Evaluation of the anti-inflammatory profile of quercetin enhancing its effects by beta-cyclodextrin

ABSTRACT

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, dextran, platelet-activating factor [PAF] as well as kaolin into the right hind paw of rat. In addition, the effect of QUR and its inclusion complexes with beta -cyclodextrin [beta-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 significant anti-inflammatory activity against all the tested inflammatory models. In contrast to piroxicam [10 mg/kg, p.o.] and QWR [30 mg/kg, p.o.], indomethacin [10-30 mg/kg] was ineffective against PAF-and dextraninduced paw edemas. Both dextran- and PAF-induced edemas are thought to be unrelated to prostaglandins in the rat system. The mode of action of QUR is, therefore, considered to be not through cyclooxygenase inhibition. QUR [30 mg/kg, p.o.] inhibited the early stage of kaolin-induced edema, while piroxicam [10 mg/kg, p.o.] and indomethacin [10 mg/kg] inhibited the late one. The results of the study confirmed the anti-inflammatory activity of QUR and at the same time indicated that its mechanism of action is at least different from that of NSAIDs. Iclusion complexation of quercetin with beta-CD was tried for resolving problems resulting from its water insolubility and low bioavailability after oral administration. An equilibrium phase solubility diagram was obtained for the QUR- beta -CD system in water. The solubility of QUR increased on addition of beta -CD, displaying an A type phase diagram, which indicates that the soluble complexes contained more than one molecule of ligand at higher beta-CD concentration. Stability constant [Kc] was calculated from the slope of initial straight portion of the curve and found to be 236 M-1. The stability constant was also obtained from UV spectra to be 237M-1 which showed a good agreement with the value of Kc obtained by the solubility method. Complexation of QUR with beta -CD was found to increase water solubility, anti-inflammatory activity and in turn the bioavailability of the drug after its oral administration