Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Shock. 2012 Mar;37(3):312-8. doi: 10.1097/SHK.0b013e31823fe939.
Inflammation and oxidative stress play important roles in the pathogenesis of neurodegenerative disorders such as stroke, traumatic injury, Parkinson disease, and Alzheimer disease. Paeonol, a natural compound extracted from Moutan cortex, is a potent anti-inflammatory and antioxidative agent. The aim of this study was to investigate the neuroprotective mechanisms of paeonol on lipopolysaccharide (LPS)-induced inflammation in rat primary microglia and 6-hydroxydopamine-induced oxidative damage in cortical neurons. In LPS-treated microglia, paeonol attenuated the overexpression of inducible nitric oxide synthase and cyclooxygenase 2, leading to the decrease in nitric oxide and prostaglandin E2 production, respectively. Paeonol also suppressed LPS-induced phosphorylation of extracellular signal-regulated kinase and Jun N-terminal kinase. In addition, LPS-stimulated NADPH oxidase activation and reactive oxygen species production were attenuated by paeonol. Paeonol-induced upregulation of heme oxygenase 1 was also observed. Moreover, paeonol attenuated LPS-treated microglia culture medium-induced neuron cells death. Posttreatment with paeonol also reduced inflammatory responses in LPS-activated microglia and increased cell viability in LPS-treated microglia culture medium-treated neurons. Furthermore, in 6-hydroxydopamine-treated cortical neurons, paeonol not only decreased reactive oxygen species production but also increased cell viability, superoxide dismutase activity, and the antiapoptotic protein B-cell lymphoma 2 expression. Taken together, the present results suggest that paeonol might be a potential neuroprotective agent via inhibiting microglia-mediated inflammation and oxidative stress-induced neuronal damage.
炎症和氧化应激在神经退行性疾病的发病机制中起重要作用，如中风、创伤、帕金森病和阿尔茨海默病。丹皮酚是从牡丹皮中提取的一种天然化合物，是一种有效的抗炎和抗氧化剂。本研究旨在探讨丹皮酚对脂多糖（LPS）诱导的大鼠原代小胶质细胞炎症和 6-羟多巴胺诱导的皮质神经元氧化损伤的神经保护机制。在 LPS 处理的小胶质细胞中，丹皮酚减弱了诱导型一氧化氮合酶和环氧化酶 2 的过度表达，分别导致一氧化氮和前列腺素 E2 产生的减少。丹皮酚还抑制了 LPS 诱导的细胞外信号调节激酶和 Jun N 末端激酶的磷酸化。此外，丹皮酚还减弱了 LPS 刺激的 NADPH 氧化酶激活和活性氧的产生。还观察到丹皮酚诱导血红素加氧酶 1 的上调。此外，丹皮酚还减轻了 LPS 处理的小胶质细胞培养基诱导的神经元细胞死亡。丹皮酚的后处理还减轻了 LPS 激活的小胶质细胞中的炎症反应，并增加了 LPS 处理的小胶质细胞培养基处理的神经元中的细胞活力。此外，在 6-羟多巴胺处理的皮质神经元中，丹皮酚不仅减少了活性氧的产生，而且还增加了细胞活力、超氧化物歧化酶活性和抗凋亡蛋白 B 细胞淋巴瘤 2 的表达。综上所述，这些结果表明，丹皮酚可能通过抑制小胶质细胞介导的炎症和氧化应激诱导的神经元损伤而成为一种潜在的神经保护剂。
