■全球人口老龄化的升级加剧了老年糖尿病(SDM)作为随之而来的公共卫生问题的重要性。在老年糖尿病患者中普遍存在的氧化应激和慢性炎症级联反应显著放大了疾病进展和并发症发生率。在老年糖尿病的临床治疗中,中药(TCM)在提高血糖稳态和延缓并发症发生方面发挥着关键作用。尽管如此,在老年糖尿病治疗领域中,关于中医肾补肾药理机制与实验验证的整合存在明显的研究空白。
■本研究的目的是研究新肾气丸(SQP)治疗SDM的作用机制并进行实验评估。
■网络分析用于评估与SQP和SDM相关的目标途径。线粒体相关基因从MitoCarta3.0数据库获得,并与疾病和药物的共同靶基因相交,然后利用GeneMANIA数据库构建蛋白质-蛋白质相互作用(PPI)网络。使用高效液相色谱-串联质谱法(HPLC-MS/MS)定量测量SQP中的代表性化合物,以确保化合物的质量控制和定量分析。2型糖尿病小鼠(C57BL/6)模型用于研究SQP的药效学。通过包括体重和空腹血糖(FBG)的各种度量来评估SQP的降糖功效。为了阐明SQP对胰岛β细胞功能的调节作用,我们测量了口服葡萄糖耐量试验(OGTT),胰岛素组织化学染色和细胞凋亡检测,然后通过蛋白质印迹法评估糖尿病小鼠中胰岛素介导的磷酸肌醇3激酶(PI3K)/蛋白激酶A(Akt)/糖原合酶激酶3β(GSK-3β)途径。此外,我们观察细胞核的结构变化,胰岛β细胞的细胞质颗粒和线粒体。
■在这次调查中,我们共鉴定出1876个与老年糖尿病相关的基因,SQP的278个目标,和166个重叠的靶基因,主要富含与氧化应激反应相关的途径,肽反应,和氧气水平调制。此外,一项涉及1,136个人类线粒体基因和共病靶标的交叉分析得出了15个与线粒体相关的治疗靶标.SQP的质量控制评估和定量分析显示,主要存在五种浓度升高的化合物:Catalpol,肉桂醛,RehmanthinD,Trigonelline,还有丹皮酚.体内实验证明了值得注意的发现。相对于对照组,模型组小鼠体重和空腹血糖水平显著增加,伴随胰岛素分泌减少和胰岛细胞凋亡增加。此外,观察到β细胞核浓缩和线粒体cr消失,胰岛细胞中p-GSK-3β蛋白表达水平降低(p<0.05或p<0.01)。相反,给予SQP和Rg的治疗组显示上述蛋白质标志物的表达增强(p<0.05或p<0.01),在胰岛β细胞中保留线粒体cr结构。
■我们的发现表明,SQP可以通过减少胰岛细胞凋亡和抵抗氧化应激来改善糖尿病。这些胰岛素介导的PI3K/AKT/GSK-3β通路在此过程中起着重要的调节作用。
UNASSIGNED: The escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM\'s renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics.
UNASSIGNED: The objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment.
UNASSIGNED: Network analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet β cells.
UNASSIGNED: In this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, β-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3β protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet β cells.
UNASSIGNED: Our findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3β pathway plays an important regulatory role in this process.