Chiu Ya-Jen, Lee Chi-Mei, Lin Te-Hsien, Lin Hsuan-Yuan, Lee Shin-Ying, Mesri Mina, Chang Kuo-Hsuan, Lin Jung-Yaw, Lee-Chen Guey-Jen, Chen Chiung-Mei
* Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.
† Aintree University of Liverpool Hospital, Liverpool, UK.
Am J Chin Med. 2018 Oct 4:1-25. doi: 10.1142/S0192415X18500799.
Amyloid [Formula: see text] (A[Formula: see text]) plays a major role in the pathogenesis of Alzheimer's disease (AD). The accumulation of misfolded A[Formula: see text] causes oxidative and inflammatory damage leading to apoptotic cell death. Chinese herbal medicine (CHM) has been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of CHM extract Glycyrrhiza inflata (G. inflata) and its active constituents, licochalcone A and liquiritigenin in AD. We examined A[Formula: see text] aggregation inhibition, anti-oxidation and neuroprotection in Tet-On A[Formula: see text]-GFP 293/SH-SY5Y cells and anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 and LPS and interferon (IFN)-[Formula: see text] (LPS/IFN-[Formula: see text])-activated BV-2 cells. In addition, we applied conditioned media (CM) of BV-2 cells primed with LPS/IFN-[Formula: see text] to A[Formula: see text]-GFP SH-SY5Y cells to uncover the neuroprotective mechanisms. Our results showed that G. inflata extract and its two constituents displayed potentials of A[Formula: see text] aggregation inhibition and radical-scavenging in biochemical assays, A[Formula: see text] misfolding inhibition and reactive oxygen species (ROS) reduction in A[Formula: see text]-GFP 293 cells, as well as neurite outgrowth promotion, acetylcholinesterase inhibition and SOD2 up-regulation in A[Formula: see text]-GFP SH-SY5Y cells. Meanwhile, both G. inflata extract and its constituents suppressed NO, TNF-[Formula: see text], IL-1[Formula: see text], PGE2 and/or Iba1 productions in inflammation-stimulated RAW 264.7 or BV-2 cells. G. inflata extract and its constituents further protected A[Formula: see text]-GFP SH-SY5Y cells from BV-2 CM-induced cell death by ameliorating reduced BCL2 and attenuating increased IGFBP2, cleaved CASP3, BAD and BAX. Collectively, G. inflata extract, licochalcone A and liquiritigenin display neuroprotection through exerting anti-oxidative and anti-inflammatory activities to suppress neuronal apoptosis.
淀粉样蛋白β（Aβ）在阿尔茨海默病（AD）的发病机制中起主要作用。错误折叠的Aβ的积累会导致氧化和炎症损伤，进而导致细胞凋亡。中药已广泛应用于临床实践，用于治疗与氧化应激和神经炎症相关的神经退行性疾病。本研究考察了中药胀果甘草（Glycyrrhiza inflata）提取物及其活性成分甘草查尔酮A和甘草素在AD中的神经保护作用。我们检测了其对Tet-On Aβ-GFP 293/SH-SY5Y细胞中Aβ聚集的抑制作用、抗氧化作用和神经保护作用，以及对脂多糖（LPS）刺激的RAW 264.7细胞和LPS与干扰素（IFN）-γ（LPS/IFN-γ）激活的BV-2细胞的抗炎潜力。此外，我们将用LPS/IFN-γ预处理的BV-2细胞的条件培养基（CM）应用于Aβ-GFP SH-SY5Y细胞，以揭示其神经保护机制。我们的结果表明，胀果甘草提取物及其两种成分在生化分析中显示出抑制Aβ聚集和清除自由基的潜力，在Aβ-GFP 293细胞中抑制Aβ错误折叠和减少活性氧（ROS），以及在Aβ-GFP SH-SY5Y细胞中促进神经突生长、抑制乙酰胆碱酯酶和上调超氧化物歧化酶2（SOD2）。同时，胀果甘草提取物及其成分均抑制炎症刺激的RAW 264.7或BV-2细胞中一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、前列腺素E2（PGE2）和/或离子钙结合衔接分子1（Iba1）的产生。胀果甘草提取物及其成分通过改善BCL2降低和减轻胰岛素样生长因子结合蛋白2（IGFBP2）增加、半胱天冬酶3（CASP3）裂解、BAD和BAX上调，进一步保护Aβ-GFP SH-SY5Y细胞免受BV-2 CM诱导的细胞死亡。总体而言，胀果甘草提取物、甘草查尔酮A和甘草素通过发挥抗氧化和抗炎活性来抑制神经元凋亡，从而显示出神经保护作用。
