Inhibition of inflammation and oxidative stress by Angelica dahuricae radix extract decreases apoptotic cell death and improves functional recovery after spinal cord injury

Inhibition of inflammation and oxidative stress by Angelica dahuricae radix extract decreases apoptotic cell death and improves functional recovery after spinal cord injury
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DOI:
10.1002/jnr.22734
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发表时间:
2012-01-01
影响因子:
4.2
通讯作者:
Yune, Tae Young
Yune, Tae Young
中科院分区:
医学3区
文献类型:
--
作者:
Moon, Youn Joo;Lee, Jee Youn;Yune, Tae Young

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炎症和氧化应激在脊髓损伤(SCI)的发病机制中起主要作用。在此,我们研究了白芷提取物对脊髓损伤后的神经保护作用。ADR提取物显著降低了脂多糖(LPS)激活的小胶质细胞系BV2细胞中促炎因子如肿瘤坏死因子- α (tnf - α)、白细胞介素-1 β (IL-1 β)、白细胞介素-6 (IL-6)、诱导型一氧化氮合酶(iNOS)和环氧合酶-2 (COX-2)的水平。ADR提取物还能显著降低lps激活BV2细胞的活性氧水平。为观察ADR提取物对脊髓损伤大鼠的神经保护作用,采用100 mg/kg剂量的ADR提取物连续14 d给药。ADR提取物治疗显著降低tnf - α、IL-1 β、IL-6、iNOS和COX-2水平。超氧阴离子(O2)和蛋白质硝化水平也显著降低。此外,ADR提取物可抑制脊髓损伤后小胶质细胞中p38丝裂原活化蛋白激酶的激活和促进生长因子的表达。此外,ADR提取物可显著抑制神经元和少突胶质细胞凋亡后caspase-3的激活,从而促进损伤后功能恢复。因此,我们的数据表明,ADR提取物通过减轻炎症和氧化应激提供神经保护,可以用作急性脊髓损伤的口服治疗药物。(c) 2011 Wiley期刊公司
Inflammation and oxidative stress play major roles in the pathogenesis after spinal cord injury (SCI). Here, we examined the neuroprotective effects of Angelica dahuricae radix (ADR) extract after SCI. ADR extract significantly decreased the levels of proinflammatory factors such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in a lipopolysaccharide (LPS)-activated microglial cell line, BV2 cells. ADR extract also significantly alleviated the level of reactive oxygen species in LPS-activated BV2 cells. To examine the neuroprotective effect of ADR extract after SCI, spinally injured rats were administered ADR extract orally at a dose of 100 mg/kg for 14 days. ADR extract treatment significantly reduced the levels of TNF-alpha, IL-1 beta, IL-6, iNOS, and COX-2. The levels of superoxide anion (O2) and protein nitration were also significantly decreased by ADR extract. In addition, ADR extract inhibited p38 mitogen-activated protein kinase activation and pronerve growth factor expression in microglia after SCI. Furthermore, ADR extract significantly inhibited caspase-3 activation following apoptotic cell death of neurons and oligodendrocytes, thereby improving functional recovery after injury. Thus, our data suggest that ADR extract provides neuroprotection by alleviating inflammation and oxidative stress and can be used as an orally administered therapeutic agent for acute SCI. (c) 2011 Wiley Periodicals, Inc.