Abstract：
BACKGROUND: Alzheimer\'s disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it.
UNASSIGNED: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications.
METHODS: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aβ)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aβ in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aβ-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD.
RESULTS: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the \"four qi and five flavors\" system of TCM theory, the main pharmacological qualities were \"cold\" and \"sweet.\" Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aβ deposition in the brain of the CL2006 strain of C. elegans.
CONCLUSIONS: Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aβ deposition.
UNASSIGNED: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications.
METHODS: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aβ)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aβ in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aβ-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD.
RESULTS: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the \"four qi and five flavors\" system of TCM theory, the main pharmacological qualities were \"cold\" and \"sweet.\" Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aβ deposition in the brain of the CL2006 strain of C. elegans.
CONCLUSIONS: Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aβ deposition.
摘要：
背景：阿尔茨海默病（AD）是一种神经系统疾病。在患有这种疾病的人中，有相当大的医疗需求未得到满足。
■鉴于2型糖尿病（T2DM）和AD之间的联系，降血糖中药配方（TCMFs）可能是治疗AD的一种方法。我们调查了在低血糖TCMF中鉴定抗AD药物的可能性，并提出了另一种筛选AD药物的选择。
方法：转基因秀丽隐杆线虫的麻痹（C.线虫）菌株CL4176（由淀粉样β（Aβ）1-42聚集体引起）用于评估抗AD效果。使用5-羟色胺(5-HT)测定法测定由Aβ在转基因秀丽隐杆线虫菌株CL2355中的神经元表达诱导的毒性和神经变性。使用转基因Aβ表达菌株CL2006和转基因tau表达菌株BR5270来探索TCMFs对秀丽隐杆线虫中蛋白质表达的影响。然后，网络药理学用于确定作用机制。利用中药传承支持系统平台对处方模式进行调查,核心药物,和用于AD的低血糖TCMF的最佳组合。
结果：16种低血糖TCMFs延长了秀丽隐杆线虫CL4176菌株的PT50（半麻痹时间），减少了蠕虫瘫痪的比例。网络药理学结果表明，前列腺素-内过氧化物合酶2（PTGS2）和乙酰胆碱酯酶（AChE）是降糖TCMFs的主要靶点。富集通路分析显示胆碱能受体相关通路是TCMFs降糖的核心通路。根据中医理论的“四气五味”体系，主要的药理品质是“冷”和“甜”。“通过TCMISS的分析，我们发现黄芪-葛根药物对是降血糖TCMFs的重要中药。当以2:1(v/v)比率递送时,黄芪-葛根配对具有最强大的治疗效果。它减少了5-HT引起的瘫痪，秀丽隐杆线虫CL2006品系的AChE和PTGS2蛋白表达降低，Aβ沉积减少。
结论：黄芪葛根是一种有前途的治疗AD的药物，其机制可能是通过抑制AChE和PTGS2蛋白的产生,减少5-HT的摄入,然后减少Aβ沉积。
■鉴于2型糖尿病（T2DM）和AD之间的联系，降血糖中药配方（TCMFs）可能是治疗AD的一种方法。我们调查了在低血糖TCMF中鉴定抗AD药物的可能性，并提出了另一种筛选AD药物的选择。
方法：转基因秀丽隐杆线虫的麻痹（C.线虫）菌株CL4176（由淀粉样β（Aβ）1-42聚集体引起）用于评估抗AD效果。使用5-羟色胺(5-HT)测定法测定由Aβ在转基因秀丽隐杆线虫菌株CL2355中的神经元表达诱导的毒性和神经变性。使用转基因Aβ表达菌株CL2006和转基因tau表达菌株BR5270来探索TCMFs对秀丽隐杆线虫中蛋白质表达的影响。然后，网络药理学用于确定作用机制。利用中药传承支持系统平台对处方模式进行调查,核心药物,和用于AD的低血糖TCMF的最佳组合。
结果：16种低血糖TCMFs延长了秀丽隐杆线虫CL4176菌株的PT50（半麻痹时间），减少了蠕虫瘫痪的比例。网络药理学结果表明，前列腺素-内过氧化物合酶2（PTGS2）和乙酰胆碱酯酶（AChE）是降糖TCMFs的主要靶点。富集通路分析显示胆碱能受体相关通路是TCMFs降糖的核心通路。根据中医理论的“四气五味”体系，主要的药理品质是“冷”和“甜”。“通过TCMISS的分析，我们发现黄芪-葛根药物对是降血糖TCMFs的重要中药。当以2:1(v/v)比率递送时,黄芪-葛根配对具有最强大的治疗效果。它减少了5-HT引起的瘫痪，秀丽隐杆线虫CL2006品系的AChE和PTGS2蛋白表达降低，Aβ沉积减少。
结论：黄芪葛根是一种有前途的治疗AD的药物，其机制可能是通过抑制AChE和PTGS2蛋白的产生,减少5-HT的摄入,然后减少Aβ沉积。
