Department of Geriatrics Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Int Immunopharmacol. 2011 Sep;11(9):1220-5. doi: 10.1016/j.intimp.2011.03.023. Epub 2011 Apr 13.
Microglial cells play an important role in mediating neuroinflammation in Alzheimer's disease (AD) by production of a series of proinflammatory mediators and clearance of Aβ peptides and senile plaques. Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of NF-κB activation. Here we investigated whether tetrandrine may affect the phagocytosis of microglia and the expression of cytokines and NF-κB in murine BV2 microglial cells. We found that fibrillar Amyloid-β (fAβ) induced phagocytosis of microglia and dramatically increased the levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) as well as the expression of phospho NF-κB p65 in microglia cultures. The treatment with tetrandrine resulted in downregulation of phospho NF-κB p65 expression and strikingly reduced the production of IL-1β and TNF-α. However, tetrandrine did not affect fAβ induced phagocytosis of microglia. In conclusion, tetrandrine can decrease microglial detriment of neurotoxicity while maintaining microglial benefit of neuroprotection. Tetrandrine may be an efficacious and promising remedy in the treatment of AD.
小胶质细胞通过产生一系列促炎介质和清除 Aβ 肽和老年斑，在阿尔茨海默病（AD）中介导神经炎症。汉防己甲素是从中药防己中分离得到的一种双苄基异喹啉生物碱，已被证明通过抑制 NF-κB 激活来降低促炎介质的表达。在这里，我们研究了汉防己甲素是否可能影响小胶质细胞的吞噬作用以及细胞因子和 NF-κB 在鼠 BV2 小胶质细胞中的表达。我们发现纤维状淀粉样蛋白-β（fAβ）诱导小胶质细胞吞噬作用，并显著增加小胶质细胞培养物中白细胞介素 1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的水平以及磷酸化 NF-κB p65 的表达。汉防己甲素处理导致磷酸化 NF-κB p65 表达下调，并显著减少 IL-1β 和 TNF-α 的产生。然而，汉防己甲素并不影响 fAβ 诱导的小胶质细胞吞噬作用。总之，汉防己甲素可以减少小胶质细胞对神经毒性的损害，同时保持小胶质细胞对神经保护的益处。汉防己甲素可能是治疗 AD 的一种有效且有前途的治疗方法。
