Dewi Ratih Tirto Sari, Gabriella Chandrakirana Krisnamurti

1-dehydrogingerdione, Senyawa volatil jahe sebagai agen sedatif subtitutif γ-aminobutyrate (GABA); Kajian biokomputasi

Introduction

1-dehydrogingerdione, senyawa volatil jahe sebagai agen sedatif subtitutif γ-aminobutyrate (gaba); kajian biokomputasi. Kaji potensi 1-dehydrogingerdione jahe sebagai agen sedatif subtitutif GABA melalui biokomputasi. Senyawa ini menunjukkan ikatan lebih kuat dibanding GABA dengan protein target.

Abstract

Gamma aminobutyrate (GABA) merupakan molekul penting dalam sistem saraf pusat. Ekspresi GABA yang tinggi menyebabkan abnormalitas sel saraf dan mengakibatkan beberapa penyakit termasuk penyakit mental. Penelitian ini bertujuan untuk menganalisis potensi tiga senyawa volatil yang terkandung di dalam jahe sebagai penenang melalui kajian biokomutasi. Pendekatan in silico digunakan dalam penelitian ini. Struktur senyawa volatil jahe didapatkan dari database PubChem dan struktur protein diperoleh dari database Protein Data Bank. Senyawa jahe, GABA diinteraksikan dengan protein target aminobutyrate aminotransferase dengan program Molegro virtual Docker 5 dan dianalisis menggunakan Discovery Studio ver 21.1.1. Senyawa 6-paradol, 6- gingerdione, dan 1-dehydrogingerdione berinteraksi dengan aminobutyrate aminotransferase pada beberapa sisi aktif, residu Phe217 teridentifikasi pada ketiga interaksi dan menunjukkan energi ikatan lebih rendah dari interaksi GABA dengan protein target. Jenis ikatan antara senyawa volatil jahe dan protein aminobutyrate aminotransferase yaitu ikatan hidrogen dan interaksi hidrofobik. Penelitian ini disimpulkan bahwa senyawa 1-dehydrogingerdione merupakan inhibitor aminobutyrate aminotransferase yang paling baik dan menunjukkan ikatan yang lebih kuat dari kompleks GABA-aminobutyrate aminotransferase. Kajian in vitro dan in vivo perlu dilakukan untuk analisis lebih lanjut.

Review

This study presents an intriguing in silico investigation into the potential of three volatile compounds from ginger – 6-paradol, 6-gingerdione, and 1-dehydrogingerdione – as inhibitors of aminobutyrate aminotransferase (GABA-T). The rationale is well-founded, addressing the critical role of GABA in the central nervous system and the implications of its dysregulation in neurological and mental health disorders. By aiming to identify compounds that could modulate GABA levels, the research proposes a novel approach to developing alternative sedative agents. The methodology employed standard biocomputational techniques, utilizing established databases for molecular structures and validated docking software to analyze compound-protein interactions. The key findings indicate that all three ginger compounds successfully interacted with aminobutyrate aminotransferase, with the Phe217 residue being consistently involved across all interactions. Significantly, these ginger compounds, particularly 1-dehydrogingerdione, exhibited lower binding energies compared to GABA's interaction with the target protein, suggesting a potentially stronger inhibitory effect on GABA-T. The identified interaction types, hydrogen bonds and hydrophobic interactions, are consistent with typical ligand-protein binding mechanisms. The conclusion that 1-dehydrogingerdione stands out as the most promising inhibitor within this set is a strong highlight of the computational analysis. While the computational predictions are compelling and provide a solid foundation, the inherent limitations of an exclusively in silico study must be acknowledged. The abstract itself appropriately concludes by emphasizing the critical need for further in vitro and in vivo validation. Future research should focus on experimentally confirming the inhibitory activity of 1-dehydrogingerdione on GABA-T, assessing its specificity, and evaluating its efficacy and safety profiles in biological systems. Investigating pharmacokinetic properties and potential off-target effects would also be crucial steps before considering this compound as a viable candidate for therapeutic development. This study serves as an excellent starting point, warranting dedicated experimental follow-up.

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