Improvement of (+)-catechin inhibitory activity on human PMN respiratory burst by (+)-3-O-propionyl and (-)-3-O-valeryl substitution.
Catechins and their derivatives are abundant flavanols in the plant kingdom. Usually, catechin activity correlates with chemical structure. We hypothesized that by adding hydrophobic groups to the native catechin, we could ameliorate penetration of the cell and make the derivatives more active than native molecule in inhibiting polymorphonuclear leucocyte (PMN) oxidative burst. This study was designed to compare the antioxidant activity of native catechin with that of (+)-3-propionylcatechin and (-)-3-Ovalerylcatechin esters by two cell-free colorimetric methods and by their effects on whole blood leucocytes as well as on isolated PMN chemiluminescence activity. The results showed that the colorimetric methods did not detect differences between catechins. On the contrary, cellular chemiluminescence studies showed that light emission by resting, as well as by phorbol myristate acetate (PMA)-stimulated PMNs and whole blood leucocytes was inhibited by catechin esters more intensively than native catechin. The compartmental chemiluminescence evaluation showed that the extracellular activity was similar with all catechins, while the intracellular activity was higher with esters. PMN pre-incubation, with catechins at various times before stimulation with PMA, enhanced the inhibitory activity of all compounds. Since the esterification with propionic or valeric acid increased the lipophilicity of (+)-catechin, we hypothesized that native and esterified catechins have different intracellular availability and therefore differ in effectiveness. An ancillary result obtained is that a single approach, chemical or cellular, is not sufficient to evaluate overall antioxidant activity in biological sytems. The results indicate that modified catechins may be very intriguing as possible future leucocyte modulating drugs, with possible applications in vascular and inflammatory diseases.
Vuotto
Maria Luisa
ML
Dipartimento di Patologia Generale, Seconda Università degli Studi, Napoli, Italy. marialuisa.vuotto@unina2.it
Miranda
Rosario
R
Ritieni
Alberto
A
Basile
Adriana
A
Ricciardi
Luca
L
Di Prisco
Rocco
R
Nicolosi
Giovanni
G
Mascolo
Nicola
N
D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D052160:Benzothiazoles; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003124:Colorimetry; D004952:Esters / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008163:Luminescent Measurements; D008165:Luminol; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013451:Sulfonic Acids / Q000737:chemistry
D000975:Antioxidants; D052160:Benzothiazoles; D004952:Esters; D007202:Indicators and Reagents; D013451:Sulfonic Acids; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D008165:Luminol; D002392:Catechin