Abstract：
BACKGROUND: Patients with dementia are diagnosed with deficiency patterns and interior patterns in traditional Chinese medicine due to decreased physical strength, mental atrophy including cognitive function, and decreased motor function in the gastrointestinal tract. Since \"greater yin symptom\" in Shanghanlun has been interpreted as interior, deficiency, and cold pattern in traditional Chinese medicine, it is necessary to determine whether Geijigadaehwang-tang (GDT) has therapeutic effects on neurodegenerative diseases and the underlying mechanism if it has such effects.
OBJECTIVE: Trimethyltin (TMT), a neurotoxic organotin compound, has been used to induce several neurodegenerative diseases, including epilepsy and Alzheimer\'s disease. This study aimed to evaluate the therapeutic efficacy of GDT for TMT-induced hippocampal neurodegeneration and seizures and to determine the mechanisms involved at the molecular level.
METHODS: The main components of GDT were analyzed using ultra-performance liquid chromatography. TMT was used to induce neurotoxicity in microglial BV-2 cells and C57BL6 mice. GDT was administered at various doses to determine its neuroprotective and seizure inhibition effects. The inhibitory effects of GDT on TMT-induced apoptosis, inflammatory pathways, and oxidative stress pathways were determined in the mouse hippocampal tissues.
RESULTS: GDT contained emodin, chrysophanol, albiflorin, paeoniflorin, 6-gingerol, and liquiritin apioside. In microglial BV-2 cells treated with TMT, GDT showed dose-dependent neuroprotective effects. Oral administration of GDT five times for 2.5 days before and after TMT injection inhibited seizures at doses of 180 and 540 mg/kg and inhibited neuronal death in the hippocampus. In hippocampal tissues extracted from mice, GDT inhibited the protein expression of ionized calcium binding adaptor molecule 1, glial fibrillary acidic protein, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3, and phosphorylated nuclear factor (NF)-κB/total-NFκB ratio. Additionally, GDT inhibited the messenger RNA levels of tumor necrosis factor-α, inducible nitric oxide synthase, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, interleukin-1β, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1.
CONCLUSIONS: This study\'s results imply that GDT might have neuroprotective potential in neurodegenerative diseases through neuronal death inhibition and anti-inflammatory and antioxidant mechanisms.
OBJECTIVE: Trimethyltin (TMT), a neurotoxic organotin compound, has been used to induce several neurodegenerative diseases, including epilepsy and Alzheimer\'s disease. This study aimed to evaluate the therapeutic efficacy of GDT for TMT-induced hippocampal neurodegeneration and seizures and to determine the mechanisms involved at the molecular level.
METHODS: The main components of GDT were analyzed using ultra-performance liquid chromatography. TMT was used to induce neurotoxicity in microglial BV-2 cells and C57BL6 mice. GDT was administered at various doses to determine its neuroprotective and seizure inhibition effects. The inhibitory effects of GDT on TMT-induced apoptosis, inflammatory pathways, and oxidative stress pathways were determined in the mouse hippocampal tissues.
RESULTS: GDT contained emodin, chrysophanol, albiflorin, paeoniflorin, 6-gingerol, and liquiritin apioside. In microglial BV-2 cells treated with TMT, GDT showed dose-dependent neuroprotective effects. Oral administration of GDT five times for 2.5 days before and after TMT injection inhibited seizures at doses of 180 and 540 mg/kg and inhibited neuronal death in the hippocampus. In hippocampal tissues extracted from mice, GDT inhibited the protein expression of ionized calcium binding adaptor molecule 1, glial fibrillary acidic protein, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3, and phosphorylated nuclear factor (NF)-κB/total-NFκB ratio. Additionally, GDT inhibited the messenger RNA levels of tumor necrosis factor-α, inducible nitric oxide synthase, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, interleukin-1β, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1.
CONCLUSIONS: This study\'s results imply that GDT might have neuroprotective potential in neurodegenerative diseases through neuronal death inhibition and anti-inflammatory and antioxidant mechanisms.
