Distinctive antioxidant and antiinflammatory effects of flavonols.
The antioxidant and antiinflammatory effects of flavonols have been suggested to be structure-related. Results revealed that selected flavonols, including fisetin (F), kaempferol (K), morin (MO), myricetin (MY), and quercetin (Q), exhibited distinctive free radical scavenging properties against different kinds of free radicals. The H donation (DPPH bleaching) potential was Q > F approximately equals MY > MO > K, indicating that the presence of a 3',4'-catechol moiety in the B ring correlated with high activity. The 4'-OH in the B ring was suggested to be important for reducing xanthing/xanthine oxidase-generated superoxide; while an additional OH moiety on the ortho sites (3' or 5') attenuated the effect as the observed inhibitory potency was K approximately equals MO > Q > F > MY. The relative inhibitory effect for Fenton-mediated hydroxyl radical was K approximately equals MO approximately equals Q > F > MY. This result implies the involvement of 4-keto, 5-OH region in Fe++ chelating and the negative effect of pyrogallol moiety in the B ring. Similar to the inhibitory activity against a N-formyl-methionyl-leucyl-phenylalanine (f-MLP)-stimulated oxidative burst in human polymorphonuclear neutrophils (PMN), our result showed that the structural peculiarity of the di-OH in the B ring obviously rendered F, Q, and MO more potent as ROS inhibitors than MY and K, which have tri- and mono-OH in the B ring, respectively. All of the previous data indicated that the structure prerequisite to reinforce the free radical scavenging activity varies with the type of free radical. We further analyzed the effects of flavonols on nitric oxide (NO) production in endotoxin-stimulated murine macrophages, RAW264.7 cells. Results showed that all flavonols (up to 10 microM) inhibited NO production without exerting detectable cytotoxicity. F, K, and Q dose-dependently repressed iNOS mRNA expression and prostaglandin E2 (PGE2) production, in part through an attenuating NF-kappaB signaling pathway. This result indicates that flavonols, despite structural similarity, have different antioxidant and antiinflammatory effects.
Wang
Lisu
L
Department of Environmental and Occupational Health, Medical College, Cheng-Kung University, Tainan 701, Taiwan.
Tu
Yi-Chen
YC
Lian
Tzi-Wei
TW
Hung
Jing-Ting
JT
Yen
Jui-Hung
JH
Wu
Ming-Jiuan
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000097:blood; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005419:Flavonoids; D044948:Flavonols; D016166:Free Radical Scavengers; D044949:Kaempferols; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C006552:kaempferol; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone; C017875:fisetin