7,8-dihydroxyflavone as a Neuroprotective agent in Ischemic Stroke through the Regulation of HIF-1α Protein

Author:

Dita Arviana Safira1,Yueniwati Yuyun2,Rahayu Masruroh3,Rizki Syaban Mokhamad Fahmi4

Affiliation:

1. Master Program in Biomedical Science, Faculty of Medicine, Brawijaya Univesity, Malang, Indonesia.

2. Department of Radiology, Saiful Anwar General Hospital, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

3. Department of Neurology, Saiful Anwar General Hospital, Faculty of Medicine, Brawijaya University, Malang, Indonesia.

4. Faculty of Medicine, Brawijaya Univesity, Malang, Indonesia.

Abstract

Stroke is one of the leading causes of death worldwide, particulary ischemic stroke. Tissue hypoxia due to decreased blood flow to the brain causes loss of energy, failure of homeostasis, and cell death. Pharmacological treatment based of the Food and Drug Administration is recombinant tissue plasminogen activator given intravenously. In addition, neuroprotectant agents given to prevent the expansion of the infarct area. Screening of a new compound as a drug candidate with in silico simulation to predict an interaction between 7,8-dihydroxiflavone (DHF) as a neuroprotective agent by stimulating a protein kinase through PI3K signaling pathway and inhibiting the activity of prolyl hydroxylase enzyme. The protein target was obtained from Protein Data Bank using the structure of PI3K (1E8X) and prolyl hydroxylase 2 (5OX6). Ligand structure of 7,8 dihydroxyflavone was obtained from PubChem. Those structures are analyzed for the pharmacokinetic and protein-ligand interaction with the help of software such as PyRx, PyMol and BIOVIA Discovery Studio. 7,8 DHF has a much lower bond energy (-8.6 Kcal/mol) when it binds to PI3K compared to the native ligand (-7.5 Kcal/mol). The same bond energy results between 7,8-DHF and its native ligands (-7.5 kcl/mol) when binds to prolyl hydroxylase. As an adaptive response to hypoxia caused by ischemic stroke, the findings are likely to boost the downstream signaling pathway and enhance HIF-1α expression.

Publisher

A and V Publications

Subject

Pharmacology (medical),Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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