The flavonoid luteolin inhibits niacin-induced flush.
OBJECTIVE
Sustained release niacin effectively lowers serum cholesterol, LDL and triglycerides, while raising HDL. However, 75% of patients experience cutaneous warmth and itching known as flush, leading to discontinuation. Acetylsalicylic acid (aspirin) reduces this flush only by about 30%, presumably through decreasing prostaglandin D2 (PGD2). We investigated whether niacin-induced flush in a rat model involves PGD2 and 5-HT, and the effect of certain flavonoids.


METHODS
Three skin temperature measurements from each ear were recorded with an infrared pyrometer for each time point immediately before i.p. injection with either niacin or a flavonoid. The temperature was then measured every 10 min for 60 min.


RESULTS
Niacin (7.5 mg per rat, equivalent to a human dose of 1750 mg per 80 kg) maximally increased ear temperature to 1.9+/-0.2 degrees C at 45 min. Quercetin and luteolin (4.3 mg per rat; 1000 mg per human), administered i.p. 45 min prior to niacin, inhibited the niacin effect by 96 and 88%, respectively. Aspirin (1.22 mg per rat; 325 mg per human) inhibited the niacin effect by only 30%. Niacin almost doubled plasma PGD2 and 5-HT, but aspirin reduced only PGD2 by 86%. In contrast, luteolin inhibited both plasma PGD2 and 5-HT levels by 100 and 67%, respectively. CONCLUSIONS AND IMPLICATIONS. Niacin-induced skin temperature increase is associated with PGD2 and 5-HT elevations in rats; luteolin may be a better inhibitor of niacin-induced flush because it blocks the rise in both mediators.
Papaliodis
D
D
Laboratory for Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA, USA.
Boucher
W
W
Kempuraj
D
D
Theoharides
T C
TC
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D005483:Flushing / Q000139:chemically induced* / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000009:adverse effects*; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D009525:Niacin / Q000009:adverse effects*; D015230:Prostaglandin D2 / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D000960:Hypolipidemic Agents; D009525:Niacin; D012701:Serotonin; D011794:Quercetin; D047311:Luteolin; D001241:Aspirin; D015230:Prostaglandin D2