Computational Discovery of the Neuroprotective Potential of Karanjin Against Parkinson's Disease

IF 2 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY

ChemistrySelect Pub Date : 2025-10-08 DOI:10.1002/slct.202503043

Ragavendhar Gopinath, Chetan Ashok, Naveen Kumar Rajasekaran, Mahendran Sekar, Parasuraman Pavadai, Wong Ling Shing, Vetriselvan Subramaniyan, Srikanth Jeyabalan

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Abstract

Parkinson's disease, a degenerative neurological disorder, characterized by dopaminergic neuron loss, oxidative stress, and α-synuclein aggregation. Current therapies face limitations like side effects and lack of disease-modifying potential. This study investigates karanjin, a Furano flavonoid from Pongamia pinnata, as a putative multi-target neuroprotective agent using in silico approaches. ADME and toxicity profiling (SwissADME, ProTox-II) revealed karanjin's drug-likeness, blood-brain barrier permeability, and low hepatotoxicity. Network pharmacology identified SRC kinase, PI3K-Akt, and MAPK signalling as key targets, with karanjin modulating oxidative stress and neuroinflammation pathways. Molecular docking (Glide XP) demonstrated strong binding affinity (−100.1 kcal/mol) of karanjin to SRC kinase (PDB: 8HQA), stabilized by hydrogen bonds (Ser345, Gln275) and hydrophobic interactions (Tyr340, Leu393). Molecular dynamics simulations (100 ns) confirmed complex stability (RMSD < 2.5 Å), with consistent residue interactions (>70% occupancy). These results highlight karanjin's potential as a multi-target, BBB-penetrant neuroprotective activity.

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Karanjin抗帕金森病神经保护潜能的计算发现

帕金森病，一种退行性神经系统疾病，以多巴胺能神经元丧失、氧化应激和α-突触核蛋白聚集为特征。目前的治疗方法面临着副作用和缺乏改善疾病潜力等局限性。本研究利用计算机方法研究了来自桄子子籽的呋喃黄酮karanjin作为一种假定的多靶点神经保护剂。ADME和毒性分析（SwissADME, ProTox-II）显示karanjin具有药物相似性、血脑屏障通透性和低肝毒性。网络药理学鉴定出SRC激酶、PI3K-Akt和MAPK信号是关键靶点，karanjin调节氧化应激和神经炎症途径。分子对接（Glide XP）显示karanjin与SRC激酶（PDB: 8HQA）具有很强的结合亲和力（−100.1 kcal/mol），通过氢键（Ser345, Gln275）和疏水相互作用（Tyr340, Leu393）稳定。分子动力学模拟（100 ns）证实了配合物的稳定性（RMSD < 2.5 Å），具有一致的残基相互作用（占70%）。这些结果突出了karanjin作为多靶点、bbb渗透神经保护活性的潜力。

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来源期刊

ChemistrySelect Chemistry-General Chemistry

CiteScore

3.30

自引率

4.80%

发文量

1809

审稿时长

1.6 months

期刊介绍： ChemistrySelect is the latest journal from ChemPubSoc Europe and Wiley-VCH. It offers researchers a quality society-owned journal in which to publish their work in all areas of chemistry. Manuscripts are evaluated by active researchers to ensure they add meaningfully to the scientific literature, and those accepted are processed quickly to ensure rapid online publication.