青叶苔藓(L.)珀耳斯。调节阿尔茨海默病中的多个神经保护靶点:来自计算和实验验证的证据。

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Laxmi Pattanashetti, Manoj M Donagannavar, Divya Jigalur, Vishal S Patil
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种以认知能力下降为特征的进行性神经退行性疾病,治疗选择有限,且与长期药物治疗相关的不良反应。本研究采用体内和体外相结合的方法,研究了平叶苔藓(Bryophyllum pinnatum)的神经保护作用。使用网络药理学和途径富集分析(KEGG, Cytoscape 3.10.1)来鉴定化合物-靶点网络关联。使用AutoDock Vina进行分子对接,并使用GROMACS进行200 ns的分子动力学(MD)模拟,以评估关键配体和靶点的稳定性。东莨菪碱(1 mg/kg, ig)诱导Wistar大鼠认知功能损伤。实验动物分别用白荆叶水酒精提取物(200和400 mg/kg,口服)和多奈哌齐(3 mg/kg,口服)治疗30 d。通过Morris水迷宫、高架迷宫、运动活动和握力测试评估认知和运动功能。生化测定乙酰胆碱酯酶(ACHE)活性、β-淀粉样蛋白(Aβ)水平、谷胱甘肽和脂质过氧化。脑组织组织病理学分析评估神经元完整性。计算机分析发现了多种参与ad相关通路的植物成分,包括MAPK、PI3K-Akt和胆碱能信号。地奥司明与乙酰胆碱(-10.3 kcal/mol)和MAO-B (-11.2 kcal/mol)具有较高的结合亲和性,通过分子动力学模拟证实其结合稳定。在体内,红草可显著改善认知能力、运动协调和抗氧化状态,同时降低Aβ聚集和ACHE活性(p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bryophyllum pinnatum (L.) Pers. Modulates Multiple Neuroprotective Targets in Alzheimer's Disease: Evidence from Computational and Experimental Validation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, with limited therapeutic options and adverse effects associated with long-term pharmacological treatments. This study investigated the neuroprotective potential of Bryophyllum pinnatum (B. pinnatum) through integrative in silico and in vivo approaches. Network pharmacology and pathway enrichment analyses (KEGG, Cytoscape 3.10.1) were used to identify compound-target network association. Molecular docking using AutoDock Vina and molecular dynamics (MD) simulations for 200 ns using GROMACS were executed to assess the stability of the key ligands and targets. Cognitive impairment was induced in Wistar rats using scopolamine (1 mg/kg, i.p.). Animals were treated with B. pinnatum hydroalcoholic leaf extract (200 and 400 mg/kg, p.o.) and donepezil (3 mg/kg, i.p.) for 30 days. Cognitive and motor functions were evaluated via Morris water maze, elevated plus maze, locomotor activity, and grip strength tests. Biochemical assays measured acetylcholinesterase (ACHE) activity, β-amyloid (Aβ) levels, glutathione, and lipid peroxidation. Histopathological analysis of brain tissue assessed neuronal integrity. In silico analyses identified multiple phytoconstituents involved in AD-relevant pathways, including MAPK, PI3K-Akt, and cholinergic signaling. Diosmin exhibited high binding affinities to ACHE (-10.3 kcal/mol) and MAO-B (-11.2 kcal/mol), with stable binding confirmed via MD simulations. In vivo, B. pinnatum significantly improved cognitive performance, motor coordination, and antioxidant status while reducing Aβ aggregation and ACHE activity (p < 0.05). Histological findings showed reduced neuronal degeneration and neuroinflammation. These results highlight the multitarget neuroprotective potential of B. pinnatum, with diosmin emerging as a promising plant-derived candidate for AD therapeutics.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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