Wu M H, Tsai W J, Don M J, Chen Y C, Chen I S, Kuo Y C
Institute of Pharmacology, National Yang-Ming University, No. 155, Sec. 2, Li-Nung St., Shih-Pai, 112 Taipei, Taiwan, ROC.
J Ethnopharmacol. 2007 Sep 5;113(2):210-7. doi: 10.1016/j.jep.2007.05.026. Epub 2007 Jun 2.
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.
丹参是一种传统的中草药，常用于治疗心血管疾病。在本研究中，我们研究了从丹参中新发现的丹参内酯A（C(16)H(12)O(4)；分子量268）对人外周血单个核细胞（PBMC）中植物血凝素（PHA）刺激的细胞增殖的影响。结果表明，丹参内酯A抑制PHA激活的PBMC增殖，IC(50)为15.6±1.9 microM。细胞活力测试表明，丹参内酯A对PBMC增殖的抑制作用不是通过直接细胞毒性实现的。此外，丹参内酯A显著降低PHA激活的PBMC中白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）的基因表达。它降低了PHA处理的PBMC中涉及细胞外信号调节蛋白激酶（ERK）、P38和c-Jun NH(2)-末端激酶（JNK）的丝裂原活化蛋白激酶（MAPK）的磷酸化。我们认为，丹参内酯A对PHA诱导的PBMC增殖的抑制作用，至少部分是通过降低MAPK激活以及IL-2和IFN-γ的产生介导的。因此，数据首次证明丹参内酯A可能是一种PBMC的免疫调节剂。
