Hypoestoxide, a novel anti-inflammatory natural diterpene, inhibits the activity of IkappaB kinase.

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.

• Authors: E A Ojo-Amaize, P Kapahi, V N Kakkanaiah, T Takahashi, T Shalom-Barak, H B Cottam, A A Adesomoju, E J Nchekwube, O A Oyemade, M Karin, J I Okogun
• Journal: Cellular immunology (Cell Immunol) Vol. 209 Issue 2 Pg. 149-57 (May 01 2001) ISSN: 0008-8749 [Print] Netherlands
• PMID: 11446747 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Diterpenes
• Interleukin-1
• Interleukin-6
• Tumor Necrosis Factor-alpha
• hypoestoxide
• Nitric Oxide
• Protein Serine-Threonine Kinases
• CHUK protein, human
• Chuk protein, mouse
• I-kappa B Kinase
• IKBKB protein, human
• IKBKE protein, human
• Ikbkb protein, mouse
• Ikbke protein, mouse

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Arthritis (chemically induced, drug therapy)
• Chondrocytes (drug effects, immunology)
• Diterpenes (chemistry, pharmacology)
• Edema (drug therapy)
• Female
• Hindlimb (immunology)
• Humans
• I-kappa B Kinase
• Interleukin-1 (biosynthesis)
• Interleukin-6 (biosynthesis)
• Leukocytes, Mononuclear (drug effects, immunology)
• Magnoliopsida (chemistry)
• Mice
• Mice, Inbred ICR
• Nitric Oxide (biosynthesis)
• Plants, Medicinal (chemistry)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Tumor Necrosis Factor-alpha (biosynthesis)