Papyriflavonol A from Broussonetia papyrifera Inhibits the Passive Cutaneous Anaphylaxis Reaction and Has a Secretory Phospholipase A2-Inhibitory Activity.

Abstract

Papyriflavonol A, a new prenylated flavonol isolated from Broussonetia papyrifera, selectively inhibits recombinant human secretory phospholipase A 2 s (sPLA 2 s). Papyriflavonol A was found to inhibit human group IIA and V sPLA 2 s potently and irreversibly in a dose-dependent manner, with respective IC 50 values of 3.9 and 4.5 m mM. The inhibitory effects of papyriflavonol A against bovine group IB (IC 50 of 76.9 m mM) and the human group X (IC 50 of 225 m mM) sPLA 2 s were weaker than those against human group IIA and V sPLA 2 s, and human group IIF sPLA 2 was not inhibited. In addition, papyriflavonol A potently inhibited the stimulus-induced production of leukotriene C 4 with an IC 50 value of approximately 0.64 m mM in mouse bone marrow-derived mast cells. In addition, papyriflavonol A significantly reduced IgE-dependent passive cutaneous anaphylaxis in rats. These results indicate that papyriflavonol A provides a basis for novel types of antiinflammatory drugs.

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

“…Since many (potent) flavonoids have been analyzed for inhibition of 5-LO product synthesis only in intact cells, it is not always clear if reduced formation of 5-LO products is caused by direct inhibition of 5-LO or by inhibition of PLA 2 enzymes (reduced AA supply). In fact, certain biflavonoids like ginkgetin 25 [101] and ochnaflavone 24 [102] or papyriflavonol 20 [103] and quercetin 11 [104] that all suppress 5-LO product synthesis, efficiently inhibit PLA 2 enzymes.…”

“…Of interest, the prenylated flavonoids including payriflavonol 20, morusin 21, artonin E 22, sanggenon D 26, sophoraflavanone G 30 and kenusanone A 31 are highly efficient direct 5-LO inhibitors with IC 50 values 0.09 to 7 mM in cellfree assays [105]. Unfortunately, among those, only for papyriflavonol 20 has the efficacy in intact cells been demonstrated [103]. Although for inhibition of cellular 5-LO, the flavonoid aglycones are generally superior over the corresponding glycosides, the myricetin 3-O-b-D-glucuronide 13 is more efficient than the corresponding aglycone myricetin 12 under comparable assay conditions [99], [109], probably related to more effective cellular uptake of the glycoside by specific transporters.…”

“…Although for inhibition of cellular 5-LO, the flavonoid aglycones are generally superior over the corresponding glycosides, the myricetin 3-O-b-D-glucuronide 13 is more efficient than the corresponding aglycone myricetin 12 under comparable assay conditions [99], [109], probably related to more effective cellular uptake of the glycoside by specific transporters. Since conventional flavonoids show only weak efficacy after oral administration, presumably due to poor bioavailability (low absorption) and/or rapid metabolism and elimination, the more lipophilic prenylated derivatives may possess the advantage of facilitated membrane (and skin) penetration in addition to their higher potency as 5-LO inhibitors, suggesting a potential for topical treatment of inflammatory skin diseases [103], [105], [113]. Nevertheless, oral intake of flavonoid-rich nutrition (i. e., chocolate) led to significant decreases in the plasma concentrations of cys-LTs in human subjects [114] supporting the beneficial effects of daily dietary intake of flavonoids.…”

Anti-inflammatory and opioid-like activities in methanol extract of Mikania lindleyana, sucuriju

“…The fact that naloxone reverse totally the first and partially the second Anti-inflammatory and opioid-like activities in methanol extract of Mikania lindleyana, sucuriju Frederico A. Vanderlinde et al and anti-inflammatory (Middleton et al, 2000), besides the blockade of phospholipase A 2 , inhibit the cyclooxygenase and/or the lipoxygenase pathways of arachidonate metabolism (Lindahl & Tagesson, 1997;Middleton et al, 2000;Kwak et al, 2003). Although the phytochemical study of hexane and dichloromethane extracts has detected stigmasterol compound (Guilhon et al, 1998a(Guilhon et al, ,b,c, 1999, high doses of these extractions were ineffective in acetic acid-induced writhing model, however the antinociceptive and anti-inflammatory activities of ME can be attributed to flavonoids compounds, such quercetin and rutin, present in this extraction (Moreira et al, 2008), without excluding the possibility of stigmasterol, and other chemical compounds present in the aerial parts of plant also participate in the analgesic and anti-inflammatory effectiveness of specie.…”

Inhibition of Experimental Lung Inflammation and Bronchitis by Phytoformula Containing Broussonetia papyrifera and Lonicera japonica

“…Among these, papyrifl avonol A is a relatively specifi c 5-LOX inhibitor (Chi et al, 2001b). Papyrifl avonol A has also been found to inhibit allergic responses in vivo (Kwak et al, 2003). Because 5-LOX inhibitors have the potential to treat bronchial asthma as well as bronchitis, BL is thought to inhibit lung infl ammation.…”