Evaluation of Anti-Inflammatory Effects of Helminthostachys zeylanica Extracts via Inhibiting Bradykinin-Induced MMP-9 Expression in Brain Astrocytes
Evaluation of Anti-Inflammatory Effects of Helminthostachys zeylanica Extracts via Inhibiting Bradykinin-Induced MMP-9 Expression in Brain Astrocytes
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DOI：
10.1007/s12035-015-9511-9
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发表时间：
2016-11-01
影响因子：
5.1
通讯作者：
Lin, Chwan-Fwu
中科院分区：
文献类型：
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作者：
Hsieh, Hsi-Lung;Yang, Sien-Hung;Lin, Chwan-Fwu
蔬菜、水果和草药中的植物化学物质被认为可以降低几种主要疾病的风险，包括心血管或神经退行性疾病。本文报道了长穗蕨Helminthostachys zeylanica（L.）Hook.（Ophioglosaceae）几个世纪以来一直用于治疗炎症，并在几个国家作为民间药物。该植物已被证明具有一系列药用特性，包括抗氧化剂和抗炎活性。此外，在这些患有脑部炎症性疾病的患者的血液中发现基质金属蛋白酶-9（MMP-9）水平升高，这可能被认为是包括中枢神经系统（CNS）炎症在内的多种炎症性疾病的炎症生物标志物。以前，我们已经证明了缓激肽（BK）诱导MMP-9在脑星形胶质细胞表达的信号转导机制。在此，我们评估了H.泽兰提取物对BK诱导的脑星形胶质细胞MMP-9表达的影响及其机制结果表明，H.泽兰提取物E0、E1和E2显著降低BK诱导的脑星形胶质细胞（RBA-1细胞）中的MMP-9。这些H.泽兰提取物可抑制BK刺激的c-Src、Pyk 2和PKC（α/δ）磷酸化。此外，BK刺激的NADPH氧化酶（Nox）衍生的活性氧（ROS）的产生也被这些提取物预处理减弱，表明H。泽兰提取物具有抗氧化活性。我们进一步证明了H.泽兰提取物阻断MAPK的活化（例如，ERK 1/2和p38 MAPK）。zeylanica提取物可能通过脑星形胶质细胞中这些相关途径减少BK诱导的ROS依赖性MMP-9表达而具有抗炎活性。
Phytochemicals present in vegetables, fruits, and herbs are believed to reduce the risk of several major diseases including cardiovascular or neurodegenerative disorders. The roots of the fern Helminthostachys zeylanica (L.) Hook. (Ophioglossaceae) have been used for centuries in the treatment of inflammation and as a folk medicine in several countries. The plant has been shown to possess an array of medicinal properties, including antioxidants and anti-inflammatory activities. Moreover, a rising level of matrix metalloproteinase-9 (MMP-9) has been found in blood fluid of these patients suffering from brain inflammatory diseases, which may be considered an inflammatory biomarker in several inflammatory diseases including the central nervous system (CNS) inflammation. Previously, we have demonstrated the signaling mechanisms of bradykinin (BK)-induced MMP-9 expression in brain astrocytes. Herein, we evaluate the effects of H. zeylanica extracts on BK-induced MMP-9 expression in brain astrocytes and its influencing mechanism. The results showed that H. zeylanica extracts, including E0, E1, and E2 significantly reduce MMP-9 induced by BK in brain astrocytes (RBA-1 cells). These H. zeylanica extracts can inhibit BK-stimulated phosphorylation of c-Src, Pyk2, and PKC(alpha/delta). Moreover, BK-stimulated NADPH oxidase (Nox)-derived reactive oxygen species (ROS) generation has also been attenuated by pretreatment with these extracts, suggesting that the H. zeylanica extracts have an antioxidative activity. We further demonstrated that the H. zeylanica extracts blocked activation of MAPKs (e.g., ERK1/2 and p38 MAPK) by BK. These data indicated that the H. zeylanica extracts may be has anti-inflammatory activity by reducing BK-induced ROS-dependent MMP-9 expression via these related pathways in brain astrocytes.