Rho iso‐alpha acids, a modified hop (Humulus lupulus) extract, inhibits protein kinases involved in autoimmune disease

Prostaglandin E2 (PGE2) has been implicated in many inflammatory diseases including rheumatoid arthritis, angiogenesis and cancer. Rho‐iso‐alpha acids (RIAA) inhibits synthesis of several prostaglandins (PGE2, PGD2, PGJ2 and TXB2) in lipopolysaccharide (LPS)‐activated murine macrophage cell line, RAW 264.7. Cell‐free enzyme assays reveal that RIAA does not inhibit prostaglandin production by directly inhibiting cyclooxygenase (COX) enzymatic activity. Instead, RIAA appears to inhibit the inducible forms of COX‐2 and nitric oxide synthase (iNOS) expression by inhibiting NF□B‐mediated signaling. Potential sites of RIAA inhibition of inflammatory signal transduction were investigated by screening RIAA against 208 human kinases. RIAA inhibits several of these kinases in a dose dependent manner and along various inflammatory signal transduction pathways. In particular, selective kinases implicated in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosis were among the top 10 human kinases inhibited in a dose dependent manner. Treatment of patients with various autoimmune diseases with an RIAA containing therapeutic showed dramatic improvement in pain scores. These results suggest that RIAA inhibits inflammation through multiple signal transduction mechanisms and may be of great therapeutic value in the treatment of autoimmune inflammatory diseases. (Supported by Metagenics Inc.)