Inhibition of Porphyromonas gingivalis peptidyl arginine deiminase,a virulence factor,by antioxidant-rich Cratoxylum cochinchinense: In vitro and in silico evaluation |
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Authors: | Sheri-Ann Tan Hok Chai Yam Siew Lee Cheong Yoke Chan Chow Chui Yin Bok Jia Min Ho Pei Yin Lee Baskaran Gunasekaran |
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Affiliation: | 1. Department of Bioscience, Faculty of Applied Sciences, Tunku Abdul Rahman University College, Jalan Genting Kelang, 53300 Setapak, Kuala Lumpur, Malaysia;2. Department of Biotechnology, Faculty of Applied Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia;3. Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 57000 Bukit Jalil, Kuala Lumpur, Malaysia |
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Abstract: | 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, δ-tocotrienol and α-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. |
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Keywords: | Peptidyl arginine deiminase Anti-citrullination Mangiferin Vismiaquinone A ABTS" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" 2,2′-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt ACPA" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" Anti-citrullinated peptide antibodies BAEE" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" Benzoyl-L-arginine ethyl ester DNA" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" Deoxyribonucleic acid DPPH" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" 2,2-diphenyl-1-picrylhydrazyl DTT" },{" #name" :" keyword" ," $" :{" id" :" k0090" }," $$" :[{" #name" :" text" ," _" :" Dithiothreitol EDTA" },{" #name" :" keyword" ," $" :{" id" :" k0100" }," $$" :[{" #name" :" text" ," _" :" Ethylenediamine tetraacetic acid FRAP" },{" #name" :" keyword" ," $" :{" id" :" k0110" }," $$" :[{" #name" :" text" ," _" :" Ferric reducing antioxidant power GAE" },{" #name" :" keyword" ," $" :{" id" :" k0120" }," $$" :[{" #name" :" text" ," _" :" Gallic acid equivalence HPLC" },{" #name" :" keyword" ," $" :{" id" :" k0140" }," $$" :[{" #name" :" text" ," _" :" High performance liquid chromatography IPTG" },{" #name" :" keyword" ," $" :{" id" :" k0150" }," $$" :[{" #name" :" text" ," _" :" Isopropyl β- d-1-thiogalactopyranoside OPLS" },{" #name" :" keyword" ," $" :{" id" :" k0160" }," $$" :[{" #name" :" text" ," _" :" Optimized potentials for liquid simulations PAD" },{" #name" :" keyword" ," $" :{" id" :" k0170" }," $$" :[{" #name" :" text" ," _" :" Peptidylarginine deiminase PCR" },{" #name" :" keyword" ," $" :{" id" :" k0180" }," $$" :[{" #name" :" text" ," _" :" Polymerase chain reaction PDB" },{" #name" :" keyword" ," $" :{" id" :" k0190" }," $$" :[{" #name" :" text" ," _" :" Protein data bank PMSF" },{" #name" :" keyword" ," $" :{" id" :" k0200" }," $$" :[{" #name" :" text" ," _" :" Phenylmethylsulfonyl fluoride PPAD" },{" #name" :" keyword" ," $" :{" id" :" k0210" }," $$" :[{" #name" :" text" ," _" :" Porphyromonas gingivalis peptidylarginine deiminase QE" },{" #name" :" keyword" ," $" :{" id" :" k0220" }," $$" :[{" #name" :" text" ," _" :" Quercetin equivalence RA" },{" #name" :" keyword" ," $" :{" id" :" k0230" }," $$" :[{" #name" :" text" ," _" :" Rheumatoid arthritis SD" },{" #name" :" keyword" ," $" :{" id" :" k0240" }," $$" :[{" #name" :" text" ," _" :" Standard deviation SDS-PAGE" },{" #name" :" keyword" ," $" :{" id" :" k0250" }," $$" :[{" #name" :" text" ," _" :" Sodium dodecyl sulphate–polyacrylamide gel electrophoresis TFC" },{" #name" :" keyword" ," $" :{" id" :" k0270" }," $$" :[{" #name" :" text" ," _" :" Total flavonoid content TPC" },{" #name" :" keyword" ," $" :{" id" :" k0280" }," $$" :[{" #name" :" text" ," _" :" Total phenolic content TPTZ" },{" #name" :" keyword" ," $" :{" id" :" k0290" }," $$" :[{" #name" :" text" ," _" :" 2,4,6-Tripyridyl-S-triazine |
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