Tanshinone I

Tanshinone I is an inhibitor of type IIA human recombinant sPLA₂ (IC₅₀=11 μM) and rabbit recombinant cPLA₂ (IC₅₀=82 μM). IC50 & Target: IC50: 11 μM (sPLA₂), 82 μM (cPLA₂)^[1]. In Vitro: Tanshinone I inhibits PGE₂ formation from LPS-induced RAW macrophages (IC₅₀=38 μM). When Tanshinone I is added simultaneously with LPS, this compound clearly inhibits PGE2 production (IC₅₀=38 μM) at 10-100 μM. Tanshinone I also reduces PGE2 production (IC₅₀=46 μM) when added after COX-2 is fully induced. The fact that Tanshinone I inhibits PGE2 production by pre-induced COX-2 strongly suggests that this compound may directly inhibit COX-2 activity and/or affect PLA₂ activity. When Tanshinone I is incubated with two different forms of phospholipase A₂ (PLA₂), it clearly inhibits sPLA₂ (IC₅₀=11 μM) in a concentration-dependent manner. Although being less potent, Tanshinone I also inhibits cPLA₂ (IC₅₀=82 μM)^[1]. In Vivo: Tanshinone I shows antiinflammatory activity in rat carrageenan-induced paw oedema and adjuvant-induced arthritis. In order to establish the anti-inflammatory activity of Tanshinone I, the classical animal models of acute and chronic inflammation [rat carrageenan (CGN)-induced paw oedema and rat adjuvant-induced arthritis (AIA)] are employed. When Tanshinone I is orally administered, it shows significant anti-inflammatory activity against CGN-induced paw oedema (47% inhibition at 160 mg/kg), while the IC₅₀ of indomethacin is 7.1 mg/kg. In AIA, Tanshinone I gives 27% inhibition of secondary inflammation at 18 day with an oral dose of 50 mg/kg/day, whereas prednisolone (5 mg/kg/day) shows potent inhibition (65%)^[1].