Ichthyotoxic Phloroglucinol Derivatives from Dryopteris fragrans and Their Anti-tumor Promoting Activity

• Published in: Chemical & pharmaceutical bulletin Vol. 48; no. 8; pp. 1190 - 1195
• Main Authors: ITO, Hideyuki, MURANAKA, Takashi, MORI, Kazuko, JIN, Zhe-Xiong, TOKUDA, Harukuni, NISHINO, Hoyoku, YOSHIDA, Takashi
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.08.2000; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; anti-tumor promoter; Anticarcinogenic Agents - pharmacology; Aspidiaceae; Biological and medical sciences; Cell Line; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Cyclohexanones - pharmacology; Cyclohexanones - toxicity; dryofragin; Dryopteris fragrans; Female; General pharmacology; Herpesvirus 4, Human - drug effects; Humans; ichthyotoxic activity; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Mice, Inbred ICR; Oryzias; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phloroglucinol - analogs & derivatives; Phloroglucinol - pharmacology; Phloroglucinol - toxicity; phloroglucinol derivative; Physical Sciences; Plants - chemistry; Science & Technology; Asia; China; phloroglucinol derivative; PISCICIDAL COMPONENTS; PTERIDOPHYTA; dryofragin; PLANTS; Aspidiaceae; anti-tumor promoter; EXTRACTS; Dryopteris fragrans; ichthyotoxic activity; Epstein Barr virus; Anticarcinogen; Antitumor promotor; Medicinal plant; Polyphenol; Folk medicine; Sesquiterpenes; Piscicide; Filicineae; Gammaherpesvirinae; Terpenoid; Pharmacognosy; Whole plant; Herpesviridae; Early antigen; Rodentia; Pteridophyta; In vitro; Biological activity; Virus; In vivo; Vertebrata; Mammalia; Ketophenols; Mouse; Animal; Plant origin; Benzenic compound; Isolation; Papilloma; Structural analysis
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.48.1190

Two new ichthyotoxic compounds, aspidin PB (8) and dryofragin (9), along with three known phloroglucinol derivatives (1-3) and five terpenoids, were isolated from the whole herbs of Dryopteris fragrans by toxicity-directed fractionation using Oryzias latipes (Japanese name; medaka). The structures of the new compounds were determined by spectroscopic methods including 2D NMR techniques. Amongst the isolates, aspidin PB (8), dry-ofragin (9), and 1-5 exhibited potent ichthyotoxic activity against medaka with a median tolerance limit (TLm after 24 h) of 1.2-4.3 μg/ml. These compounds which are toxic to fish also had a potent inhibitory effect on the activation of Epstein-Barr virus early-antigen (EBV-EA) induced by tetradecanoyl phorbol 13-acetate, which is an in vitro short-term assay for anti-tumor promoting agents. Aspidin BB (2) and albicanol (4), which exhibited strong inhibitory effects on the EBV-EA activation, significantly suppressed an in vivo two-stage carcinogenesis on mouse skin.