Coompo Research Chemicals

Dihydrotanshinone is a lipophilic component of the medicinal herb Salvia miltiorrhiza (danshen) belonging to the family of Labiatae. The role of reactive oxygen species (ROS) and p38 mitogen-activated protein kinases (MAPK) in tanshinones-induced apoptosis was investigated in HepG2 cells in this study. The major tanshinones (cryptotanshinone, dihydrotanshinone, tanshinone I, tanshinone IIA), isolated from Salvia miltiorrhiza, inhibit cell growth and induce caspase-dependent apoptosis concentration-dependently, with dihydrotanshinone being the most potent. All four tanshinones were found to induce ROS generation, but only dihydrotanshinone can induce activation of p38 MAPK. The p38 MAPK activation by dihydrotanshinone was inhibited by N-acetyl cysteine pretreatment. It is thus concluded that ROS-mediated p38 MAPK activation plays a vital role in dihydrotanshinone-induced apoptosis in HepG2 cells.

Dihydrotanshinone relaxed the 5-HT-precontracted coronary artery rings with an IC50 value of 10.39 +/- 1.69µM. None of the above inhibitors or antagonists tested produced a significant change on the vasorelaxant effect of dihydrotanshinone, except 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one caused a 50% reduction. Pre-incubation of the artery rings for 10 min with dihydrotanshinone (100µM) abolished the CaCl2-induced vasoconstriction. These findings suggest that inhibition of Ca2+ influx in the vascular smooth muscle cells is important for the vasorelaxant effect of dihydrotanshinone, and it is independent of pathways involving the endothelium, muscarinic receptors, beta-adrenoceptors, adenylyl cyclase, and guanylyl cyclase.