摘要：
背景：痴呆患者因体力下降而被诊断为中医虚证模式和内证模式，精神萎缩，包括认知功能，胃肠道运动功能下降。由于“大阴症状”在尚汉伦被解释为内部，缺乏,和中医中的感冒模式，有必要确定Geijigadaehwang-tang（GDT）是否对神经退行性疾病具有治疗作用，以及具有这种作用的潜在机制。
目标：三甲基锡（TMT），一种神经毒性的有机锡化合物，已经被用来诱发几种神经退行性疾病，包括癫痫和阿尔茨海默病。本研究旨在评估GDT对TMT诱导的海马神经变性和癫痫发作的治疗效果，并确定分子水平的机制。
方法：采用超高效液相色谱法分析GDT的主要成分。TMT用于诱导小胶质细胞BV-2细胞和C57BL6小鼠的神经毒性。以各种剂量施用GDT以确定其神经保护和癫痫发作抑制作用。GDT对TMT诱导的细胞凋亡的抑制作用,炎症途径，并在小鼠海马组织中确定了氧化应激途径。
结果：GDT含有大黄素，大黄酚,albiflorin,芍药苷,6-姜辣素,和甘草苷。在用TMT处理的小胶质细胞BV-2细胞中，GDT显示出剂量依赖性的神经保护作用。在TMT注射之前和之后，口服GDT五次，持续2.5天，以180和540mg/kg的剂量抑制癫痫发作，并抑制海马中的神经元死亡。在从小鼠中提取的海马组织中，GDT抑制离子化钙结合衔接分子1、胶质纤维酸性蛋白的表达,核苷酸结合寡聚化结构域样受体家族含pyrin结构域的蛋白3和磷酸化核因子（NF）-κB/总NFκB比率。此外,GDT抑制肿瘤坏死因子-α的信使RNA水平,诱导型一氧化氮合酶，含有caspase募集结构域的凋亡相关斑点样蛋白，caspase-1,白介素-1β,核因子红细胞相关因子2和血红素加氧酶1。
结论：本研究结果提示GDT可能通过抑制神经元死亡、抗炎和抗氧化机制在神经退行性疾病中具有神经保护潜力。
目标：三甲基锡（TMT），一种神经毒性的有机锡化合物，已经被用来诱发几种神经退行性疾病，包括癫痫和阿尔茨海默病。本研究旨在评估GDT对TMT诱导的海马神经变性和癫痫发作的治疗效果，并确定分子水平的机制。
方法：采用超高效液相色谱法分析GDT的主要成分。TMT用于诱导小胶质细胞BV-2细胞和C57BL6小鼠的神经毒性。以各种剂量施用GDT以确定其神经保护和癫痫发作抑制作用。GDT对TMT诱导的细胞凋亡的抑制作用,炎症途径，并在小鼠海马组织中确定了氧化应激途径。
结果：GDT含有大黄素，大黄酚,albiflorin,芍药苷,6-姜辣素,和甘草苷。在用TMT处理的小胶质细胞BV-2细胞中，GDT显示出剂量依赖性的神经保护作用。在TMT注射之前和之后，口服GDT五次，持续2.5天，以180和540mg/kg的剂量抑制癫痫发作，并抑制海马中的神经元死亡。在从小鼠中提取的海马组织中，GDT抑制离子化钙结合衔接分子1、胶质纤维酸性蛋白的表达,核苷酸结合寡聚化结构域样受体家族含pyrin结构域的蛋白3和磷酸化核因子（NF）-κB/总NFκB比率。此外,GDT抑制肿瘤坏死因子-α的信使RNA水平,诱导型一氧化氮合酶，含有caspase募集结构域的凋亡相关斑点样蛋白，caspase-1,白介素-1β,核因子红细胞相关因子2和血红素加氧酶1。
结论：本研究结果提示GDT可能通过抑制神经元死亡、抗炎和抗氧化机制在神经退行性疾病中具有神经保护潜力。
