Naturally occurring NF-kappaB inhibitors

NF-kappaB is a ubiquitous and well-characterised protein responsible for the regulation of complex phenomena, with a pivotal role in controlling cell signalling in the body under certain physiological and pathological conditions. Among other functions, NF-kappaB controls the expression of genes encoding the pro-inflammatory cytokines (e. g., IL-1, IL-2, IL-6, TNF-alpha, etc.), chemokines (e. g., IL-8, MIP-1alpha, MCP1, RANTES, eotaxin, etc.), adhesion molecules (e. g., ICAM, VCAM, E-selectin), inducible enzymes (COX-2 and iNOS), growth factors, some of the acute phase proteins, and immune receptors, all of which play critical roles in controlling most inflammatory processes. Since NF-kappaB represents an important and very attractive therapeutic target for drugs to treat many inflammatory diseases, including arthritis, asthma, and the auto-immune diseases, most attention has been paid in the last decade to the identification of compounds that selectively interfere with this pathway. Recently, a great number of plant-derived substances have been evaluated as possible inhibitors of the NF-kappaB pathway. These include a wide range of compound classess, such as lignans (manassantins, (+)-saucernetin, (-)-saucerneol methyl ether), sesquiterpenes (costunolide, parthenolide, celastrol, celaphanol A), diterpenes (excisanin, kamebakaurin), triterpenes (avicin, oleandrin), polyphenols (resveratrol, epigallocatechin gallate, quercetin), etc. In this mini-review we will discuss the medicinal chemistry of these compounds with regards to the NF-kappaB inhibition.