Inhibition of Porphyromonas gingivalis peptidyl arginine deiminase, a virulence factor, by antioxidant-rich Cratoxylum cochinchinense: In vitro and in silico evaluation

Porphyromonas gingivalis, the cause of periodontitis, is also linked to many systemic disorders due to its citrullination capability from a unique peptidyl arginine deiminase (PPAD). Protein citrullination is able to trigger an autoimmune response, increasing the severity of rheumatoid arthritis. The main objective of this study is to evaluate the inhibitory activity of Cratoxylym cochinchinense leaves extract towards the PPAD in vitro and in silico. Methanolic extract of Cratoxylum cochinchinense (CCM) was tested for total phenolic and flavonoid contents along with antioxidative assays. Inhibition of PPAD activities was conducted thereafter using recombinant PPAD in cell lysate. Phytocompounds postulated present in the CCM such as mangiferin, vismiaquinone A, delta-tocotrienol and alpha-tocotrienol and canophyllol were used as ligands in a simulated docking study against PPAD. Results obtained indicated high antioxidant potential in CCM while recording abundant phenolic (129.0 +/- 2.5495 mg GA/g crude extract) and flavonoid (159.0 +/- 2.1529 mg QE/g crude extract) contents. A dose-dependent inhibition of PPAD was observed when CCM was evaluated at various concentrations. CCM at 1 mg/mL exhibited citrulline concentration of 24.37 +/- 3.25 mM which was 5 times lower than the negative control (114.23 +/- 3.31 mM). Molecular docking simulation revealed that mangiferin and vismiaquinone A engaged in H-bonding and pi-pi interactions with important active site residues (Asp130, Arg152, Arg154 and Trp127) of PPAD and could be the potential phytochemicals that accounted for the inhibitory activities observed in the methanolic leaves extract. As such, CCM could be further explored for its therapeutic properties not only for periodontitis, but also for other systemic diseases like rheumatoid arthritis. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

This study evaluated the inhibitory activity of Cratoxylym cochinchinense leaves extract on PPAD. The results demonstrated that the extract exhibited high antioxidant potential and contained abundant phenolic and flavonoid compounds. In vitro and in vivo experiments showed dose-dependent inhibition of PPAD by the extract. Molecular docking simulation suggested potential phytochemicals responsible for the observed inhibitory activities.