Estrogenic and Anti-estrogenic Activities of Cassia tora Phenolic Constituents

• Published in: Chemical & Pharmaceutical Bulletin Vol. 55; no. 10; pp. 1476 - 1482
• Main Authors: El-Halawany, Ali Mahmoud, Chung, Mi Hwa, Nakamura, Norio, Ma, Chao-Mei, Nishihara, Tsutomu, Hattori, Masao
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.10.2007; Pharmaceutical Society of Japan; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: 1,3,8-trihyroxynaphthalene; 6-hydroxymusizin; Cassia - chemistry; Cassia tora; Cell Line, Tumor; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Estrogen Receptor alpha - drug effects; estrogenic activity; Ethanol - chemistry; Humans; Life Sciences & Biomedicine; Naphthols - chemistry; Naphthols - pharmacology; Pharmacology & Pharmacy; Phenols - chemistry; Phenols - pharmacology; Physical Sciences; Phytoestrogens - chemistry; Phytoestrogens - pharmacology; Plant Extracts - chemistry; Pyrones - chemistry; Pyrones - pharmacology; rubrofusarin; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; toralactone; Two-Hybrid System Techniques; SEEDS; rubrofusarin; cassia tora; toralactone; ANTHRAQUINONES; PURGATIVE CRUDE DRUGS; 1,3,8-trihyroxynaphthalene; RECEPTOR; estrogenic activity; 6-hydroxymusizin; NAPHTHOPYRONE GLYCOSIDES
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.55.1476

Through an estrogenic activity bioassay-guided fractionation of the 70% ethanolic extract of Cassia tora seeds two new phenolic triglucosides, torachrysone 8-O-[β-D-glucopyranosyl(1→3)-O-β-D-glucopyranosyl(1→6)-O-β-D-glucopyranoside] (1) and toralactone 9-O-[β-D-glucopyranosyl-(1→3)-O-β-D-glucopyranosyl-(1→6)-O-β-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 α (ERα) and β (ERβ) and the ERα 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 (T3HN) was found to play a principal role in the binding affinity of these compounds to ER.