Tanshinlactone A from Salvia miltiorrhiza modulates interleukin-2 and interferon-gamma gene expression.
Salvia miltiorrhiza Bunge (Tanshen), a traditional Chinese herbal medicine, is popularly used to treat cardiovascular disorders. In the present study, effects of tanshinlactone A (C(16)H(12)O(4); M.W. 268), newly discovered from Salvia miltiorrhiza, on phytohemagglutinin (PHA)-stimulated cell proliferation were investigated in human peripheral blood mononuclear cells (PBMC). The results indicated that tanshinlactone A inhibited PBMC proliferation activated with PHA with an IC(50) of 15.6+/-1.9 microM. Cell viability test indicated that inhibitory effects of tanshinlactone A on PBMC proliferation were not through direct cytotoxicity. Furthermore, tanshinlactone A significantly decreased the interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) gene expression in PHA-activated PBMC. It reduced the phosphorylation of mitogen-activated protein kinases (MAPK) involving extracellular signal-regulated protein kinase (ERK), P38, and c-Jun NH(2)-terminal kinase (JNK) in PHA-treated PBMC. We suggested that the inhibitory effects of tanshinlactone A on PHA-induced PBMC proliferation, appeared to be mediated, at least in part, through reduction of MAPK activation and IL-2 and IFN-gamma production. Therefore, data demonstrate for the first time that tanshinlactone A is likely an immunomodulatory agent for PBMC.
Wu
M H
MH
Institute of Pharmacology, National Yang-Ming University, No. 155, Sec. 2, Li-Nung St., Shih-Pai, 112 Taipei, Taiwan, ROC.
Tsai
W J
WJ
Don
M J
MJ
Chen
Y C
YC
Chen
I S
IS
Kuo
Y C
YC
D000085:Acetates / Q000737:chemistry; D000328:Adult; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013997:Time Factors
D000085:Acetates; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D006586:Hexanes; D007376:Interleukin-2; D010616:Phenanthrenes; D010835:Phytohemagglutinins; D010936:Plant Extracts; C525188:tanshinlactone A; C007650:ethyl acetate; D007371:Interferon-gamma; D020929:Mitogen-Activated Protein Kinase Kinases