8-prenylnaringenin and Body-Weight

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C57Bl/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks. Fasting blood glucose and insulin tolerance tests were performed 1 week before sacrifice. At the end of the study, blood, liver and skeletal muscle were collected. Both XN and 8PN treatments prevented body weight gain; decreased glycemia, triglyceride, cholesterol and alkaline phosphatase levels; and improved insulin sensitivity. Polyphenols promoted hepatic and skeletal muscle AMP-activated protein kinase (AMPK) activation, diminishing the expression of target lipogenic enzymes (sterol regulatory element binding protein-1c and fatty acid synthase) and acetyl-CoA carboxylase activity. Moreover, both XN and 8PN treatments decreased VEGFR-1/VEGFB pathway, involved in fatty acid uptake, and increased AS160 expression, involved in GLUT4 membrane translocation. Presented data demonstrated that both XN and 8PN treatment resulted in AMPK signaling pathway activation, thus suppressing lipogenesis. Their consumption prevented body weight gain and improved plasma lipid profile, with significant improvement of insulin resistance and glucose tolerance. XN- or 8PN-enriched diet could ameliorate diabetic-associated metabolic disturbances by regulating glucose and lipid pathways.

Topics: Acetyl-CoA Carboxylase; Animals; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; fas Receptor; Flavanones; Flavonoids; Glycolysis; Insulin Resistance; Lipids; Male; Mice, Inbred C57BL; Propiophenones; Sterol Regulatory Element Binding Protein 2; Vascular Endothelial Growth Factor Receptor-1

The lack of a safe and reliable alternative to hormone therapy (HT) for treating menopausal symptoms underscores the need for alternative therapies.. The purpose of this study was to assess the in vivo estrogenic effects of the botanical dietary supplements Trifolium pratense (red clover) and Humulus lupulus (hops), and two compounds obtained from H. lupulus, isoxanthohumol and 8-prenylnaringenin (8-PN) using the ovariectomized uterotrophic adult rat model. A H. lupulus extract and a 30% isoflavone extract of T. pratense were tested at three escalating doses as was one dose of isoxanthohumol for 21d. 8-Prenylnaringenin, the major estrogen in H. lupulus, was also tested at three relevant escalating doses. In order to determine the in vivo metabolism of 8-PN, the major phases I and II metabolites were also identified. The primary outcome measure, uterus weight gain, indicated that H. lupulus and T. pratense did not have an estrogenic effect on the uterus, and none of the secondary outcome measures were positive. In contrast, there was a clear dose response when 8-PN was evaluated where the middle and high doses of 8-PN were active. 8-Prenylnaringenin in rat plasma, liver, and mammary gland was measured and the major phases I and II 8-PN metabolites were detected. Our findings suggest that while both the H. lupulus and T. pratense extracts do not have an effect on the rat uterus, 8-PN at equivalent doses to those previously used in humans did have an effect, and may therefore have a deleterious effect in women.

Topics: Animals; Body Weight; Chromatography, Liquid; Eosine Yellowish-(YS); Epithelial Cells; Estrogens; Female; Flavanones; Hematoxylin; Humulus; Mass Spectrometry; Organ Size; Plant Extracts; Rats; Rats, Sprague-Dawley; Trifolium; Uterus; Xanthones

After the heart and estrogen/progestin replacement study and the women's health initiative study, the prospect of hormone replacement therapy (HRT) on cardiovascular diseases (CVD) has changed dramatically. These findings led to various attempts to search for alternatives for classical HRT, e.g. phytoestrogens. The flavanone 8-prenylnaringenin (8-PN) was identified as a phytoestrogen with strong estrogen receptor-alpha activity. As the pituitary and the liver are targets for estrogen action, we assessed the effect of ovariectomy (OVX) and long-term treatment (3 months) with 17-beta estradiol benzoate (E(2)B) and 8-PN on pituitary and liver functions in adult OVX rats. Tested doses were 6.8 and 68.4 mg/kg body weight (BW) of 8-PN and 0.17 and 0.7 mg/kg BW of E(2)B. Our results demonstrate that 8-PN and E(2)B decreased BW and increased uterus weight. The high doses of E(2)B and 8-PN increased serum GH and decreased serum IGF-1 levels. E(2)B dose dependently decreased cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) concentrations in OVX rats. The high dose of 8-PN showed an estrogenic activity regarding cholesterol and LDL regulation but had no effect on HDL concentrations. By contrast, the low dose of 8-PN augmented HDL levels compared with intact rats. Triglyceride levels were raised in response to the high E(2)B dose but unaffected by 8-PN treatment. Taken together, 8-PN displays an anti-atherosclerotic profile that appears to be even more beneficial than the one displayed by E(2)B, and thus might demonstrate a remarkable potential for the prevention of CVD associated with estrogen deficiency.

Topics: Administration, Oral; Animals; Body Weight; Cholesterol; Chromatography, High Pressure Liquid; Estradiol; Estrogens; Female; Flavanones; Growth Hormone; Insulin-Like Growth Factor I; Lipid Metabolism; Lipoproteins, HDL; Lipoproteins, LDL; Organ Size; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Triglycerides; Uterus

Plant secondary metabolites with estrogenic activity (phyto-estrogens) have been studied in the past as a potential alternative to classical hormone-replacement therapy (HRT) in menopausal women. No final verdict on the efficacy of soy or red clover based pharmaceutical preparations has been reached despite numerous clinical studies. We have studied the novel and most potent phyto-estrogen 8-prenylnaringenin (8-PN) in adult ovariectomized rats, an established animal model to mimic hormone dependent osteoporosis in menopausal women. Our results demonstrate that 8-PN can completely protect from ovariectomy induced bone-loss while exhibiting minimal, (dose independent) trophic effects on uterus and endometrium. It is estimated that at equivalent bone protective doses of 17beta-estradiol and 8-PN, the phyto-estrogen has a 10-fold lower stimulatory effect on uterus and endometrium. The bone tissue specific effect of 8-PN was confirmed in a transgenic reporter mouse model (ERE-Luc mice). Here we also found pronounced estrogenic activity in prostate. Present results add important aspects to the pharmacological profile of 8-PN and position this compound as an interesting alternative new candidate for treatment of peri- and postmenopausal symptoms.

Topics: Animals; Body Weight; Bone Density; Epithelium; Estradiol; Female; Flavanones; Humans; Male; Mice; Mice, Transgenic; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Prostate; Rats; Rats, Sprague-Dawley; Uterus