Clinic College of Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China.
Am J Chin Med. 2014;42(6):1399-410. doi: 10.1142/S0192415X14500888.
Oxymatrine, extracted from the herb Sophora alopecuraides L., was investigated to determine its anti-HBV immunomodulatory mechanism in vitro. Human peripheral lymphocytes were isolated from heparinized whole blood from 48 chronic hepatitis B (CHB) patients. The lymphocytes from each patient were divided into two groups according to pretreatment or no pretreatment with Oxymatrine in vitro. We examined the changes of expression and function of the toll-like receptor 9 (TLR9) signal transduction pathway in the peripheral lymphocytes with different treatment methods and investigated the synergism of Oxymatrine and the TLR9 ligand on antiviral cytokine secretions in vitro. The data showed Oxymatrine could induce antiviral cytokine secretions directly from the peripheral lymphocytes. For the TLR9 signal pathway, Oxymatrine not only augmented the expressions of TLR9 signal transduction molecules, but also activated the TLR9 signal function. This study has clearly demonstrated that TLR9 ligand could stimulate peripheral lymphocytes that have been pretreated with Oxymatrine. Furthermore, the quantity of antiviral cytokines secreted by the pretreated lymphocytes was greater than that of those without pretreatment. The interaction between the Oxymatrine and the TLR9 ligand appears to be synergistic. This study suggests Oxymatrine could be a strong immunomodulator, influence TLR9 signaling transduction, and synergistically improve the immune efficacy of the TLR9 ligand against CHB.
苦参碱,从苦参中提取,研究其体外抗乙肝病毒免疫调节机制。从 48 例慢性乙型肝炎(CHB)患者的肝素化全血中分离人外周血淋巴细胞。根据苦参碱体外预处理或不预处理,将每位患者的淋巴细胞分为两组。我们检测了不同处理方法外周淋巴细胞 Toll 样受体 9(TLR9)信号转导通路表达和功能的变化,并研究了苦参碱与 TLR9 配体在体外抗病毒细胞因子分泌中的协同作用。结果表明苦参碱能直接诱导外周淋巴细胞产生抗病毒细胞因子。对于 TLR9 信号通路,苦参碱不仅增强了 TLR9 信号转导分子的表达,而且激活了 TLR9 信号功能。本研究清楚地表明,TLR9 配体可以刺激已用苦参碱预处理的外周淋巴细胞。此外,预处理淋巴细胞分泌的抗病毒细胞因子的量大于未预处理的淋巴细胞。苦参碱与 TLR9 配体之间的相互作用似乎具有协同作用。本研究表明苦参碱可能是一种强大的免疫调节剂,影响 TLR9 信号转导,并协同提高 TLR9 配体对 CHB 的免疫疗效。