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Pro-inflammatory actions of the platelet activating factor: relevance to rheumatoid arthritis

Sharma JN

Exp Pathol, 1991;43(1-2):47-50.
PMID: 1783046 DOI: 10.1016/s0232-1513(11)80141-6

The mechanisms causing inflammation in rheumatoid arthritis (RA) are not yet clearly known. They may be associated with different types of inflammatory cells and probably numerous mediators (SHARMA and MOHSIN 1990). Nowadays, the platelet activating factor (PAF) is discussed as an important mediator in RA.

Matched MeSH terms: Platelet Activating Factor/metabolism*
Clinacanthus nutans aqueous leaves extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway

Kow ASF, Khoo LW, Tan JW, Abas F, Lee MT, Israf DA, et al.

J Ethnopharmacol, 2023 Mar 01;303:116003.
PMID: 36464074 DOI: 10.1016/j.jep.2022.116003

ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach.
AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.
MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.
RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model.
CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

Matched MeSH terms: Platelet Activating Factor/metabolism; Platelet Activating Factor/therapeutic use
Therapeutic promises of ginkgolide A: A literature-based review

Sarkar C, Quispe C, Jamaddar S, Hossain R, Ray P, Mondal M, et al.

Biomed Pharmacother, 2020 Dec;132:110908.
PMID: 33254431 DOI: 10.1016/j.biopha.2020.110908

Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its inflammatory and immunological potentials. This review aims to sketch a current scenario on its therapeutic activities on the basis of scientific reports in the databases. A total 30 articles included in this review suggests that ginkgolide A has many important biological activities, including anti-inflammatory, anticancer, anxiolytic-like, anti-atherosclerosis and anti-atherombosis, neuro- and hepatoprotective effects. There is a lack of its toxicological (e.g. toxicity, cytotoxicity, genotoxicity and mutagenitcity) profile. In conclusion, ginkgolide A may be one of the potential therapeutic lead compounds, especially for the treatment of cardiovascular, hepatological, and neurological diseases and disorders. More studies are necessary on this hopeful therapeutic agent.

Matched MeSH terms: Platelet Activating Factor
The role of chemical mediators in the pathogenesis of inflammation with emphasis on the kinin system

Sharma JN, Mohsin SS

Exp Pathol, 1990;38(2):73-96.
PMID: 1971600

In recent years, numerous agents have been recognized as inflammatory mediators. In this review, however, we discuss only those having direct relevance to human inflammatory diseases These mediators are clinically important due to their proinflammatory properties such as vasodilatation, increased vascular permeability, pain and chemotaxis. They may lead to the fifth cardinal sign, loss of function in inflammatory diseases. Agonists and non-specific antagonists are used as pharmacological tools to investigate the inflammatory role of PGs, LTs, PAF, IL-1, histamine, complement, SP, PMN-leukocytes, and kallikrein-kininogen-kinin systems. Unfortunately, no compound is known which concurrently abolishes all actions and interactions of inflammatory mediators. Therefore it would be highly useful to promote efforts in developing selective and competitive antagonists against proinflammatory actions of these chemical mediators. This may help to a better understanding of the pathogenesis of inflammatory reactions, and it may also be useful for the therapy of inflammatory diseases.

Matched MeSH terms: Platelet Activating Factor/physiology
Molecular docking study on platelet-activating factor antagonistic activity of bioactive compounds isolated from Guttiferae and Ardisia species

Jasamai M, Jalil J, Jantan I

Nat Prod Res, 2015;29(11):1055-8.
PMID: 25332053 DOI: 10.1080/14786419.2014.971317

A handful of bioactive compounds from plants have been reported to possess platelet-activating factor (PAF) antagonist activity. However, their mode of action is not well understood. Selected bioactive compounds that exhibit PAF antagonist activity and synthetic PAF antagonists were subjected to docking simulations using the MOE 2007.09 software package. The docking study of PAF antagonists was carried out on the PAF receptor (PAFR) protein which involves in various pathological responses mediated by PAF. The docking results revealed that amentoflavone (3) showed good interactions with the PAFR model where the flavone and phenolic moieties were mostly involved in these interactions. Knowledge on PAF antagonists' interactions with the PAFR model is a useful screening tool of potential PAF antagonists prior to performing PAF inhibitory assay.

Matched MeSH terms: Platelet Activating Factor/antagonists & inhibitors*
Platelet-activating factor (PAF) receptor binding activity of the roots of Enicosanthellum pulchrum

Nordin N, Jalil J, Jantan I, Murad S

Pharm Biol, 2012 Mar;50(3):284-90.
PMID: 22103812 DOI: 10.3109/13880209.2011.602416

Enicosanthellum pulchrum (King) Heusden (Annonaceae) is a coniferous tree that is confined to mountain forests. The chemical constituents of this species have been studied previously; however, its biological activity has never been investigated before and is reported here for the first time.

Matched MeSH terms: Platelet Activating Factor/metabolism
Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants

Jantan I, Rafi IA, Jalil J

Phytomedicine, 2005 Jan;12(1-2):88-92.
PMID: 15693713

Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).

Matched MeSH terms: Platelet Activating Factor/antagonists & inhibitors*
Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding

Jantan I, Pisar M, Sirat HM, Basar N, Jamil S, Ali RM, et al.

Phytother Res, 2004 Dec;18(12):1005-7.
PMID: 15742349

Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors.

Matched MeSH terms: Platelet Activating Factor/antagonists & inhibitors*
Fulltext Inhibitory effects of acetylmelodorinol, chrysin and polycarpol from Mitrella kentii on prostaglandin E₂ and Thromboxane B₂ production and platelet activating factor receptor binding

Saadawi S, Jalil J, Jasamai M, Jantan I

Molecules, 2012;17(5):4824-35.
PMID: 22538486 DOI: 10.3390/molecules17054824

Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using ³H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE(2) production (IC₅₀ value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB₂ production with IC₅₀ values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC₅₀ values of 24.3 and 24.5 µM, respectively.

Matched MeSH terms: Platelet Activating Factor/metabolism
Fulltext Platelet-activating factor (PAF) antagonistic activity of a new biflavonoid from Garcinia nervosa var. pubescens King

Jalil J, Jantan I, Ghani AA, Murad S

Molecules, 2012 Sep 10;17(9):10893-901.
PMID: 22964504 DOI: 10.3390/molecules170910893

The methanol extract of the leaves of Garcinia nervosa var. pubescens King, which showed strong inhibitory effects on platelet-activating factor (PAF) receptor binding, was subjected to bioassay-guided isolation to obtain a new biflavonoid, II-3,I-5, II-5,II-7,I-4',II-4'-hexahydroxy-(I-3,II-8)-flavonylflavanonol together with two known flavonoids, 6-methyl-4'-methoxyflavone and acacetin. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit PAF receptor binding to rabbit platelets using ³H-PAF as a ligand. The biflavonoid and acacetin showed strong inhibition with IC₅₀ values of 28.0 and 20.4 µM, respectively. The results suggest that these compounds could be responsible for the strong PAF antagonistic activity of the plant.

Matched MeSH terms: Platelet Activating Factor/antagonists & inhibitors*