Distinctive Antioxidant and Antiinflammatory Effects of Flavonols

Abstract

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.

Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

“…The same dose of fisetin also reduced LPS-induced increases in extracellular PGE2 levels as well as increases in the expression of the COX2, iNOS and interleukin-1b genes. Similar to the results obtained with other types of cells treated with fisetin and LPS [85,92], the effects of fisetin on microglial activation appeared to be mediated by inhibition of LPS-stimulated NF-jB activation. Similar data were obtained with primary microglial cells isolated from the cerebral cortices of 1 day old mice.…”

Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

“…Four compounds (genistein, kaempferol, quercetin, and daidzein) inhibited the activation of two important gene transcription factors for iNOS, i.e., signal transducer and activator of transcription 1 (STAT-1) and NF-kB, whereas four other compounds (flavone, isorhamnetin, naringenin, and pelargonidin) only inhibited NF-kB (Hämälänein et al, 2007). Another study showed that selected flavonoids, including fisetin, kaempferol, morin, myricetin, and quercetin, exhibited distinct antioxidant properties against different types of free radicals (Wang et al, 2006). These results indicate that flavonoids have different antioxidant and anti-inflammatory effects despite their structural similarity (Hämälänein et al, 2007;Wang et al, 2006).…”

“…Another study showed that selected flavonoids, including fisetin, kaempferol, morin, myricetin, and quercetin, exhibited distinct antioxidant properties against different types of free radicals (Wang et al, 2006). These results indicate that flavonoids have different antioxidant and anti-inflammatory effects despite their structural similarity (Hämälänein et al, 2007;Wang et al, 2006). Some flavonoids stimulate macrophages stop further production of eicosanoids and destroy excess oxidants (Havsteen, 2002).…”

A sensitive microextraction by packed sorbent-based methodology combined with ultra-high pressure liquid chromatography as a powerful technique for analysis of biologically active flavonols in wines

“…Flavonoids have long been recognized to exhibit antiinflammatory, antioxidant, anti-allergic, hepatoprotective, antithrombotic, anti-viral, anti-carcinogenic activities and immune modulating functions, among others [8][9][10][11]. The flavonoids also act as potent metal chelators and free radical scavengers and are powerful chain-breaking antioxidants [12], and control protein oxidation and advanced glycation end products (AGEs) formation [13].…”

“…The position and the degree of hydroxylation have been demonstrated to be the most important for their biochemical and pharmacological actions [25,26]. Wang et al [11] examined the antioxidant and antiinflammatory activities of selected flavonols, including kaempferol, quercetin and myricetin. Their results showed that flavonols exhibit distinctive antioxidant and anti-inflammatory potentials and that the structures, required to strengthen these activities, vary with sorts of free radicals and mechanisms.…”