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

Tan, Sheri-Ann; Yam, Hok Chai; Cheong, Siew Lee; Chow, Yoke Chan; Bok, Chui Yin; Ho, Jia Min; Lee, Pei Yin; Gunasekaran, Baskaran

doi:10.1016/j.sjbs.2021.12.037

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…Nevertheless, to date, only a single report exists on the inhibitory action of PPAD. In this work, leaf extract from Cratoxylum cochinchinense , constituting of mangiferin and vismiaquinone A, exhibited strong binding interaction with vital amino acid residues at the active site of PPAD in silico ( Tan et al., 2021 ). More research is needed to fully explore the potential of PPAD as a therapeutic drug target.…”

Section: Discussionmentioning

confidence: 97%

Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

Chow

Yam

Gunasekaran

et al. 2022

Front. Cell. Infect. Microbiol.

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Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.

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Section: Discussionmentioning

confidence: 97%

Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

Chow

Yam

Gunasekaran

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Our group evaluated the antioxidant activities of the methanolic leaf extracts of C. cochinchinense by using various antioxidant assays (Tan et al, 2021). The leaves were found to be antioxidant rich as they consisted of high phenolic and flavonoid contents, with the recorded values of 129.0 ± 2.55 mg GAE g -1 crude extract and 159.0 ± 2.15 mg QE g -1 crude extract, respectively.…”

Section: Antioxidantmentioning

confidence: 99%

Comprehensive Review of Cratoxylum Genus: Ethnomedical Uses, Phytochemistry, and Pharmacological Properties

Bok¹,

Low²,

Augundhooa³

et al. 2023

JTAS

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In the past, the Cratoxylum genus has often been utilized as traditional medicines, culinary ingredients, health supplements, as well as manufacturing materials. This flowering plant genus belongs to the family Hypericaceae and is classified into six species: Cratoxylum arborescens, Cratoxylum cochinchinense, Cratoxylum formosum, Cratoxylum glaucum, Cratoxylum maingayi, and Cratoxylum sumatranum. The Cratoxylum genus is native to Asia as a traditional medicinal plant. It is currently being translated into conventional therapeutics as a preventive agent for diabetes mellitus and cardiovascular diseases. The phytochemical analysis and pharmacological investigations on the Cratoxylum species have unveiled the wide spectrum of phytoconstituents, including xanthones, triterpenoids, flavonoids, and phenolic compounds. These compounds are attributed to their significant pharmacological effects, such as antibacterial, antifungal, antioxidant, antimalarial, anti-gastric ulcer, anti-HIV-1 reverse transcriptase, antidiabetic, and anticancer activities. These research findings have strengthened the foundation of the Cratoxylum genus as a traditional medicinal plant to be further developed and applied as selective therapeutic drugs for various ailments. This paper discusses the Cratoxylum genus regarding its traditional uses, phytochemical compounds, and pharmacological properties.

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“…Cratoxylum cochinchinense belongs to the family of Hypericaceae and grows naturally in Southern Asian countries ( Mustaqim and Amboupe, 2020 ). The roots and bark are both used in traditional Chinese medicine for the treatment of fevers, burns, and abdominal complications ( Thu et al, 2017 ; Tan et al, 2022 ). Xanthones, caged xanthones, triterpenoids, and flavonoids have been reported as bioactive constituents of C. cochinchinense ( Nguyen and Harrison, 1999 ; Mahabusarakam et al, 2006 ; Xiong et al, 2014 ; Li et al, 2018a ).…”

Section: Introductionmentioning

confidence: 99%

Investigation of bacterial neuraminidase inhibition of xanthones bearing geranyl and prenyl groups from Cratoxylum cochinchinense

Kim

Lee

et al. 2023

Front. Chem.

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Introduction: The root of Cratoxylum cochinchinense has been widely used as Chinese folk medicine to cure fevers, burns, and abdominal complications because it contains various bioactive metabolites such as xanthones, triterpenes, and flavonoids. In this study, we estimated bacterial neuraminidase inhibition with a series of xanthones from C. cochinchinense. BNA has connected to various biological functions such as pathogenic bacteria infection inflammatory process after infection and biofilm formation.Methods: The identification of xanthones (1–6) bearing geranyl and prenyl groups was established by spectroscopic data using UV, IR, NMR, and HREIMS. BNA inhibitory modes of isolated xanthones were investigated by Double-reciprocal plots. Moreover, the competitive inhibitor was evaluated the additional kinetic modes determined by kinetic parameters (k3, k4, and Kiapp). The molecular docking (MD) and molecular dynamics simulations (MDS) studies also provided the critical information regarding the role of the geranyl and prenyl groups against BNA inhibition.Results: A series of xanthones (1–6) appended prenyl and geranyl groups on the A-ring were isolated, and compounds 1–3 were shown to be new xanthones. The analogues within this series were highly inhibited with excellent affinity against bacterial neuraminidase (BNA). A subtle change in the prenyl or geranyl motif affected the inhibitory potency and behavior significantly. For example, the inhibitory potency and binding affinity resulting from the geranyl group on C4: xanthone 1 (IC50 = 0.38 μM, KA = 2.4434 × 105 L·mol−1) were 100-fold different from those of xanthone 3 (IC50 = 35.8 μM, KA = 0.0002 × 105 L·mol−1). The most potent compound 1 was identified as a competitive inhibitor which interacted with BNA under reversible slow-binding inhibition: Kiapp = 0.1440 μM, k3 = 0.1410 μM−1s−1, and k4 = 0.0203 min−1. The inhibitory potencies (IC50) were doubly confirmed by the binding affinities (KA).Discussion: This study suggests the potential of xanthones derived from C. cochinchinense as promising candidates for developing novel BNA inhibitors. Further research and exploration of these xanthones may contribute to the development of effective treatments for bacterial infections and inflammatory processes associated with BNA activity.

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

Cited by 4 publications

References 44 publications

Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

Comprehensive Review of Cratoxylum Genus: Ethnomedical Uses, Phytochemistry, and Pharmacological Properties

Investigation of bacterial neuraminidase inhibition of xanthones bearing geranyl and prenyl groups from Cratoxylum cochinchinense

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