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Obesity has become a global issue that affects the emergence of various chronic diseases such as diabetes mellitus, dysplasia, heart disorders, and cancer. In this study, an integration method was developed between the metabolite profile of the active compound of Murraya paniculata and the exploration of the targeting mechanism of adipose tissue using network pharmacology, molecular docking, molecular dynamics simulation, and in vitro tests. Network pharmacology results obtained with the skyline query technique using a block-nested loop (BNL) showed that histone acetyltransferase p300 (EP300), peroxisome proliferator-activated receptor gamma (PPARG), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) are potential targets for treating obesity. Enrichment analysis of these three proteins revealed their association with obesity, thermogenesis, energy metabolism, adipocytokines, fat cell differentiation, and glucose homeostasis. Metabolite profiling of M. paniculata leaves revealed sixteen active compounds, ten of which were selected for molecular docking based on drug-likeness and ADME results. Molecular docking results between PPARG and EP300 with the ten active compounds showed a binding affinity value of ≤ -5.0 kcal/mol in all dockings, indicating strong binding. The stability of the protein-ligand complex resulting from docking was examined using molecular dynamics simulations, and we observed the best average root mean square deviation (RMSD) of 0.99 Å for PPARG with trans-3-indoleacrylic acid, which was lower than with the native ligand BRL (2.02 Å). Furthermore, the RMSD was 2.70 Å for EP300 and the native ligand 99E, and the lowest RMSD with the ligand (1R,9S)-5-[(E)-2-(4-Chlorophenyl)vinyl]-11-(5-pyrimidinylcarbonyl)-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one was 3.33 Å. The in vitro tests to validate the potential of M. paniculata in treating obesity showed that there was a significant decrease in PPARG and EP300 gene expressions in 3T3-L1 mature adipocytes treated with M. paniculata ethanolic extract starting at concentrations 62.5 μg/ml and 15.625 μg/ml, respectively. These results indicate that M. paniculata can potentially treat obesity by disrupting adipocyte maturation and influencing intracellular lipid metabolism. [ABSTRACT FROM AUTHOR]

Abstract Hyperglycaemia is one condition related to inflammation leading to insulin signalling impairment. This study was conducted to investigate the insulin sensitivity improvement of Sambiloto (Andrographis paniculata (Burm. f.)) Nees extract in insulin resistance-induced HepG2 (IR-HepG2) cells by stimulating insulin sensitivities and inhibiting inflammatory response. Sambiloto extract at 2 µg/mL revealed glucose uptake stimulation and up-regulating GLUT-2 and IRS-1 gene expression, and inhibited pro-inflammatory cytokine IL-6 gene expression in IR-HepG2 cells. Phytochemical analysis showed that the total phenolic level and andrografolide content of Sambiloto extract were 2.91 ± 0.04% and 1.95%, respectively. This result indicated that Sambiloto extract ameliorated insulin resistance in high glucose-induced IR-HepG2 cells via modulating the IRS-1/GLUT-2 pathway due to IL-6 inhibition. These findings suggested that Sambiloto extract had potency as an anti-inflammatory and insulin-resistance improvement in IR-HepG2 cells. [ABSTRACT FROM AUTHOR]

Hyperglycaemia is one condition related to inflammation leading to insulin signalling impairment. This study was conducted to investigate the insulin sensitivity improvement of Sambiloto ( Andrographis paniculata (Burm. f.)) Nees extract in insulin resistance-induced HepG2 (IR-HepG2) cells by stimulating insulin sensitivities and inhibiting inflammatory response. Sambiloto extract at 2 µg/mL revealed glucose uptake stimulation and up-regulating GLUT-2 and IRS-1 gene expression, and inhibited pro-inflammatory cytokine IL-6 gene expression in IR-HepG2 cells. Phytochemical analysis showed that the total phenolic level and andrografolide content of Sambiloto extract were 2.91 ± 0.04% and 1.95%, respectively. This result indicated that Sambiloto extract ameliorated insulin resistance in high glucose-induced IR-HepG2 cells via modulating the IRS-1/GLUT-2 pathway due to IL-6 inhibition. These findings suggested that Sambiloto extract had potency as an anti-inflammatory and insulin-resistance improvement in IR-HepG2 cells.