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.
Nam
Nguyen-Hai
NH
University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Vietnam. nhnam@etal.uri.edu
D000209:Acute-Phase Proteins / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols; D011971:Receptors, Immunologic / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
D000209:Acute-Phase Proteins; D000893:Anti-Inflammatory Agents; D001688:Biological Products; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004224:Diterpenes; D005419:Flavonoids; D006133:Growth Substances; D017705:Lignans; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D011971:Receptors, Immunologic; D012717:Sesquiterpenes; D014315:Triterpenes