Erythrina excelsa exhibits estrogenic effects in vivo and in vitro and is cytotoxic on breast and colon cancer cell lines.

CONTEXT: Eythrina excelsa Baker (Fabaceae) is a medicinal plant used to treat various ailments including those of the female genital tract. OBJECTIVE: The objective of this study is to investigate the estrogenic and cytotoxic effects of the ethanol extract of the stem bark of E. excelsa. MATERIALS AND METHODS: Erythrina excelsa was evaluated in vitro using the yeast estrogen screen (YES). The extract was then tested in a 3-day uterotrophic assay on ovariectomised Wistar rats at doses of 50 and 100 mg/kg BW/d. Cytotoxic effects were assessed on breast (MCF-7) and colon (HT-29) cancer cell lines using the MTT cell viability assay. Additionally, a LC-PDA-ESI (+)-HRMS and HRMS/MS method was developed and applied for the identification of representative secondary metabolites scaffolds in the extract. RESULTS: In the YES, the extract stimulated the transactivation of the estrogen receptor in a dose-dependent manner with an EC50 value of 1.8 µg/mL. In rats, E. excelsa increased uterine wet weight, uterine epithelial height, and the mRNA expression of estrogen-responsive genes in the uterus and liver at 50 whereas at 100 mg/kg BW/d anti-estrogenic effects were observed. In the MTT-assay, a dose-dependent decrease of the viability of both cell lines was observed with EC50 values of 13.6 µg/mL (MCF-7) and 27.7 µg/mL (HT-29). The phytochemical analysis revealed that the extract is rich in isoflavonoids, mainly prenylated and pyran-derivatives thereof. CONCLUSION: Erythrina excelsa is rich in prenylated and pyran-substituted isoflavonoids, exhibits estrogenic/anti-estrogenic and cytotoxic effects and warrant sufficient interest for deeper investigations.

Physical activity and estrogen treatment reduce visceral body fat and serum levels of leptin in an additive manner in a diet induced animal model of obesity.

Estrogen replacement and physical activity have been demonstrated to reduce the risk to develop a metabolic syndrome in postmenopausal women. In this study we investigate the combined effects of endurance training and estrogen substitution in a rat animal model of diet induced obesity. Effects on lipid and glucose metabolism were evaluated. Ovariectomized (OVX) or sham-operated (SHAM) female Wistar rats were fed with a high fat diet (HF) for 9 weeks. After 3 weeks of overnutrition the OVX rats either remained sedentary, performed treadmill training, received 17ß-Estradiol (E(2)), or combined treatment. The OVX rats had a greater increase in body weight and serum levels of cholesterol, triglyceride and low-density lipoprotein cholesterol (LDL). These parameters could be reduced by E(2) and more effectively E(2) in combination with exercise. Also the increase of visceral body fat and leptin could be improved by E(2) and exercise. This combination showed synergistic effects. Serum levels of insulin could be reduced by exercise training, E(2) substitution revealed no significant changes. Our results indicate that ovariectomy increases the susceptibility to develop obesity. In addition they show that the combination of hormone replacement therapy (HRT) and physical activity may influence parameters related to lipid metabolism positively in an additive manner. The results of this study provide evidence that the combination of HRT with physical activity could be a very effective strategy to prevent the development of a metabolic syndrome induced by overnutrition.

Oral treatment with genistein reduces the expression of molecular and biochemical markers of inflammation in a rat model of chronic TNBS-induced colitis.

BACKGROUND: Inflammatory bowel disease (IBD) in humans has a high incidence in Europe and the USA, whereas in East Asia, incidence has been historically low. The risk of IBD appears to increase in Asian immigrants adopting western lifestyles, suggesting a strong link of environmental/dietary factors in the development of IBD. Exposure to high levels of isoflavones such as genistein (Gen) in traditional East Asian diets has been associated with a decreased risk of developing breast cancer and may also be beneficial for the prevention of IBD. AIM: In this study, the effect of orally administered genistein on the inflammatory response in the TNBS-induced chronic colitis rat model was investigated. METHODS: Eighteen male Wistar rats, aged 12 weeks, were randomized to one of three groups (n = 6). Two groups received a 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema, then were treated daily by oral gavage with either Gen (100 mg/kg b.w.) or vehicle, for 14 days. The last group served as a control group, not receiving the TNBS enema. At the end of the 14 days, animals were killed and tissues collected. Molecular and biochemical inflammatory markers in the colon, specifically cyclooxygenase-2 (COX-2) and myeloperoxidase (MPO), were analyzed. In addition, to assess the efficacy of Gen treatment, relative wet weights of the accessory sexual organs, specifically prostate and the seminal vesicle, were compared between the groups treated or not with Gen. RESULTS: Wet weights of both prostates and seminal vesicles were significantly (P < 0.01) reduced upon Gen administration. In the colon, expression of COX-2 mRNA and protein was reduced (P < 0.05) in the Gen treatment group, as compared to the control group, whereas there was no significant inhibitory effect of Gen on the expression of proliferating cell nuclear antigen. In Gen treated animals colon wet weight was not altered, however a decrease in MPO activity (P < 0.01) was seen. CONCLUSION: These results may provide evidence that oral administration of Gen exerts beneficial anti-inflammatory effects in a rodent model of TNBS-induced chronic colitis. While the sample size of this study was small, it nevertheless might encourage the realization of larger blinded randomized controlled studies for the proof of concept.

In utero and postnatal exposure to a phytoestrogen-enriched diet increases parameters of acute inflammation in a rat model of TNBS-induced colitis.

Inflammatory bowel disease (IBD) is very common in Europe and USA. Its incidence in East Asia has been traditionally low, albeit the risk of IBD increases in Asian immigrants adopting western lifestyles, suggesting a strong role of environmental/dietary factors in IBD. A lifelong exposure to phytoestrogen-rich diets has been associated with a decreased risk of developing breast cancer and might also be protective against IBD. We studied the influence of in utero and postnatal exposure to a phytoestrogen (PE)-rich diet on acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were exposed in utero and postnatally to high (genistein: 240 microg/g feed; daidzein: 232 microg/g feed) or very low levels (genistein and daidzein <10 microg/g feed) of phytoestrogen isoflavones fed to pregnant dams with the diet and throughout nursing. After weaning, the offspring had free access to these diets. At the age of 11 weeks, colitis was induced with an enema of TNBS. After 3 days, animals were sacrificed and tissues were collected for histological evaluation and analysis of molecular markers of inflammation. Animals kept on a PE-rich diet (PRD) had higher colon weights than animals on low PE-levels (PDD), suggesting enhanced acute inflammation by phytoestrogens. This result was supported by histological findings and by analysis of myeloperoxidase activity. Interestingly, relative mRNA and protein expression of cyclooxygenase-2 (COX-2) were modulated in rats on PRD, providing evidence that COX-2, the inducible isoform of the enzyme, is involved in the management of colonic inflammation. Our results suggest that early-in-life exposure to PE might not protect against the development of IBD but enhances the extent of acute inflammation.