Evaluation of the anti-inflammatory profile of quercetin and enhancement of its effects with b- cyclodextrin

Abstract EN

Quercetin (QUR) is a natural non-toxic flavone with several pharmacological effects.

Its anti-inflammatory activity was evaluated using different inflammatory models.

Inflammation was induced by injecting carrageenan, dextrean, platelet-activating factor (PAF) as well as kaolin into the right hind paw of rats.

In addition, the effect of OUR and its inclusion complexes with ?-cyclodextrin (?CD) on the rate of accelerated capillary permeability elicited by histamine was investigated.

Piroxicam and indomethacin were used as reference drugs.

QUR (30 mg/kg, P.O.

demonstrated a significant anti-inflammatory activity against all the tested inflammatory models.

In contrast to piroxicam (10 mg/kg, P.O.) and QUR (30 mg/kg, P.O.), indomethacin (10 mg/kg, P.O.) was ineffective against dextran-induced paw edema.

On edema induced by PAF, only QUR (30 mg/kg, P.O.) and piroxicam (10/kg, P.O.) significantly inhibited the inflammatory process.

Both dextran- and PAF-induced edemas are thought to be unrelated to prostaglandins in the rat system.

The mode of action of QUR is thought to be not through cycloxygenase inhibition.

QUR (30 mg/kg, P.O.) inhibited the early and late stages of kaolin-induced edema, while piroxicam (10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) only inhibited the late stage.

The results of this study confirmed the potent anti-inflammatory activity of QUR and at the same time indicated that its mechanism of action is different from that of other anti-inflammatory agents.

Inclusion complexation of QUR with ?CD was tried for resolving problems resulting from its water insolubility and low bioavaiability.

An equilibrium phase solubility diagram was obtained for the QUR- ?CD system in water.

The solubility of QUR increased on addition of ?CD, displaying an Ap type phase diagram.

The stability constant (Kc) was calculated from the slope of the initial straight portion of the curve and was found to be 236 M-1.

The stability constant was also obtained from UV spectra to be 237 M-1 which showed a good agreement with the value of Kc obtained by the solubility method.

The formation of the complex in the solid state was confirmed by infrared spectroscopy (IR).

The amount of QUR dissolved from inclusion complexes 1:1 (CI) and 1:2 (CII) in water are more 15 and 25 times, respectively than the equal amount of free QUR.

Complexation of QUR with ?CD was found to increase water solubility, bioavailability as well as anti-inflammatory activity of the drug from its oral administration.