Molecular basis of the anti-inflammatory effects of terpenoids.
Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Among them, terpenoids (also referred to as terpenes), are the largest and most widespread class of secondary metabolites. They are found in higher plants, mosses, liverworts, algae and lichens, and also in insects, microbes or marine organisms. Some terpenoids have been used for therapeutic purposes for centuries as antibacterial, anti-inflammatory, antitumoral agents, and in recent decades research activity into the clinical potential of this class of compounds has increased continuously as a source of pharmacologically interesting agents. In the present review, molecular basis of the anti-inflammatory action of diterpenoids is presented with special emphasis on their ability to modulate critical cell signaling pathways involved in the inflammatory response of the body such as nuclear transcription factor-kappaB (NF-kappaB) activation. NF-kappaB plays an important role in the regulation of immune and inflammatory responses. Indeed, deregulated NF-kappaB expression is a characteristic phenomenon in several inflammatory diseases and NF-kappaB has become a major target in drug discovery. Hence, this article also introduces our recently elucidated findings about the potential of labdane diterpenoids as anti-inflammatory agents due to their ability to inhibit NF-kappaB. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.
de las Heras
B
B
Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Hortelano
Sonsoles
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000145:classification / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy; D004224:Diterpenes / Q000494:pharmacology*; D004358:Drug Therapy / Q000639:trends; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007165:Immunosuppression Therapy; D008519:Medicine, Traditional; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013729:Terpenes / Q000145:classification / Q000627:therapeutic use; D015533:Transcriptional Activation / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D016328:NF-kappa B; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha