Improvements of insulin resistance in ovariectomized rats by a novel phytoestrogen from <it>Curcuma comosa </it>Roxb

<p>Abstract</p> <p>Background</p> <p><it>Curcuma comosa </it>Roxb. (<it>C. comosa</it>) is an indigenous medicinal herb that has been used in Thailand as a dietary supplement to relieve postmenopausal symptoms. Recently, a novel phytoestrogen, (3<it>R</it>)-1,7-diphenyl-(4<it>E</it>,6<it>E</it>)-4,6-heptadien-3-ol or compound 049, has been isolated and no study thus far has investigated the role of <it>C. comosa </it>in preventing metabolic alterations occurring in estrogen-deprived state. The present study investigated the long-term effects (12 weeks) of <it>C. comosa </it>hexane extract and compound 049 on insulin resistance in prolonged estrogen-deprived rats.</p> <p>Methods</p> <p>Female Sprague-Dawley rats were ovariectomized (OVX) and treated with <it>C. comosa </it>hexane extract (125 mg, 250 mg, or 500 mg/kg body weight (BW)) and compound 049 (50 mg/kg BW) intraperitoneally three times per week for 12 weeks. Body weight, food intake, visceral fat weight, uterine weight, serum lipid profile, glucose tolerance, insulin action on skeletal muscle glucose transport activity, and GLUT-4 protein expression were determined.</p> <p>Results</p> <p>Prolonged ovariectomy resulted in dyslipidemia, impaired glucose tolerance and insulin-stimulated skeletal muscle glucose transport, as compared to SHAM. Treatment with <it>C. comosa </it>hexane extract and compound 049, three times per week for 12 weeks, markedly reduced serum total cholesterol and low-density lipoprotein levels, improved insulin sensitivity and partially restored uterine weights in ovariectomized rats. In addition, compound 049 or high doses of <it>C. comosa </it>hexane extract enhanced insulin-mediated glucose uptake in skeletal muscle and increased muscle GLUT-4 protein levels.</p> <p>Conclusions</p> <p>Treatment with <it>C. comosa </it>and its diarylheptanoid derivative improved glucose and lipid metabolism in estrogen-deprived rats, supporting the traditional use of this natural phytoestrogen as a strategy for relieving insulin resistance and its related metabolic defects in postmenopausal women.</p

Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats

BACKGROUND: The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats. METHODS: Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth-restricted rats at 6 and 12 months of age; sex steroids at 12 months. RESULTS: Glucose intolerance was present at 6 months of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth-restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose and testosterone at 12 months of age (P<0.05). Insulin release in response to a glucose challenge was blunted in conjunction with a reduction in protein expression of pancreatic glucose transporter type 2 and estrogen receptor alpha at 12 months of age in female growth-restricted rats (P<0.05). CONCLUSION: This study demonstrated that slow fetal growth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift towards testosterone excess at 12 months of age in female growth-restricted rats