ABSTRACT
Most inflammatory agents activate nuclear factor-kappaB (NF-kappaB), resulting in induction of genes coding for cytokines, chemokines, and enzymes involved in amplification and perpetuation of inflammation. Hypoestoxide (a bicyclo [9,3,1] pentadecane) is a diterpene from Hypoestes rosea, a tropical shrub in the family Acanthacea, several members of which are used in folk medicine in Nigeria. Here, we demonstrate that hypoestoxide (HE) abrogates the production of pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in lipopolysaccharide (LPS)-activated normal human peripheral blood mononuclear cells. Moreover, HE inhibits the production of nitric oxide (NO) by IL-1beta- or IL-17-stimulated normal human chondrocytes. In vivo, oral administration of HE to mice significantly ameliorated hind paw edema induced by antibodies to type II collagen plus LPS. Furthermore, topical administration of HE to mice also significantly inhibited phorbol ester-induced ear inflammation. The anti-inflammatory activity of HE may be due in part to its ability to inhibit NF-kappaB activation through direct inhibition of IkappaB kinase (IKK) activity. Thus, HE could be useful in treating various inflammatory diseases and may represent a prototype of a novel class of IKK inhibitors.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Diterpenes/pharmacology , Magnoliopsida/chemistry , Plants, Medicinal/chemistry , Protein Serine-Threonine Kinases/antagonists & inhibitors , Animals , Arthritis/chemically induced , Arthritis/drug therapy , Chondrocytes/drug effects , Chondrocytes/immunology , Diterpenes/chemistry , Edema/drug therapy , Female , Hindlimb/immunology , Humans , I-kappa B Kinase , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Mice , Mice, Inbred ICR , Nitric Oxide/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Entandrophragma angolense is a medicinal plant used in folk medicine against several diseases including peptic ulcer. Methyl angolensate was isolated from E. angolense by recrystallization from methanol. The needle-like crystals were characterized and tested on isolated rabbit jejunum, guinea pig ileum and the rat fundus strip. The compound was also evaluated on the gastrointestinal transit in mice. The results showed that the compound exerted significant concentration dependent inhibition of smooth muscle and reduced the propulsive action of the gastrointestinal tract in mice. The relaxation observed did not attenuate acetylcholine and histamine induced contractions, but was found to inhibit contractions induced by serotonin. It is therefore suggested that methyl angolensate may exert its activity on gastrointestinal smooth muscle via serotonergic mechanisms.
