• 作者：Dongyan  ; Guo^a ;   ; ^b ; Junzhi  ; Wang^a ; Xingqin  ; Wang^a ; Huajun  ; Luo^a ; Hongqi  ; Zhang^a ; Dan  ; Cao^a ; Lei  ; Chen^a ; Nianyu  ; Huang^a ;   ; ^{hny115@126.com}
• 关键词：Rhizoma drynariae ; Naringin ; Naringenin ; Estrogenic activities ; Anti-estrogenic activities
• 刊名：Journal of Ethnopharmacology
• 出版年：2011
• 出版时间：18 November 2011
• 年：2011
• 卷：138
• 期：2
• 页码：451-457
• 全文大小：699 K

lass=""h4"">Ethnopharmacological relevance

lass=""h4"">Aim of the study

The purpose of this paper is to confirm estrogenic and anti-estrogenic activity of naringin and naringenin, and provide the basic data to further study for the dose¨Ceffect relationship and the mechanism for lns="""">Rhizoma drynariae in treatment of osteoporosis and other estrogen deficiency-related diseases.

lass=""h4"">Materials and methods

Naringin was extracted from lns="""">Rhizoma drynariae. Naringin and its metabolin naringenin were tested estrogenic and anti-estrogenic activities through the experiment of cell proliferation and uterus weight gain in mice. Their estrogen-receptor binding abilities were tested by yeast two-hybrid experiment and nuclear receptor cofactor assays (RCAS) experiment, and their possible binding sites for ER¦Â were performed by computer aided molecular docking technology.

lass=""h4"">Results

Naringin and naringenin showed significant effects on the proliferation of estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen. Induction increased proliferation as the drug concentration, and the strongest proliferation appeared at a concentration of 8.6 ¡Á 10^lns="""">? M. When estradiol (10^lns="""">?0 M) and the different concentrations of naringin or naringenin were treated at the same time, naringin and naringenin could result in antagonistic effects on estradiol-induced MCF-7 cell proliferation, but they did not significantly affect proliferation of estrogen-insensitive ER(? MDA-MB-231 cells. Naringin and naringenin exhibited higher binding capacity to estrogen receptor ¦Â (ER¦Â) than estrogen receptor ¦Á (ER¦Á) in yeast two-hybrid experiments and nuclear receptor cofactor assays (RCAS) experiment. Docking simulation between naringin/naringenin and ER¦Â were performed, and the corresponding binding free energies of naringin¨Creceptor and naringenin¨Creceptor docked complexes were ?.95 and ?0.45 kcal/mol. Hydrogen bonds were found between naringin and the amino acid residues Lys304 and His308. The oxygen atom (O11) of naringenin formed hydrogen bond to Arg346, and there may be hydrophobic space interactions between phenyl group (C13¨CC18) of naringenin and the amino acid residues Leu298, Met336, Met340, Phe356, Ile376 and Leu380.

lass=""h4"">Conclusions

Naringin and naringenin revealed a double directional adjusting function of estrogenic and anti-estrogenic activities. Both of them showed estrogenic agonist activity at low concentration or lack of endogenous estrogen. On the other hand, they also acted as estrogenic antagonists at high concentrations or too much endogenous estrogen. They produced estrogenic and anti-estrogenic effects primarily through selectively binding with ER¦Â, which could prevent and treat osteoporosis with the mechanism of estrogenic receptor agitation. This paper confirmed the estrogenic and anti-estrogenic activity of naringin and naringenin, and further studies were still essential to study their dose¨Ceffect relationship and the anti-osteoporosis mechanism for lns="""">Rhizoma drynariae in the treatment of osteoporosis and other estrogen deficiency-related diseases.