本研究利用初代星狀膠質細胞進行體外培養之細胞模式,來了解以中草藥之純物質,包括Kaepferol-3,7-o-(α)-L-dirhamnoside (CO1, 由土肉桂萃取) 、Trimethyl-3,4- dehydrochebulate (PU3) 、Metyhylbrevifolin- carboxylate (PU6) (各由葉下株萃取)及andrographolide (AP2), 4-deoxy-11,12-dedihydro-andrographolide (AP3), (各由穿心蓮萃取) 等處理,對星狀細胞之影響。 本實驗第一部分使用腫瘤壞死因子- α (TNF - α)刺激活化星形膠質細胞,並且測試TNF - α與數種中草藥純物質共同處理24小時,是否有效降低cytokine分泌含量。初步篩選結果得葉下株純物質PU3、PU6 及穿心蓮純物質,AP2、AP3濃度小於20 μM下可降低TNF-alpha 誘導分泌之interleukin-6 (IL-6) 及TNF-alpha 量。第二部分進一步對AP2 、AP3測試是否能降低TNF-alpha 誘導產生的cytokine interleukin-1 (IL-1)、神經軸突再生抑制分子 chondroitin sulphate proteoglycan (CSPG) 及氧化壓力情形 (reactive oxygen species,ROS)。實驗結果得知此兩種穿心蓮純物質在濃度範圍AP2為0.1 μM,而AP3則是1 μM下可抑制IL-1、CSPG和ROS的分泌,這表明AP2和AP3可能可用於治療炎症相關的中樞神經系統疾病。 另外對此兩種物質作進一步研究是否有抗氧化功效,但結果顯示AP2和AP3在無細胞環境並無抗氧化功效,這表示AP2和AP3之抗氧化及降低發炎相關cytokine並不經由此機制。
In this project the effects on astrocytes are investigated for single compounds purified from Chinese Herb Extract medicine including Kaepferol-3,7-o-(α)-L-dirhamnoside, (CO1, from Cinnamomum osmophloeum Kaneh) 、Trimethyl-3,4-dehydrochebulate ( PU3, from Phyllanthus urinaria)、Metyhylbrevifolincarboxylate (PU6, from Phyllanthus Urinaria), and andrographolide (AP2)、14-deoxy-11,12-dedihydroandrographolide (AP3), both from Andrographis paniculata (Burm.f.) Nees.. Astrocytes play crucial role in the homeostasis and function of the central nervous system (CNS). They participate in the regulation of extracellular ions, neurotransmitters and growth factors, and in the transport and metabolism of nutrients, vitamins and amino acids. The CNS response to trauma, infection, inflammation, excitotoxicity, degenerative and dementia-type diseases manifests with accompanied reactive gliosis largely attributed to astrocytes. Astrocytes release of proinflammatory mediators include interleukin (IL)-1, interleukin 6 (IL-6), tumor necrosis factor (TNF)-α and reactive oxygen species (ROS). Proinflammatory cytokines can also cause neuronal cell death, both directly and indirectly via the induction of NO and free radicals. In addition, reactive astrogliosis generates increased expression of extracellular matrix (ECM) molecules, including chondroitin sulfate proteoglycans (CSPGs). CSPG overexpression is linked to glial scar formation, which inhibits neurite outgrowth and regeneration. Our results showed that firstly PU3, PU6, and AP2, AP3 inhibited TNF-alpha stimulated astrocytic IL-6 and TNF-alpha. Secondly when effects of AP2 and AP3 were investigated, AP2 and AP3 inhibited CSPG secretion, cellular ROS level, and TNF-alpha stimulated IL-1. AP2 is more effective than AP3. These results suggested the potential beneficial properties for AP compounds for the treatment of inflammation-related CNS disease.
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