Regulation of wound strength by Ocimum sanctum: in silico and in vivo evidences.

Background: The present work has been an attempt to facilitate the scientific understanding of the wound strength by Ocimum sanctum (OS, holy basil) a traditional knowledge practiced since ancient times in India. Methods: The in vivo Incision (wound strength) and Dead space wound models (biochemical estimation of components of ECM) in rats and In silico method, where one of the target proteins from each class of MMPs involved in wound strength was selected for molecular docking with eugenol (one of the flavonoid present in OS). Results: Molecular docking showed that eugenol was able to inhibit all selected MMPs, i.e. collagenase (-6.37 Kcal/mol), gelatinase (-5.99 Kcal/mol), elastase (-6.31 Kcal/mol) and stromelysin (-5.79 Kcal/mol). Ethanolic extract of Ocimum sanctum (OSE, 200-800 mg/kg) when administered as suspension showed dose-dependent increase in wound breaking strength in in vivo Incision wound rat model. OSE 400 mg/kg produced a significant increase in protein and collagen constituents like hydroxyproline, hexuronic acid and hexosamine in the connective tissue content of extracellular matrix when studied in Dead space wound model in rat. Conclusions: The present study is an attempt to correlate the in vivo findings on wound strength promoting activity by Ocimum sanctum with in silico tools.

Molecular construction of NADH-cytochrome b5 reductase inhibition by flavonoids and chemical basis of difference in inhibition potential: Molecular dynamics simulation study.

NADH-cytochrome b5 reductase, a flavoprotein, plays a central role in many diverse metabolic reactions. NADH-cytochrome b5 reductase has been shown to be responsible for the generation of free radicals from heterocyclic amines. Flavonoids compounds share remarkable similarity in structure but showed differences in their cytochrome b5 reductase inhibition pattern. Our molecular dynamics simulation studies revealed that the difference in substitution at C3 position of ring C may lead to difference in interaction with enzyme. Absence of hydroxyl group substitution at C3 in luteolin facilitates the strong cation-π interaction between Lys185 and ring A, and C and π-π between Phe92 and ring A, and C along with h-bonding between Lys185 and oxo group. Ring B of luteolin showed strong π-π interaction with FAD. These interactions were found absent in quercetin and taxifolin. These results suggest that absence of hydroxyl group substitution at C3 increases the potency of flavonoid inhibitors for cytochrome b5 reductase.

Taxifolin acts as type I inhibitor for VEGFR-2 kinase: Stability evaluation by molecular dynamic simulation.

The VEGFR-2 kinase specific intracellular signalling cascades leading to proliferation, migration, survival of endothelial cells and increased permeability of vessels which contributes to angiogenesis. ATP is essentially required by VEGFR-2 to perform phosphorylation of specific proteins and to maintain cascade downstream. Taxifolin (plant polyphenol) inhibit the VEGFR-2 kinase by binding at ATP-binding pocket revealed by molecular docking study. Further, stability of VEGFR-2 kinase-taxifolin complex is validated by molecular dynamic simulation. RMSD analysis for 3800 ps confirmed the stability of complex. Furthermore, thermodynamic stability was evidenced by stable total energy, potential energy, and, temperature and pressure profile. After MD simulation taxifolin was found to stably interact with pocket residues Cys 917 and Lys 1053 along with water molecules. These results suggest that therapeutic inhibition of VEGFR-2 by taxifolin as a type I inhibitor may be a promising ways to retard signaling cascade of specific proteins which play crucial role in cancer proliferation and also in development of second generation type II inhibitors.