Modulating TNF-α signaling with natural products

Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-α (TNF-α) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-α synthesis has been associated with the development of diabetes, septic shock, tumorigenesis, rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Currently, only protein-based drugs are available for the clinical inhibition of TNF-α activity. Small-molecule drugs that can regulate TNF-α levels or activity might provide a cost-effective alternative to protein-based therapeutics. This review briefly highlights the physiological and pathological roles of TNF-α, and covers those natural compounds capable of interfering with TNF-α activity.