The pervasiveness of oral bacterial infections in diabetic patients is a serious health concern that may produce severe complications. We investigated 26 Ayurvedic medicinal plants traditionally used for treatment of the oral bacterial infections with the aim to look for new promising drug leads that can be further employed for herbal formulation design. The plants were grouped into three categories based on traditional usage. All plant extracts were examined for antibacterial, antibiofilm and antiquorum-sensing properties. The plants with significant activities including Juglans regia, Syzygium aromaticum, Eruca sativa, Myristica fragrans, Punica granatum and Azadirachta indica were further analyzed using HPLC-DAD-QToF and GC-MS. In silico and in vitro activity was evaluated for selected constituents. Finally, it could be concluded that eugenol and 2-phenylethylisothiocyanate are major contributors towards inhibition of bacterial biofilms and quorum sensing.
Diabetes mellitus (DM) has a worldwide prevalence with very alarming situation in low-income and developing countries including Pakistan. During this project, we investigated peels of two commonly used Citrus species, i.e., C. sinensis and hybrid Citrus (C. nobilis and C. delicense) for their antioxidant, antidiabetic, antiglycation, antimicrobial and anti-inflammatory activities. Initially the peels were dried and extracted with various solvents. Then, HPLC and ATR-FTIR analysis was performed and finally the extracts and fractions were analyzed for their biological properties. The HPLC and ATR-FTIR data showed the presence of phenolics and flavonoids. In C. sinensis peels, high concentration of phenolics (87.3 ± 0.11 mg/g GAE) were observed in ethyl acetate part followed by methanolic fraction (72.5 ± 0.12 mg/gGAE). Both extracts exhibited strong antioxidant activity, antimicrobial and anti-biofilm properties. In Advanced Glycation End Products (AGEs) assay, total extract of C. sinensis showed moderate (IC 50 = 1.23 mg/mL) activity. All tested fractions were active in respect of a-glucosidase inhibition, whereas in 15-lox assay, only n-hexane fraction presented excellent activity (90%). On the other hand, in case of hybrid Citrus, a moderate inhibition was found in the case of total extract (IC 50 = 0.25 mg/mL). Among fractions, highest inhibition was noticed for the methanolic part of crude extract (IC 50 = 0.10 mg/mL). Both the total crude extract (IC 50 = 0.23 mg/ml) and methanolic part of plant extract (IC 50 =0.36 mg/ml) showed a-glucosidase inhibition, whereas only moderate 15-lox inhibition was observed.
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.
Ferula narthex Boiss. is commonly used in Pakistan and India as spice and it is associated with diverse biological activities including antidiabetic and anti-inflammatory. Research has suggested that the genus Ferula is rich in sesquiterpene coumarins. During this project, both in vitro and in silico models were adopted to investigate its traditional use. Based on structural diversity, selected compounds isolated from the exudate were processed for molecular docking studies. The negative binding energies and close proximity to residues in the binding pocket of selected targets including human α-glucosidase (PDB ID 3TOP) and soybean LOX (PDB ID 1IK3) were recorded, which indicated high affinity and tight binding capacity of 10'-R-acetyl-karatavacinol and 10'-R-karatavacinol towards the active sites of αglucosidase and 15-lipoxygenase (15-LOX). 10'-R-acetyl karatavacinol exhibited the highest inhibition of α-glucosidase in vitro (IC50 0.05mM), whereas in the 15-LOX inhibition assay, 10'-R-karatavacinol was most active (70%, at 0.023 mM final concentration). It was therefore concluded that 10'-R-acetyl-karatavacinol had the highest α-glucosidase inhibitory activity, whereas 10'-R-karatavacinol was a 15-LOX inhibitor with potentially antiinflammatory properties.
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