Estrogenic and anti-estrogenic activities of Cassia tora phenolic constituents.
Through an estrogenic activity bioassay-guided fractionation of the 70% ethanolic extract of Cassia tora seeds two new phenolic triglucosides, torachrysone 8-O-[beta-D-glucopyranosyl(1-->3)-O-beta-D-glucopyranosyl(1-->6)-O-beta-D-glucopyranoside] (1) and toralactone 9-O-[beta-D-glucopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranoside] (2), along with seven known compounds were isolated. The structures of the new compounds were elucidated on the basis of spectroscopic and chemical evidence. The estrogenic activity of the fractions and the isolated compounds were investigated using the estrogen-dependent proliferation of MCF-7 cells. In addition, the yeast two hybrid assay expressing estrogen receptor alpha (ERalpha) and beta (ERbeta) and the ERalpha competitor screening assay (ligand binding screen) were used to verify the binding affinities of the isolated compounds to ER. Furthermore, a naringinase pre-treatment of the 70% alcoholic extract of Cassia tora seeds resulted in a significant increase in its estrogenic activity. From the naringinase pre-treated extract six compounds were isolated, among which 6-hydroxymusizin and aurantio-obtusin showed the most potent estrogenic activity, while torachrysone, rubrofusarin and toralactone showed a significant anti-estrogenic activity. Finally, the structure requirements responsible for the estrogenic activity of the isolated compounds were studied by investigating the activity of several synthetic compounds and chemically modifying the isolated compounds. The basic nucleus 1,3,8-trihyroxynaphthalene (T(3)HN) was found to play a principal role in the binding affinity of these compounds to ER.
El-Halawany
Ali Mahmoud
AM
Institute of Natural Medicine, University of Toyama, Japan.
Chung
Mi Hwa
MH
Nakamura
Norio
N
Ma
Chao-Mei
CM
Nishihara
Tsutomu
T
Hattori
Masao
M
D002366:Cassia / Q000737:chemistry*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000187:drug effects*; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D009284:Naphthols / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D048789:Phytoestrogens / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
C522206:1,3,8-trihydroxynaphthalene; D047628:Estrogen Receptor alpha; D009284:Naphthols; D010636:Phenols; D048789:Phytoestrogens; D010936:Plant Extracts; D011753:Pyrones; D012717:Sesquiterpenes; D000431:Ethanol; C005505:toralactone; C015497:rubrofusarin