Computational analysis and in vitro investigation on Citrus flavonoids for inflammatory, diabetic and AGEs targets

Abstract Flavonoids are a diverse class of polyphenolic substances largely found in plants including citrus peels and are reported to posess a variety of biological activities. We investigated important flavonoids apigenin, hesperidin, narigin, quercetin and tangeritine against diabetes and associated conditions. In current project drug likeness, ADMET analysis, molecular docking and in vitro assays were performed. The apigenin, quercetin and tanagretin exhibited compliance with Lipinski's rule of five. The molecular docking analysis showed best fit in transcriptional regulator 3TOP and 1IK3 in all tested compounds. During antioxidant assays, all flavonoids presented excellent activities. In the α-glucosidase assay, quercetin showed highest inhibition (76% at final concentration of 52 µg/ml) followed by tangeritin (73% at final concentration of 52 µg/ml). In case of 15-Lox assay, highest inhibition was seen in case of quercetin (75%) followed by apigenin (53%). In the AGEs assay, the quercetin showed 47% inhbition of protein cross link formation preceeded by the tenegretin exhited 37% inhibition. It was therefore concluded that tested flavonoids have significant activities in both in silico and in vitro models that is mainly due to differences in structural features and polar surface area.

Anti-infective, cytotoxic and antioxidant activity of Ziziphus oxyphylla and Cedrela serrata

Objective: To search for the most active antimicrobial and antioxidant sub-fractions related to traditional use of Ziziphus oxyphylla (Z. oxyphylla) and Cedrela serrata (C. serrata) in Pakistan against infectious and liver diseases. Methods: Factions of different polarity were tested in vitro for their antiprotozoal, antimalarial, antibacterial and antifungal activity against different pathogens. Cytotoxicity on MRC-5 cell lines (human lung fibroblasts) as well as, in vitro radical scavenging activity was evaluated using the 1, 1-diphenyl-2-picrylhydrazyl radical assay. Results: The highest antiprotozoal activity was observed for the CHCl3 fractions of Z. oxyphylla roots and leaves, and C. serrata bark. The CHCl3 and EtOAc fractions of Z. oxyphylla roots, the CHCl3 fraction of Z. oxyphylla leaves, the EtOAc and the residual MeOH: H2O fraction of C. serrata bark showed antibacterial activity against Staphylo-coccus aureus. The same residual MeOH: H2O fraction of C. serrata bark was active against Candida albicans. The highest antioxidant activity was observed for the more hydrophilic EtOAc fractions of Z. oxyphylla leaves, C. serrata bark and leaves, and the residual MeOH:H2O fraction of C. serrata bark. Conclusions: This study supports at least in part the traditional uses of these plants for antimicrobial purposes and against liver diseases.

Antioxidant, Antliglycation and Antimicrobial Activities of Ziziphus oxyphylla and Cedrela serrata Extracts.

Aims: To determine the antioxidant, antiglycation and antibacterial activity of two selected plants found wild in Pakistan (Ziziphus oxyphylla and Cedrela serrata). Study Design: In vitro assessment of antioxidant assays, phenolic and flavonoid content, protein-glycation inhibition and antibacterial study. Place and Duration of Study: Department of Pharmaceutical Sciences, University of Antwerp Belgium (February - April 2013; Antioxidant, Protein glycation). Department of Pharmacognosy, University of Karachi, Pakistan (March – June, 2012; antibacterial). Methodology: In vitro laboratory experimental tests; preparation of plant extracts, antioxidant assays (ABTS.+, PMS-NADH radicals), total phenol, total flavonoid; protein glycation (fluorescence); susceptibility tests (zones of inhibition). Results: The bark of C. serrata contained the highest amount of total phenol (0.35 ± 0.04 mg GAE/g extract) and exhibited significantly superior ABTS.+ and PMS superoxide radical scavenging activity with IC50 values of 0.043 ± 0.001 mg/ml and 0.18 ± 0.01 mg/ml, respectively (P=0.05). Similarly, the protein-glycation assay revealed that the bark of C. serrata had the best inhibitory property with a low IC50 value of 0.61 ± 0.02 mg/ml (P=0.05), probably due to the presence of high amounts of total phenol. Furthermore, the various extracts showed considerable inhibition against both Gram–positive and – negative bacterial growth when compared against two standard drugs neomycin and doxycycline. Conclusion: The results of this study substantiate a probable role for these plants to be utilized as a natural source of antioxidant having a wide range of bioactivities.