Alluri Ramesh, Kilari Eswar Kumar, Pasala Praveen Kumar, Kopalli Spandana Rajendra, Koppula Sushruta
Cognitive Science Research Initiative Lab., Department of Pharmacology, Vishnu Institute of Pharmaceutical Education and Research, Medak Dist., Narsapur 502313, India.
Department of Pharmacology, University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, India.
Life (Basel). 2023 Aug 4;13(8):1688. doi: 10.3390/life13081688.
Alzheimer's disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders, has proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured via passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured using ELISA kits, Western blotting, and immunostaining techniques. The data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers ( < 0.05~ < 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg, p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments and ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue. Considering the results obtained, DTZ might have a potential therapeutic role in treating and managing AD and related dementia pathologies due to its anti-dementia activity in SAD-type conditions in rats induced by ICV-STZ.
阿尔茨海默病（AD）是一种与年龄相关的神经精神疾病，也是进行性痴呆的常见病因。地尔硫䓬（DTZ）属于非二氢吡啶类苯并硫氮䓬类钙通道阻滞剂（CCB），临床上用于治疗心绞痛和其他心血管疾病，已被证明具有神经保护作用。在本研究中，研究了DTZ对脑室内注射链脲佐菌素（ICV-STZ）诱导的散发性AD（SAD）型大鼠模型的神经保护和抗痴呆作用。通过被动回避和莫里斯水迷宫任务测量ICV-STZ诱导的认知障碍。使用酶联免疫吸附测定试剂盒、蛋白质免疫印迹法和免疫染色技术测量大鼠脑组织中的抗氧化酶状态、促炎标志物和β-淀粉样蛋白（Aβ）表达。数据显示，大鼠脑室内注射ICV-STZ显著诱导认知缺陷，并改变氧化和促炎标志物水平（<0.05~<0.001）。在单次脑室内注射ICV-STZ（3mg/kg）前1小时，每天口服给予DTZ（10mg/kg、20mg/kg和40mg/kg），持续21天，可显著改善认知障碍，并改善ICV-STZ诱导的亚硝酸盐、促炎细胞因子（TNF-α和IL-1β）和抗氧化酶水平（超氧化物歧化酶、脂质过氧化和谷胱甘肽）的改变。此外，DTZ恢复了ICV-STZ诱导的脑组织中Aβ蛋白表达的增加。考虑到所获得的结果，由于DTZ在ICV-STZ诱导的大鼠SAD型疾病中具有抗痴呆活性，其可能在治疗和管理AD及相关痴呆病理方面具有潜在治疗作用。
