Effects of long-term treatment with 8-prenylnaringenin and oral estradiol on the GH–IGF-1 axis and lipid metabolism in rats

Abstract

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-a 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-b 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 BWof 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.

Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor

“…With our experimental protocol, estrogen treatment led to increased levels not only of triglycerides and HDL, but also of LDL and total cholesterol concentrations, whereas Böttner et al reported that oral administration of estrogen decreased total cholesterol, LDL and HDL, and increased triglyceride levels in OVX rats [28]. These discrepancies may be related to the different experimental designs, in particular the different modes of estrogen administration.…”

Analytical Methods for Quantitation of Prenylated Flavonoids from Hops

“…Despite low sensitivity and poor selectivity, there have been a surprisingly large number of publications describing applications of HPLC-UV methods to the quantitation of prenylflavonoids in biological samples [21,23,64,67,69]. Except for the report by Avula et al [48] most of these studies did not show sample chromatograms, so it was not possible to determine the reliability of such data.…”

“…Except for the report by Avula et al [48] most of these studies did not show sample chromatograms, so it was not possible to determine the reliability of such data. We also note that only a few of these methods used an internal standard, despite dealing with a complex matrix and extensive sample preparation [69]. Overall, it is likely that in near future more sensitive and selective LC-MS-MS methods will replace HPLC-UV-based methods measurement of prenylflavonoids in biological samples.…”

Phytoestrogens: Naturally Occurring, Hormonally Active Compounds in Our Diet

“…107 In in vivo studies, 8PN has an anti-atherosclerotic profile which may demonstrate its potential for the prevention of estrogen deficiency associated cardiovascular diseases. 108 After long-term treatment of three months with 8PN, decreased bw and an increased uterus weight were observed, as well as with estradiol benzoate. 108 In another three month experiment, OVX rats treated with 8PN share many effects in the uterus, vagina, and mammary gland with estradiol; at the same time, differences in the mechanism of action seem to exist.…”

“…108 After long-term treatment of three months with 8PN, decreased bw and an increased uterus weight were observed, as well as with estradiol benzoate. 108 In another three month experiment, OVX rats treated with 8PN share many effects in the uterus, vagina, and mammary gland with estradiol; at the same time, differences in the mechanism of action seem to exist. 109 Other experiments in OVX rats, as a model for hormone-dependent osteoporosis, demonstrated that 8PN can completely protect from ovariectomy-induced bone loss.…”