Natural compounds from Danshen suppress the activity of hepatic stellate cells.
Danshen is an herbal medication frequently used in oriental medicine to treat liver or kidney malfunction. In the course of our studies, we observed that compounds purified from Danshen exhibit an inhibitory activity against Discoidin Domain Receptor 2 (DDR2) tyrosine kinase. Through this inhibition, these compounds also inhibited the growth of HSC T6 cells and suppressed the expression of alpha-smooth muscle actin and MMP2, as well as collagen synthesis, all of which are increased in activated liver stellate cells. Given that activation of liver stellate cells is the hallmark of liver fibrosis and that DDR2 plays a critical role in this activation, these results suggest that one of the pharmacological activities of Danshen extract that protects the liver is the inhibition of key cell-signaling kinases, such as DDR2, in liver stellate cells.
Oh
Seong Hwan
SH
Department of Family Medicine, Korea University, College of Medicine, Seoul, Korea.
Cho
Kyung-Hwan
KH
Yang
Beom-Seok
BS
Roh
Yong Kyun
YK
D000199:Actins / Q000378:metabolism; D001688:Biological Products / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D048430:Cell Shape; D003094:Collagen / Q000096:biosynthesis; D000070818:Discoidin Domain Receptors; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*
D000199:Actins; D001688:Biological Products; D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2