233630  Cryptotanshinone

Cryptotanshinone, a cell-permeable diterpene quinone and naturally occurring herbal constituent of Salvia miltiorrhiza Bunge (Danshen), is shown to inhibit the constitutive STAT3 Tyr⁷⁰⁵ phosphorylation in DU145 prostate cancer cells (>90% inhibition in 1 h at 7 µM) independent of the IL-6/JAK/STAT3 signaling pathway, resulting in a blockage of STAT3 dimerization, nuclear translocation, and STAT3-dependent transcription activity (by ~80% in 24 h at 7 µM). Cryptotanshinone is also reported to deplete cellular ATP level (by 75% in 12 h at 20 µM in C2C12 myotubes), resulting in an indirect activation of cellular AMPK pathways and an enhancement of insulin-stimulated cellular glucose uptake in C2C12 myotubes and 3T3-L1 adipocytes (by ~1.3- and 1.9-fold, respectively). Cryptotanshinone is demonstrated to be an orally active hypoglycemic agent in ob/ob mice, db/db mice, and ZDF rats in vivo (600 mg/kg/day).