Research articles
ScienceAsia 50 (2024):ID 2024073 1-9 |doi:
10.2306/scienceasia1513-1874.2024.073
Inhibitory activity of mangiferin against Porphyromonas
gingivalis gingipain K, a causal agent of Alzheimer's disease:
An integrated in vitro and in silico study
Sheri-Ann Tana,*, Jia Hui Laib, Su Ying Leea, Xin Yan Loha, Shi Ruo Tongc, Wei Quan Ongb, Muhamad Zakwan Hafiq bin Abdul Razakb, Yien Yien Onga, Siew Lee Cheongb,*
ABSTRACT: Gingipain K, a virulence protein from Porphyromonas gingivalis, is involved in the pathogenesis of
Alzheimer?s disease. Hence, this research aimed to investigate the potential of methanolic extract of Cratoxylum
cochinchinese leaves (CME) and the pure compound, mangiferin, in inhibiting this protein. The inhibition of gingipain K
activity was measured based on the cleaving potential of this enzyme towards Ac-Lys-pNA, a synthetic peptide substrate
containing a chromogenic leaving group. Phytocompounds present in CME were then used as ligands in a simulated
docking study with gingipain K. Results indicated that the CME was a potential inhibitor of gingipain K, reducing the
protein activity in a dose dependent manner compared with the untreated control. Molecular docking analysis of the
phytocompounds revealed mangiferin as the best inhibitor with the highest docking score. The studies showed that
mangiferin engaged in H-bonding and ?-? interactions with important active site residues in vicinity, such as Asp388,
Gly445, Cys477, Trp391, and Trp513. The compound, when tested in the in vitro gingipain K inhibition assay, produced
an IC50 of 134.20 ?M, which was close to the IC50 of the positive control, TLCK (IC50 = 108.40 ?M). The additional
bioactivity of mangiferin as gingipain K inhibitor as reported here together with its known neuroprotective activity shall
encourage further investigation of this molecule in the treatment of such a debilitating illness, the Alzheimer?s disease.
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| a |
Department of Bioscience, Faculty of Applied Sciences, Tunku Abdul Rahman University of Management and
Technology, Setapak, Kuala Lumpur 53300 Malaysia |
| b |
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil,
Kuala Lumpur 57000 Malaysia |
| c |
Department of Physical Science, Faculty of Applied Sciences, Tunku Abdul Rahman University of Management and
Technology, Setapak, Kuala Lumpur 53300 Malaysia |
* Corresponding author, E-mail: tansw@tarc.edu.my, CheongSiewLee@imu.edu.my
Received 12 Jun 2023, Accepted 8 May 2024
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