Antifilarial activity in vitro and in vivo of some flavonoids tested against Brugia malayi.
We evaluated the antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 μg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 μg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 μg/ml. Flavone immobilized female adult worms at 31.2 μg/ml (MTT>80%) and microfilariae at 62.5 μg/ml. Rutin killed microfilariae at 125 μg/ml and inhibited MTT-reduction in female worms for >65% at 500 μg/ml. Naringin had adulticidal effects at 125 μg/ml while chrysin killed microfilariae at 250 μg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new antifilarial agent(s). This is the first report on antifilarial efficacy of flavonoids.
Lakshmi
V
V
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India.
Joseph
S K
SK
Srivastava
S
S
Verma
S K
SK
Sahoo
M K
MK
Dube
V
V
Mishra
S K
SK
Murthy
P K
PK
D000818:Animals; D017178:Brugia malayi / Q000187:drug effects* / Q000302:isolation & purification; D004396:Coloring Agents; D004195:Disease Models, Animal; D004605:Elephantiasis, Filarial / Q000188:drug therapy; D005260:Female; D005369:Filaricides / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology* / Q000592:standards; D005419:Flavonoids / Q000494:pharmacology* / Q000592:standards; D005849:Gerbillinae / Q000469:parasitology; D006569:Hesperidin / Q000494:pharmacology; D006801:Humans; D008297:Male; D051189:Murinae / Q000469:parasitology; D012431:Rutin / Q000494:pharmacology; D016019:Survival Analysis; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D005369:Filaricides; D044950:Flavanones; D005419:Flavonoids; D013778:Tetrazolium Salts; D013844:Thiazoles; C043561:chrysin; D012431:Rutin; D006569:Hesperidin; C022616:thiazolyl blue; C005273:naringenin; C013015:hesperetin