New biological properties of pyrroloquinoline quinone and its related compounds: inhibition of chemiluminescence, lipid peroxidation and rat paw edema.
Pyrroloquinoline quinone (PQQ) inhibited the chemiluminescence (CL) from mouse peritoneal cells initiated by zymosan, carrageenin and N-formyl-methionyl-leucyl-phenylalanine and CL generated by the xanthine-xanthine oxidase reaction and the lipid peroxidation in the rat brain homogenate. The inhibitory activity of PQQ was more potent than that of idebenone, alpha-tocopherol and ascorbic acid in all the three assay systems. In the xanthine-xanthine oxidase reaction, PQQ had no effect on the formation of uric acid at the concentration of CL inhibition. These results suggest that PQQ might have a radical scavenger-like activity. Structure-activity relationship of PQQ and its six related compounds showed that the 7- and 9-carboxyl groups of PQQ as well as the orthoquinone structure are responsible for the radical scavenger-like activity. In addition, the -NH group in the pyrrole ring of PQQ seemed to be essential for the antilipid peroxidative activity in the rat brain homogenate. When administered i.p., PQQ inhibited the development of 0.1% carrageenin-induced paw edema in rats. These results suggest that PQQ might have therapeutic effects on various diseases, of which development or exacerbation has been known to be associated with radical oxygens.
Hamagishi
Y
Y
Tokyo Research Center, Bristol-Myers Research Institute, Ltd., Japan.
Murata
S
S
Kamei
H
H
Oki
T
T
Adachi
O
O
Ameyama
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D002351:Carrageenan / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D045542:PQQ Cofactor; D010529:Peritoneal Cavity / Q000166:cytology / Q000502:physiology; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D015363:Quinolones; D014970:Xanthines; D019820:Xanthine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D045542:PQQ Cofactor; D002351:Carrageenan; D015054:Zymosan; D014969:Xanthine Oxidase