Olean-27-carboxylic Acid-Type Triterpenes with Potent Antibacterial Activity from Aceriphyllum rossii

Aceriphyllum rossii Engler (Saxifragaceae) have been used as a nutritious food in Korea. We found that the methanol extract of the root portion of A. rossii potently inhibited the growth of Staphylococcus aureus, with a minimal inhibitory concentration (MIC) value of 8 mu g/mL. Using mass spectrometry and nuclear magnetic resonance (NMR) studies, four active constituents were isolated and identified: aceriphyllic acid A, 3-oxoolean-12-en-27-oic acid, 3 alpha-hydroxyolean-12-en-27-oic acid, and 3 beta-hydroxyolean-12-en-27-oic acid. Aceriphyllic acid A and 3-oxoolean-12-en-27-oic acid showed a potent antibacterial activity against several strains of S. aureus, including methicillin-resistant S. aureus and quinolone-resistant S. aureus, with MIC values of 2-8 mu g/mL, while 3 alpha-hydroxyolean-12-en-27-oic acid and 3 beta-hydroxyolean-12-en-27-oic acid exhibited a very weak activity, with MIC values of 128 mu g/mL. The methyl ester derivative of aceriphyllic acid A lost its antibacterial activity. The time-kill study against S. aureus indicated that aceriphyllic acid A had rapid bactericidal activity. These results indicated that aceriphyllic acid A and 3-oxoolean-12-en-27-oic acid are the most active principles, and both the carboxylic group at C-27 and the hydroxyl group at C-24 in aceriphyllic acid A are critical for the rapid bactericidal activity.