Preparation, characterization and in vivo evaluation of novel hyaluronan containing niosomes tailored by Box-Behnken design to co-encapsulate curcumin and quercetin.

Designing novel drug delivery systems to improve drug efficiencies have gained great interests in recent years. In this study, a new vesicular system has been prepared using thin film hydration method with slight modifications, hydrophobic drugs have been used in both lipophilic and hydrophilic phases and dry film was hydrated by hyaluronan polymeric solution, to overcome curcumin and quercetin formulation drawbacks. Briefly, different formulations were prepared according to Box-Behnken design to assess the effect of HLB value, cholesterol and hyaluronan contents on the properties of niosomes. Then, the best formulation was selected for further studies and compared with conventional niosomes. The results showed that both niosomes had spherical shapes according to Transmission Electron and Atomic Force Microscopic images. Results also showed that hyaluronan containing niosomes had smaller size and higher values of zeta potential and entrapment than conventional niosomes. The average size of hyaluronan containing niosomes was 260.37 ±â€¯6.58 nm, the zeta potential was -34.97 ±â€¯1.50 mv and the entrapment for curcumin and quercetin were 98.85 ±â€¯0.55% and 93.13 ±â€¯1.22%, respectively. The release kinetic of quercetin was best fitted to Peppas model for both conventional niosome and hyaluronan containing niosomes; while, the release kinetic of curcumin was best fitted with non-conventional order 2 and three second roots of mass for hyaluronan containing niosomes and conventional niosomes, respectively. Hyaluronan containing niosomes showed higher antioxidant and anti-inflammatory effects in comparison with conventional niosomes.

Synthesis and biological evaluation of quercetin and resveratrol peptidyl derivatives as potential anticancer and antioxidant agents.

Quercetin and resveratrol are polyphenolic compounds, members of the flavonoid and the stilbene family, respectively, both medicinally important as dietary anticancer and antioxidant agents. They are present in a variety of foods-including fruits, vegetables, tea, wine, as well as other dietary supplements-and are responsible for various health benefits. Different quercetin and resveratrol esters of Leu/Met-enkephalin and tetrapeptide Leu-Ser-Lys-Leu (LSKL) were synthesized as model systems for monitoring the influence of the peptides on biological activity of resveratrol and quercetin. General formula of the main peptidyl-quercetin derivatives is 2-[3-(aa)n-4-hydroxyphenyl]-3,5,7-tri-hydroxy-4H-1-benzopyran-4-on, and the general formula of the main peptidyl-resveratrol derivatives is (E)-5-[4-(aa)n)styryl]benzene-1,3-diol. The antioxidant and anticancer activities of prepared compounds were investigated. Significant anticancer activity was obtained for the LSKL-based both quercetin and resveratrol derivatives. All prepared compounds exhibit antioxidant activity, in particular quercetin derivative containing Met-enkephalin.

The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells.

Quercetin is a major component of the plant Glycyrrhiza uralensis, which is largely used as a traditional medicine in Asia. Quercetin has been reported to have several biological activities, which include anti-viral and anti-inflammatory effects. We explored the molecular mechanism linking anti-viral and anti-inflammatory activities using an in vitro herpes simplex virus-1 (HSV-1) infection model. Raw 264.7 cells were infected with HSV-1 in the presence or absence of different concentrations of quercetin and infected cell lysates were harvested 24 h later. HSV plaque reduction assays, western blotting (HSV-1gD, HSV-1 ICP0, TLR-2, 3, 9, NF-κB, IRF3), and real time PCR (HSV-1ICP0, HSV-1UL13, HSV-1UL52) were performed to elucidate the mechanism responsible for the anti-HSV-1 effect of quercetin. In addition, TNF-α level was measured. Quercetin significantly lowered HSV infectivity in Raw 264.7 cells and inhibited the expressions of HSV proteins (gD, ICP0) and genes (ICP0, UL13, UL52). Interestingly, quercetin specifically suppressed the expression of TLR-3, and this led to the inhibitions of inflammatory transcriptional factors (NF-κB and IRF3). These findings suggest that the anti-HSV-1 effects of quercetin are related to the suppression of TLR-3 dependent inflammatory responses in Raw 264.7 cells.

Synthesis and Antiviral Activity of Quercetin Brominated Derivatives.

Reaction of quercetin (QR) (1) with bromine under various conditions was studied. Interaction of QR with 2-3 equiv. of bromine in glacial acetic acid at 35-40°C for 2-4 h and 20-22°C for 24 h led to the formation of QR 6,8-dibromide (2) (52-54% yields, 96-98% purity by HPLC). Interaction of QR with 2-5 equiv. bromine in absolute ethanol at 0-5°C and 20-22°C for 24 h led to the formation of 3-O-ethyl-QR-2,3,6,8,5'-pentabromide (3) (95-97% purity by HPLC) the output of which depends on the quantity of bromine. It was shown in MDCK cell culture that compound 2 exhibits a moderate inhibitory activity against pandemic influenza virus A/H1N1/pdm09 (EC50 6.0 µg/mL, CTD50 97.7 µg/mL, SI 16). Compound 3 was inactive.