Ding Feijia, Li Fan, Li Yunhong, Hou Xiaolin, Ma Yi, Zhang Nan, Ma Jiao, Zhang Rui, Lang Bing, Wang Hongyan, Wang Yin
Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Ningxia 750004, P.R. China.
Department of Neurology, The General Hospital of Ningxia Medical University, Ningxia 750004, P.R. China.
Exp Ther Med. 2016 Aug;12(2):823-828. doi: 10.3892/etm.2016.3413. Epub 2016 Jun 1.
Curcumin has anti-inflammatory and antioxidant properties and has been widely used to treat or prevent neurodegenerative diseases. However, the mechanisms underlying the neuroprotective effects of curcumin are not well known. In the present study, the effect of curcumin on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells was investigated using enzyme-linked immunosorbent assays of the culture medium and western blotting of cell lysates. The results showed that curcumin significantly inhibited the LPS-induced expression and release of heat shock protein 60 (HSP60) in the BV2 cells. The level of heat shock factor (HSF)-1 was upregulated in LPS-activated BV2 microglia, indicating that the increased expression of HSP60 was driven by HSF-1 activation. However, the increased HSF-1 level was downregulated by curcumin. Extracellular HSP60 is a ligand of Toll-like receptor 4 (TLR-4), and the level of the latter was increased in the LPS-activated BV2 microglia and inhibited by curcumin. The activation of TLR-4 is known to be associated with the activation of myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB, with the subsequent production of proinflammatory and neurotoxic factors. In the present study, curcumin demonstrated marked suppression of the LPS-induced expression of MyD88, NF-κB, caspase-3, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the microglia. These results indicate that curcumin may exert its neuroprotective and anti-inflammatory effects by inhibiting microglial activation through the HSP60/TLR-4/MyD88/NF-κB signaling wpathway. Therefore, curcumin may be useful for the treatment of neurodegenerative diseases that are associated with microglial activation.
姜黄素具有抗炎和抗氧化特性，已被广泛用于治疗或预防神经退行性疾病。然而，姜黄素神经保护作用的潜在机制尚不清楚。在本研究中，通过对培养基进行酶联免疫吸附测定以及对细胞裂解物进行蛋白质印迹分析，研究了姜黄素对脂多糖（LPS）刺激的BV2小鼠小胶质细胞的影响。结果表明，姜黄素显著抑制了LPS诱导的BV2细胞中热休克蛋白60（HSP60）的表达和释放。热休克因子（HSF）-1的水平在LPS激活的BV2小胶质细胞中上调，表明HSP60表达的增加是由HSF-1激活驱动的。然而，姜黄素下调了升高的HSF-1水平。细胞外HSP60是Toll样受体4（TLR-4）的配体，后者的水平在LPS激活的BV2小胶质细胞中升高，并被姜黄素抑制。已知TLR-4的激活与髓样分化初级反应88（MyD88）和核因子（NF）-κB的激活相关，随后产生促炎和神经毒性因子。在本研究中，姜黄素显著抑制了LPS诱导的小胶质细胞中MyD88、NF-κB、半胱天冬酶-3、诱导型一氧化氮合酶、肿瘤坏死因子-α、白细胞介素（IL）-1β和IL-6的表达。这些结果表明，姜黄素可能通过HSP60/TLR-4/MyD88/NF-κB信号通路抑制小胶质细胞激活，从而发挥其神经保护和抗炎作用。因此，姜黄素可能对治疗与小胶质细胞激活相关的神经退行性疾病有用。
