Researcher, Indonesian Coffee and Cocoa Research Institute (ICCRI)
Assessing the potential of cocoa to substitute estrogen
Estrogen is a hormone that influences the growth of uterus. Ovariectomized rats lose their ovaries as the main source of estrogen so their uterus tends to shrink. The objective of this study was to evaluate the potency of cocoa as an estrogen substitute, which was done through an experiment that tested the influence of cocoa products on the uterus weight of ovariectomized rats. There were five treatments and in each of the treatments, six wistar rats were given the substance for three days. Four groups of treatment consisted of ovariectomized rats given cocoa extract, cocoa powder, olive oil, or estradiol valerate. The fifth group consisted of intact (non-ovariectomized) rats given water. The finding showed that the ovariectomized rats given cocoa powder and extract had higher uterus weight compared to those given only olive oil; although they were not significantly different. Correlation between the body weight and uterus weight varied across treatment groups. The rats given estradiol valerate and cocoa powder showed non-significant correlation. It was predicted that cocoa polyphenols are more potential in the lower concentration. This study concludes that even though consumption of cocoa powder and extract did not significantly induced uterus growth, cocoa is still considered having estrogenic activity by lowering the correlation between the body weight and uterus weight in ovariectomized rats.
Abstract: Pain is a common complaint among postmenopausal women. It has been postulated that vascular dysfunction caused by estrogen decline at menopause plays a key role in the initiation and progression of degradative joint disease, namely age-related osteoarthritis. We evaluated whether supplementation with resveratrol, a phytoestrogen, could improve aspects of well-being such as chronic pain that is commonly experienced by postmenopausal women.A 14-week randomized, double-blind, placebo-controlled intervention with trans-resveratrol (75 mg, twice daily) was conducted in 80 healthy postmenopausal women. Aspects of well-being, including pain, menopausal symptoms, sleep quality, depressive symptoms, mood states, and quality of life were assessed by Short form-36 at baseline and at the end of treatment. Rating scales were averaged to provide a composite score representing overall well-being. Cerebral vasodilator responsiveness to hypercapnia was also assessed as a surrogate marker for cerebrovascular function.Compared with placebo treatment, there was a significant reduction in pain and an improvement in total well-being after resveratrol supplementation. Both benefits, including measures of quality of life, correlated with improvements in cerebrovascular function.Our preliminary findings indicate potential for resveratrol treatment to reduce chronic pain in age-related osteoarthritis. Resveratrol consumption may also boost perceptions of well-being in postmenopausal women. Further investigation to elucidate underlying mechanisms is warranted.
Pub.: 30 Mar '17, Pinned: 08 Jun '17
Abstract: Diarylheptanoids from Curcuma comosa (C. comosa), Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound-092) isolated from C. comosa. The compound elicited different transcriptional activities of being estrogen agonist at low concentrations (0.1-1 μM) and antagonist at higher concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound-092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes whereas it attenuated uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound-092 promoted mouse preosteoblastic (MC3T3-E1) cells differentiation, and the related bone markers indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is the scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in post-menopausal women.
Pub.: 18 Apr '17, Pinned: 08 Jun '17
Abstract: Genistein, a major source of phytoestrogen exposure for humans and animals, has been shown to mediate neuroprotection in Alzheimer's disease and status epilepticus. In the present study, we investigated the effect of genistein on pentylenetetrazole-induced seizures in ovariectomized mice and the possible involvement of estrogenic and serotonergic pathways in the probable effects of genistein. Intraperitoneal (i.p.) administration of genistein (10 mg/kg) significantly increased the seizure threshold 30 min prior to induction of seizures 14 days after ovariectomy surgery. Administration of fulvestrant (1 mg/kg, i.p.), an estrogen receptor antagonist, completely reversed the anticonvulsant effect of genistein (10 mg/kg) in ovariectomized mice. Administration of the antagonist of serotonin receptor (5-HT3), tropisetron (10 mg/kg, i.p.), eliminated the anticonvulsant effect of genistein, whereas co-administration of m-chlorophenylbiguanide (5-HT3 receptor agonist; 1 mg/kg) and a non-effective dose of genistein (5 mg/kg) increased the seizure threshold. To conclude, it seems that estrogenic/serotonergic systems might be involved in the anticonvulsant properties of genistein.
Pub.: 26 Apr '17, Pinned: 08 Jun '17
Abstract: Recent studies suggest an anti-inflammatory activity of oxyresveratrol, a stilbene extracted from Cortex mori root used in traditional Chinese medicine that also presents estrogen-like activity. We herein tested the hypothesis that oxyreservatrol exerts an anti-inflammatory effect through its estrogenic-like function. In MCF-7 cells, oxyresveratrol significantly induced proliferation, which was accompanied with estrogen receptor (ER)-mediated transcriptional activation, increased estrogen-targeted gene expression (e.g., pS2, PGR, and CTSD), and increased ERα/β proteins. The estrogen-like effect of oxyresveratrol was reversed by the ER inhibitor ICI 182780. Strong ER-binding activities of oxyresveratrol were revealed by negative docking scores. The LPS-induced inflammatory response (e.g., upregulated IκB-α phosphorylation, NF-κB nuclear translocation, and cytokine messenger RNA expression) was significantly suppressed in an ER-dependent manner by oxyresveratrol in RAW264.7 cells. These results suggest that oxyresveratrol may function as an ER agonist and modulate NF-κB signaling.
Pub.: 10 May '17, Pinned: 08 Jun '17
Abstract: In vivo estrogenicity of genistein and its glycoside genistin is still under debate. The present study aimed to develop a physiologically based kinetic (PBK) model that provides insight in dose-dependent plasma concentrations of genistein aglycone and its metabolites and enables prediction of in vivo estrogenic effective dose levels of genistein and genistin in humans.A PBK model for genistein and genistin in humans was developed based on in vitro metabolic parameters. The model obtained was used to translate in vitro estrogenic concentration-response curves of genistein to in vivo estrogenic dose-response curves for intake of genistein and genistin.The model predicted that genistein-7-O-glucuronide was the major circulating metabolite and that levels of the free aglycone were generally low (0.5-17% of total plasma genistein at oral doses from 0.01-50 mg (kg bw)(-1) ). The predicted in vivo BMD05 (benchmark dose for 5% response) values for estrogenicity varied between 0.06 and 4.39 mg (kg bw)(-1) genistein. For genistin, these values were 1.3-fold higher. These values are in line with reported human data and show that estrogenic responses can be expected at an Asian dietary and a supplementary intake, while intake resulting from a Western diet may not be effective.The present study shows how plasma concentrations of genistein and its metabolites and estrogenic dose levels of genistein in humans can be predicted by combining in vitro estrogenicity with PBK model based reverse dosimetry, eliminating the need for human intervention studies.
Pub.: 07 Jun '17, Pinned: 08 Jun '17