Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities.
Five flavonols (3, 5, and 9-11) were isolated from Rhodiola rosea, and compared with commercially available flavonoids (1, 2, 4, 6-8, and 12-14) to facilitate analysis of their structure-activity relationship (SAR). All compounds (1-14) showed neuraminidase inhibitory activities with IC(50) values ranging from 0.8 to 56.9 microM. The in vitro anti-influenza virus activities of flavonoids 1-6, 8-12, and 14 were evaluated using two influenza viral strains, H1N1 (A/PR/8/34) and H9N2 (A/Chicken/Korea/MS96/96), testing their ability to reduce virus-induced cytopathic effect (CPE) in MDCK cells. We found that the activity of these compounds ranged from 30.2 to 99.1 microM against H1N1- and 18.5 to 133.6 microM against H9N2-induced CPE. Of compounds 1-14, gossypetin (6) exhibited the most potent inhibitory activity, with IC(50) values of 0.8 and 2.6 microM on neuraminidases from Clostridium perfringens and recombinant influenza virus A (rvH1N1), respectively. In contrast, kaempferol (3) exhibited the highest activity against two influenza viruses, H1N1 and H9N2 with EC(50) values of 30.2 and 18.5 microM, respectively. Activity depended on the position and number of hydroxy groups on the flavonoids backbone. In kinetic studies, all isolated compounds behaved as noncompetitive inhibitors.
Jeong
Hyung Jae
HJ
Bioindustry Technology Research Center and AI Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 580-185, Republic of Korea.
Ryu
Young Bae
YB
Park
Su-Jin
SJ
Kim
Jang Hoon
JH
Kwon
Hyung-Jun
HJ
Kim
Jin Hyo
JH
Park
Ki Hun
KH
Rho
Mun-Chual
MC
Lee
Woo Song
WS
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification; D003016:Clostridium perfringens / Q000187:drug effects; D004285:Dogs; D044948:Flavonols / Q000494:pharmacology* / Q000627:therapeutic use; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D018517:Plant Roots / Q000737:chemistry; D029771:Rhodiola / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D044948:Flavonols; D009439:Neuraminidase