Kumar Suresh, Chowdhury Suman, Razdan Ajay, Kumari Deepa, Purty Ram Singh, Ram Heera, Kumar Pramod, Nayak Prasunpriya, Shukla Sunil Dutt
University School of Biotechnology, GGS Indraprastha University, New Delhi, India.
Department of Zoology, Jai Narain Vyas University, Jodhpur, India.
Front Pharmacol. 2021 Mar 2;11:595471. doi: 10.3389/fphar.2020.595471. eCollection 2020.
There is accumulating evidence showing that hyperglycemia conditions like diabetes possess a greater risk of impairment to the neuronal system because high glucose levels exacerbate oxidative stress, accumulation of amyloid-beta peptides, and mitochondrial dysfunction, and impair cognitive functions and cause neurodegeneration conditions like Alzheimer's diseases. Due to the extensive focus on pharmacological intervention to prevent neuronal cells' impairment induced by hyperglycemia, the underlying molecular mechanism that links between Diabetes and Alzheimer's is still lacking. Given this, the present study aimed to evaluate the protective effect of piperine on streptozotocin (STZ) induced hyperglycemia and candidate gene expression. In the present study, rats were divided into four groups: control (Vehicle only), diabetic control (STZ only), piperine treated (20 mg/kg day, i.p), and sitagliptin (Positive control) treated. The memory function was assessed by Morris water maze and probe test. After treatment, biochemical parameters such as HOMA index and lipid profile were estimated in the serum, whereas histopathology was evaluated in pancreatic and brain tissue samples. Gene expression studies were done by real-time PCR technique. Present data indicated that piperine caused significant memory improvement as compared to diabetic (STZ) control. The assessment of HOMA indices in serum samples showed that piperine and sitagliptin (positive control, PC) caused significant alterations of insulin resistance, cell function, and insulin sensitivity. Assessment of brain and pancreas histopathology shows significant improvement in tissue architecture in piperine and sitagliptin treated groups compared to diabetic control. The gene expression profile in brain tissue shows significantly reduced BACE1, PSEN1, APAF1, CASPASE3, and CATALASE genes in the piperine and sitagliptin (PC) treated groups compared to Diabetic (STZ) control. The present study demonstrated that piperine not only improves memory in diabetic rats but also reduces the expression of specific AD-related genes that can help design a novel strategy for therapeutic intervention at the molecular level.
越来越多的证据表明，像糖尿病这样的高血糖状况对神经系统造成损害的风险更大，因为高血糖水平会加剧氧化应激、β-淀粉样肽的积累和线粒体功能障碍，损害认知功能并导致如阿尔茨海默病等神经退行性疾病。由于广泛关注预防高血糖诱导的神经元细胞损伤的药物干预，糖尿病与阿尔茨海默病之间潜在的分子机制仍不明确。鉴于此，本研究旨在评估胡椒碱对链脲佐菌素（STZ）诱导的高血糖及候选基因表达的保护作用。在本研究中，大鼠被分为四组：对照组（仅给予赋形剂）、糖尿病对照组（仅给予STZ）、胡椒碱治疗组（20mg/kg/天，腹腔注射）和西他列汀（阳性对照）治疗组。通过莫里斯水迷宫和探针试验评估记忆功能。治疗后，测定血清中的生化参数如HOMA指数和血脂谱，同时对胰腺和脑组织样本进行组织病理学评估。通过实时PCR技术进行基因表达研究。目前的数据表明，与糖尿病（STZ）对照组相比，胡椒碱能显著改善记忆。血清样本中HOMA指数的评估表明，胡椒碱和西他列汀（阳性对照，PC）能显著改变胰岛素抵抗、细胞功能和胰岛素敏感性。脑和胰腺组织病理学评估显示，与糖尿病对照组相比，胡椒碱和西他列汀治疗组的组织结构有显著改善。脑组织中的基因表达谱显示，与糖尿病（STZ）对照组相比，胡椒碱和西他列汀（PC）治疗组中BACE1、PSEN1、APAF1、CASPASE3和CATALASE基因的表达显著降低。本研究表明，胡椒碱不仅能改善糖尿病大鼠的记忆，还能降低特定的阿尔茨海默病相关基因的表达，这有助于在分子水平上设计一种新的治疗干预策略。
