Analisis In Silico Senyawa Kimia dari Ekstrak Buah Mengkudu (Morinda citrifolia L.) terhadap PPAR-γ dan Uji In Vivo pada Ikan Zebra (Danio rerio) yang Berpotensi sebagai Antidiabetes

Abstract

Background: Diabetes mellitus (DM) is a chronic disease that occurs when the pancreas doesn’t produce enough insulin or when the body can’t use the insulin produced effectively. Pharmacological therapy can cause unwanted side effects, so non-pharmacological therapy is needed as an alternative treatment. One of them is noni (Morinda citrifolia L.) which is thought to contain chemical compounds such as flavonoids which are thought to have antidiabetic potential. Objective: This study aims to determine the secondary metabolite of noni fruit ethanol extract that could met the parameters of biological activity, physicochemical properties, pharmacokinetics, toxicity and has interactions with PPAR-γ receptors in silico and to determine the effect of noni ethanol extract in reduced blood glucose levels of zebrafish (Danio rerio). Method: In this in silico antidiabetic tested research, several stages were carried out, namely the analysis of chemical compounds of noni ethanol extract with LC-HRMS, prediction of biological activity with the PASS online website, physicochemistry with Lipinski rules, pharmacokinetics with the SwissADME website, toxicity with the ProTox-II website and molecular tethered with Autodock Vina. In in vivo antidiabetic tested, zebrafish was used as an experimental animal model, with the parameter of zebrafish blood glucose levels. Results: Based on the results of the research that has been carried out, from the results of the LC-HRMS test on the ethanol extract of noni fruit, 440 compounds were obtained, then eliminated based on mzCloud Best Match> 85% resulting in 72 compounds. After that, a literature search was carried out, so that 13 compounds were obtained that could be continued in silico tests. In silico, the chemical compounds obtained from the ethanol extract of noni fruit that has interactions with PPAR-γ receptors looked by at the binding affinity value and has similar amino acid residues with native ligands and comparators, namely 1,4-Dimethoxyanthraquinone. In vivo, the ethanol extract of noni fruit with a concentration of 400mg/2l could reduced KGD which is closed to the positive control group and has a significant difference with the negative control group (p < 0.0001). Conclusion: The chemical compounds of noni fruit ethanol extract have potential as antidiabetics, by fulfilled several tested parameters in silico and noni ethanol extract can reduce KGD in zebrafish in vivo.