ABSTRACT
Chemical investigation on polyphenol-rich fractions of Cowania mexicana and Coleogyne ramosissima (Rosaceae) which showed significant inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), has led to the characterization of 10 compounds including C-glucosidic ellagitannin monomers and dimers from the former plant, and 17 polyphenols including flavonoid glycosides from the latter. The effects of individual components and their analogues with related structures on the TPA-induced EBV-EA activation were then evaluated. Among the compounds isolated from C. mexicana, two C-glucosidic ellagitannins, alienanin B and stenophyllanin A and a nitrile glucoside (lithospermoside), and among the constituents from C. ramosissima, two flavonoid glycosides, isorhamnetin 3-0-beta-D-glucoside and narcissin were revealed to possess strong inhibitory effects on EVB-EA activation, the potencies of which were either comparable to or stronger than that of a green tea polyphenol, (-)-epigallocatechin gallate. These polyphenols except for nitrile glucoside, which was not tested owing to an insufficient amount, were also found to exhibit anti-tumor promoting activity in two-stage mouse skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) and TPA.
Subject(s)
Antineoplastic Agents/pharmacology , Flavonoids , Papilloma/drug therapy , Phenols/pharmacology , Polymers/pharmacology , Rosales/chemistry , Skin Neoplasms/drug therapy , Virus Activation/drug effects , 9,10-Dimethyl-1,2-benzanthracene , Animals , Antigens, Viral/drug effects , Antineoplastic Agents/isolation & purification , Drug Screening Assays, Antitumor , Herpesvirus 4, Human/drug effects , Herpesvirus 4, Human/growth & development , Humans , Mice , Mice, Inbred ICR , Papilloma/chemically induced , Phenols/isolation & purification , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plants, Medicinal , Polymers/isolation & purification , Polyphenols , Skin Neoplasms/chemically induced , Specific Pathogen-Free Organisms , Structure-Activity Relationship , Tetradecanoylphorbol Acetate , Tumor Cells, CulturedABSTRACT
In our search for possible anti-tumor-promoters, we carried out an investigation of the leaves and branches of Cowania mexicana D. DON (Rosaceae). Two new cucurbitane type triterpenes, 15-oxo-cucurbitacin F (3) and 15-oxo-23,24-dihydrocucurbitacin F (4), were isolated together with cucurbitacin F (1) and 23,24-dihydrocucurbitacin F (2). These triterpenes were inhibitorss of Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate, a well-known tumor-promoter. The structures of 3 and 4 were determined from 2D-NMR spectral data and difference NOE experiments.