Pharmacology Research Laboratory-II, Department of Pharmaceutical Science & Technology, Institute of Chemical Technology (University under Section 3 of UGC Act- 1956, Elite Status & Centre of Excellence-Govt. of Maharashtra, TEQIP Phase II Funded), Matunga (E), Mumbai, Maharashtra, 400019, India.
National Centre for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (NIRRH), Parel, Mumbai, India.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Mar;392(3):327-339. doi: 10.1007/s00210-018-1588-z. Epub 2018 Nov 28.
Alzheimer's disease (AD) is the leading neurodegenerative disorder with extracellular senile plaques and neurofibrillary tangles as the major hallmarks. The objective was to evaluate the effect of phloretin in a chronic model of sporadic AD by injecting aggregated form of Aβ25-35 peptide sequence intracerebroventricularly (icv) in Wistar rats. To achieve this, male Wistar rats were injected with aggregated Aβ25-35 peptide icv, followed by 21 days phloretin (2.5 mg/kg, 5 mg/kg) administration after recovery period. Barnes maze and elevated plus maze along with the biochemical estimation of antioxidant enzymes activities were conducted. The hippocampus region of the rat brains were stained with Congo red and Nissl stain. TNF-α was estimated in the brain homogenates using the ELISA assay. In this study, phloretin improved the spatial memory formation and retention in Barnes maze test. Additionally, phloretin alleviated the antioxidant defense biomarkers and thereby reduced oxidative stress, decreased TNF-α-mediated neuroinflammation. Furthermore, phloretin treatment showed decreased amyloid beta accumulation in the CA1 region and less number of pyknotic nuclei in the dentate gyrus of the Aβ25-35-injected rat brains. The above experimental findings evinced the promising role of phloretin in Aβ25-35-injected rats and which further envisage its potential to be explored in the treatment of AD.
阿尔茨海默病（AD）是一种主要的神经退行性疾病，其特征是细胞外老年斑和神经原纤维缠结。本研究的目的是通过向 Wistar 大鼠脑室内注射 Aβ25-35 肽聚集物来评估根皮苷在散发性 AD 慢性模型中的作用。为此，雄性 Wistar 大鼠脑室内注射 Aβ25-35 肽聚集物，在恢复期后给予根皮苷（2.5mg/kg、5mg/kg）21 天。进行巴恩斯迷宫和高架十字迷宫测试，以及抗氧化酶活性的生化评估。用刚果红和尼氏染色对大鼠脑内海马区进行染色。用 ELISA 法测定脑匀浆中的 TNF-α。在这项研究中，根皮苷改善了 Barnes 迷宫测试中的空间记忆形成和保留。此外，根皮苷减轻了抗氧化防御生物标志物，从而减少了氧化应激，降低了 TNF-α 介导的神经炎症。此外，根皮苷治疗显示 Aβ25-35 注射大鼠 CA1 区的淀粉样β积累减少，齿状回的固缩核数量减少。上述实验结果表明，根皮苷在 Aβ25-35 注射大鼠中具有有希望的作用，并进一步设想其在 AD 治疗中的潜在应用。
