Chemical Analysis of Cratoxylum Cochinchinense and its Inhibitory Potential Against Porphyromonas Gingivalis Peptidyl Arginine Deiminase (PPAD)

Ho, Jia Min (2020) Chemical Analysis of Cratoxylum Cochinchinense and its Inhibitory Potential Against Porphyromonas Gingivalis Peptidyl Arginine Deiminase (PPAD). Final Year Project (Bachelor), Tunku Abdul Rahman University College.

Text Ho Jia Min_Full Text.pdf Restricted to Registered users only Download (1MB)

Abstract

Cratoxylum cochinchinense is a native species in Southeast Asia widely used as a folk medicine. Previous antioxidant tests conducted by my colleague demonstrated that the methanolic extract from this plant possessed strong antioxidant activities which could be due to presence of phenolic compounds. We postulated that this plant extract may inhibit peptidyl arginine deiminase from Porphyromonas gingivalis (PPAD). This enzyme is reported to cause autoimmune diseases such as Rheumatoid Arthritis by citrullination. The major phenolic compounds in this plant, xanthone derivatives, might be potential natural inhibitors of PPAD. Main objectives of this project are 1) to determine the phytochemical constituents that contribute to the antioxidant property of this plant and 2) to explore the possibility of the plant to inhibit PPAD activity in silico. The methanolic extract of C. cochinchinense was analyzed with reversed phase High Performance Liquid Chromatography (RP-HPLC), Fourier-Transform Infrared Spectroscopy (FTIR) and CHNS elemental analysis. Bioactive compounds identified from C. cochinchinense were used as ligands to dock against PPAD using Autodock 4 in order to investigate possible interactions between the molecules. Results of RP-HPLC indicated that C. cochinchinense did not contain (+)-catechin, caffeic acid, chlorogenic acid and gallic acid which were reported earlier in other Cratoxylum species. FTIR spectrum displayed the functional groups of xanthone which proved its presence in the extract. Elemental analysis supported the result of FTIR by showing high amount of carbon and oxygen in the extract. For molecular docking, celebixanthone was suggested to be a strong inhibitor of PPAD because it interacted with cysteine-351, the main catalytic residue for PPAD as compared to beta-mangostin, cochinchinone A, mangiferin and vismiaquinone D. Further in vitro tests should be conducted to validate the inhibitory potential of C. cochinchinense against PPAD to inhibit its citrullination activity.