rvH1N1 Neuraminidase Inhibitory Activities of Phenolics from Perilla frutescens (L.) and Their Contents in Cultivars and Germplasm

The influenza neuraminidase (NA, E.C. 3.2.1.18), an antiviral, has been the target of high pharmaceutical companies due to its essential role in viral replication cycle. Perilla frutescens (P. frutescens) is used in traditional Chinese medicine for various diseases, such as cold due to wind-cold, headache and cough. In this context, four major polyphenolic compounds including rosmarinic acid-3-O-glucoside (1), rosmarinic acid (2), luteolin (3), and apigenin (4) isolated from P. frutescens were evaluated for their inhibitory effect on recombinant virus H1N1 neuraminidase (rvH1N1 NA). Among the test compounds, rosmarinic acid and luteolin inhibited the rvH1N1 NA with an IC50 of 46.7 and 8.4 &#120583;M, respectively. The inhibition kinetics analyzed by the Dixon plots indicated that rosmarinic acid and luteolin were noncompetitive inhibitors and that the inhibition constant, KI, was established as 43.9 and 14.3 &#61549;M, respectively. In addition, 578 genetically diverse accessions and 39 cultivars of P. frutescens were analyzed using HPLC to characterize the diversity of polyphenolic composition and concentration. The individual and total compositions exhibited significant difference (P < 0.05), especially rosmarinic acid which was detected as the predominant metabolite in all accessions (58.8%) and cultivars (62.8%). Yeupsil and Sangback cultivars exhibited the highest rosmarinic acid (3,393.5 &#120583;g/g) and luteolin (383.3 &#120583;g/g) content respectively. YCPL177-2 with the high concentration (889.8 &#120583;g/g) of luteolin may be used as a genetic resource for breeding elite cultivars.