Pharmacological Evaluation and In-Silico Study of Sabinene as a Potential Anti-Alzheimer’s Drug in AlCl3-Induced Rat Model via BACE-1 and GSK3β Modulation

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Pankti Parmar, Heena Chauhan, Palmi Modi, Dipa Israni
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引用次数: 0

Abstract

Alzheimer’s disease (AD) is a progressive and debilitating neurodegenerative disorder. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and glycogen synthase kinase-3β (GSK3β) contribute to Aβ plaque development, tau hyperphosphorylation, neurofibrillary tangles, and neuronal dysfunction in AD pathogenesis. This study aimed to investigate the neuroprotective potential of sabinene in an Aluminum chloride (AlCl3)-induced model of AD in male Wistar rats. Thirty male Wistar rats were randomly divided into six groups (n = 6 per group). Group I (control) received normal saline for 30 days. Groups II–V were administered only AlCl3 (100 mg/kg, orally) for 20 consecutive days to induce AD-like pathology, which was confirmed through behavioral assessments. Following induction, Group II (AD control) received 1% Tween 80; Group III (standard treatment) was administered rivastigmine (2.5 mg/kg); while Groups IV–VI received sabinene at doses of 5, 10, and 20 mg/kg, respectively, for 10 days 1 h prior to AlCl3. Behavioral evaluations were conducted on days 0, 20, and 31. On the 31st day, animals were sacrificed for biochemical and molecular analyses. In silico molecular docking studies revealed that sabinene exhibited a higher binding affinity towards AD-related targets (BACE1, GSK-3β, TACE, and AChE) compared to rivastigmine. In vivo, sabinene treatment significantly mitigated oxidative stress, restored antioxidant enzyme activities, reduced pro-inflammatory cytokine levels, AChE, BACE1, and GSK3β expression, and ameliorated histopathological alterations in the rat brain. Thus, sabinene exerts potent neuroprotective and disease-modifying effects in AlCl3-induced AD via AchE, BACE-1, and GSK3β Modulation.

Graphical Abstract

Sabinene通过BACE-1和GSK3β调控在alcl3诱导的大鼠模型中作为潜在抗阿尔茨海默病药物的药理学评价和计算机研究
阿尔茨海默病(AD)是一种进行性和衰弱性神经退行性疾病。β-位点淀粉样蛋白前体蛋白切割酶1 (BACE1)和糖原合成酶激酶3β (GSK3β)参与AD发病过程中Aβ斑块的形成、tau蛋白过度磷酸化、神经原纤维缠结和神经元功能障碍。本研究旨在探讨sabinene在氯化铝(AlCl3)诱导的雄性Wistar大鼠AD模型中的神经保护作用。30只雄性Wistar大鼠随机分为6组,每组n = 6只。第一组(对照组)给予生理盐水治疗30 d。II-V组仅给予AlCl3 (100 mg/kg,口服),连续20 d诱导ad样病理,通过行为评估证实。诱导后,第二组(AD对照)给予1% Tween 80;第三组(标准治疗)给予利瓦斯汀(2.5 mg/kg);IV-VI组分别以5、10和20 mg/kg剂量给药,比AlCl3早1 h,给药10天。分别于第0、20、31天进行行为评价。第31天处死动物进行生化和分子分析。硅分子对接研究表明,与雷瓦斯汀相比,sabinene对ad相关靶点(BACE1、GSK-3β、TACE和AChE)具有更高的结合亲和力。在体内,sabinene处理显著减轻了氧化应激,恢复了抗氧化酶活性,降低了促炎细胞因子水平、AChE、BACE1和GSK3β的表达,并改善了大鼠脑的组织病理学改变。因此,sabinene通过AchE、BACE-1和GSK3β调节在alcl3诱导的AD中发挥了有效的神经保护和疾病调节作用。图形抽象
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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