fraction could be attributed primarily to daidzein and dihydroglycitein and secondarily to glycitein. The potency-based selectivity of daidzein, dihydroglycitein and glycitein for gene expression through ERβ versus ERα, expressed relative to estradiol, was 37, 27 and 20, respectively. However, the rank order of relative-to-estradiol potencies of induction of alkaline phosphatase in Ishikawa cells, a reliable marker of estrogenic activity, was daidzein>dihydroglycitein>glycitein. The considerably higher estrogenic activity of dihydroglycitein compared to glycitein could be attributed to the partial agonist/antagonist activity of dihydroglycitein through ERβ. Calculation of theoretical free energies of binding predicted the partial agonism/antagonism of dihydroglycitein through ERβ. The fraction and the isolated isoflavonoids promoted lactogenic differentiation of HC11 mammary epithelial cells at least as effectively as premenopausal levels of estradiol. This data suggests that the estrogenic activity of the fraction likely depends on the metabolism of glycitein to dihydroglycitein; that the fraction could exert vaginotrophic activity likely without challenging endocrine cancer risk more than estrogen-alone supplementation; and that the fraction's safety for the reproductive track warrants a more detailed evaluation.

Pub.: 27 Dec '15, Pinned: 18 Jul '17