Natural Products and their Role as Inhibitors of the Pro-Inflammatory Transcription Factor NF-κB

Abstract

Nuclear factor kappa B (NF-jB) is a transcription factor involved at the downstream stage of many signalling cascades and plays a crucial role in acute and chronic inflammatory conditions, induced and adaptive immunity, apoptosis and induced cell proliferation. For the last decade it has attracted intense research interest throughout the world. This review briefly expands on information on biogenic modulators of this transcription factor published since an earlier review in 2002 and goes into much more detail on parthenolide and curcumin -two natural products that have been at the centre of molecular and biochemical interest in identifying modulators of the NF-jB pathway. Both compounds have attracted considerable attention in regard to the mechanistic aspects of the compounds' action. An attempt to further develop some compounds into leads for new medicines are also discussed, focusing on an EU-funded project on anti-inflammatory natural products, mostly from medicinal plants used locally in selected Mediterranean regions.

Recent developments in anti‐inflammatory natural products

“…a-linolenic acid (18), docosahexaenoic acid (19), eicosapentaenoic acid (20), and 5-thia-8,11,14,17-eicosatetraenoic acid (21) (Fig. 3) have been reported to exhibit potential inhibitory effects on COX-2 and COX-1-catalyzed prostaglandin biosynthesis.…”

“…In 1899 acetylsalicylic acid (aspirin) was introduced as the first potent drug to treat rheumatic diseases. 16 Several reviews have been published recently on natural anti-inflammatory compounds but they have been restricted to either a particular target like lipoxygenases (LOXs), 17,18 arachidonic acid (AA) pathway, 19 nitric oxide (NO), 19 NF-kB, 19,20 TNF-a, 21 cytokines, chemokines, and adhesion molecules 22 or a particular class of compounds like polyphenols. All of the above reviews have described either some of natural products for a particular inflammation target or a very few selected compounds acting on different targets.…”

Ethnopharmacology and Drug Discovery

“…Therefore, the link with NF-kB signaling is an obvious one, and curcumin has repeatedly shown its inhibitory effects against the signaling cascade of activated NF-kB. 92 Finally, parthenolide from Tanacetum parthenium, Asteraceae (feverfew), is a potent inhibitor of NF-kB at low micromolar concentrations. Feverfew has long been used as a bitter tonic and antipyretic.…”

“…Various extraction solvents have been suggested and used and once more the strategy to be used in a project will depend on its specific requirements and goals of the project. 92 The main general recommendation is to start a dialogue between the scientists involved in the field work and those involved in the pharmacology and phytochemistry well before the collection of the samples starts.…”

A New Sterol from the Soft Coral Lobophytum crassum

“…Using various chromatographic separations, four sterols were isolated from the methanol extract of freeze-dried bodies of the soft coral L. crassum including one new compound, crassumsterol (1). The known compounds were elucidated as (22R,23R,24R)-5α,8α-epidioxy-22,23-methylene-24-methylcholest-6-en-3β-ol (2), 4 ergosterol peroxide (3), 5 and 3β-hydroxyandrost-5-en-17-one (4) 6 by analyzing the NMR and MS data in comparison with the literature values.…”