β-glucuronidase inhibitors isolated from the fruit of Forsythia suspensa (Thunb.) Vahl

A methanol extract from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae), which is used as the crude drug Forsythiae Fructus ( Forsythia Fruit ; “ Rengyo ” in Japanese) and is listed in the Japanese Pharmacopoeia XIX, exerted enzymatic β-glucuronidase inhibitory activity. From the extract, we isolated a new diterpene rengyonoic acid ( 1 ) along with 19 known compounds including two diterpene ( 2 and 3 ), three triterpenes ( 4 – 6 ), seven lignans ( 7 – 13 ), two flavonoids ( 14 and 15 ), four phenylethanoids ( 16 – 19 ), and an aromatic compound ( 20 ). The structure of the new compound ( 1 ), including its absolute stereochemistry, was determined based on chemical and physicochemical evidence derived from NMR and MS spectrometry analysis as well as by comparing experimental and predicted ECD data. Among the isolates, 1 (IC 50 = 117 μM), pinoresinol ( 7 , 27.9 μM), forsythiaside A ( 16 , 18.6 μM), and suspensaside A ( 19 , 31.1 μM) exhibited β-glucuronidase inhibitory activity equivalent to that of a positive compound, d -saccharic 1,4-lactone (38.6 μM).