BK21 Program, Department of Applied Life Sciences, Graduate School, Konkuk University, Chungju 27478, Korea.
BKplus GLOCAL Education Program of Nutraceuticals Development, Konkuk University, Chungju 27478, Korea.
Int J Mol Sci. 2022 Sep 1;23(17):9923. doi: 10.3390/ijms23179923.
Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many neurodegenerative disease progressions. Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism of action in microglial cells remain unknown. The current study investigates the possible anti-inflammatory effects and mechanisms of Makino ethanol extract and its steroidal saponin dioscin. Our in vitro study shows that rhizome ethanol extract (DNRE) and dioscin protect against lipopolysaccharide (LPS)-activated inflammatory responses in BV-2 microglial cells by inhibiting phosphorylation and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in the downregulation of pro-inflammatory cytokines and enzymes. Consistent with our previous report of dioscin-mediated enhancement of neurotrophic factors in dopaminergic cells, here we found that dioscin upregulates brain-derived neurotrophic factor (BDNF) and cAMP-response element binding protein (CREB) phosphorylation (pCREB) in the cerebral cortex and hippocampus regions of the mouse brain. Scopolamine treatment increased pro-inflammatory enzyme levels and reduced the expression of BDNF and pCREB in the hippocampus and cortex regions, which led to impaired learning and referencing memory in mice. Pre-treatment of dioscin for 7 days substantially enhanced mice performances in maze studies, indicating amelioration in cognitive deficits. In conclusion, DNRE and its active compound dioscin protect against neurotoxicity most likely by suppressing NF-κB phosphorylation and upregulating neurotrophic factor BDNF.
内源性或外源性损伤激活小胶质细胞可引起神经炎症，这是神经退行性疾病的常见现象。预防神经炎症可能改善许多神经退行性疾病的进展。黄精（DN）提取物可减轻肌肉萎缩和炎症性疾病；然而，其在小胶质细胞中的功效和作用机制尚不清楚。本研究探讨了黄精乙醇提取物及其甾体皂苷薯蓣皂苷元的抗炎作用及其机制。我们的体外研究表明，根茎乙醇提取物（DNRE）和薯蓣皂苷元可通过抑制核因子 kappa-轻链增强子的激活 B 细胞（NF-κB）的磷酸化和核转位，从而抑制脂多糖（LPS）激活的 BV-2 小胶质细胞炎症反应，从而下调促炎细胞因子和酶。与我们之前关于薯蓣皂苷元介导的多巴胺能细胞神经营养因子增强的报告一致，我们发现薯蓣皂苷元上调了小鼠大脑皮质和海马区的脑源性神经营养因子（BDNF）和 cAMP 反应元件结合蛋白（CREB）磷酸化（pCREB）。东莨菪碱处理增加了促炎酶的水平，并降低了海马和皮质区域的 BDNF 和 pCREB 的表达，导致小鼠学习和参考记忆受损。薯蓣皂苷元预处理 7 天可显著提高小鼠在迷宫研究中的表现，表明认知功能障碍得到改善。总之，DNRE 及其活性化合物薯蓣皂苷元通过抑制 NF-κB 磷酸化和上调神经营养因子 BDNF 来保护神经免受神经毒性。
