Tanshinones inhibit mast cell degranulation by interfering with IgE receptor-mediated tyrosine phosphorylation of PLCgamma2 and MAPK.
Recently we have isolated four active components from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) responsible for the anti-allergic activities. In this study, the molecular mechanism of action of tanshinones for the inhibition of mast cell degranulation was investigated by testing their effects on the signaling components of the high affinity IgE receptor FcepsilonRI. Activation of FcepsilonRI produced immediate tyrosine phosphorylation of Syk, mitogen-activated protein kinase extracellular signal-regulated kinase, ERK1/ERK2 (p44, p42), and phospholipase Cgamma2 (PLCgamma2). 5,16-Dihydrotanshinone-I possessed the strongest inhibitory effects on mast cell degranulation and markedly reduced FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma2. This suggests that tanshinones possibly exert their anti-allergic activities by affecting FcepsilonRI-mediated tyrosine phosphorylation of ERK and PLCgamma2. Abbreviations. FcepsilonRI:high affinity IgE receptor ERK:extracellular signal regulated kinase PLC: phospholipase C
Pharmacology Laboratory, College of Pharmacy, Chonnam National University, Kwang-Ju, Korea.
Hong-Seok
HS
Choi
Kyeong-Man
KM
Kim
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051966:Phospholipase C gamma; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D051381:Rats; D017455:Receptors, IgE / Q000187:drug effects*; D027561:Salvia miltiorrhiza; D010738:Type C Phospholipases / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D010616:Phenanthrenes; D010936:Plant Extracts; D017455:Receptors, IgE; D014443:Tyrosine; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma