Fig 1.
General workflow of present work using network pharmacology and molecular docking analysis.
Table 1.
Prediction of Tinospora crispa know phytoconstituents and its druggability [16].
Fig 2.
PPI network of protein related insulin resistance in Homo sapiens.
The darker purple color and the bigger its nodes indicate higher degree of protein in the network.
Fig 3.
Docking sketch map of Tinoscorside A interaction with the crystal structure of PI3K.
(A) Pocket view of Tinoscorside A binding with PI3K active site. (B) 2D docking pattern of Tinoscorside A with amino acids hydrogen bonds LYS833 and ASP964.
Fig 4.
Structure of active constituents prediction of T. crispa as insulin sensitizer.
(A) Tinoscorside A (B) Makisterone C (C) Borapetoside A (D) β Sitosterol (E) Borapetoside B. All structures were drawn using MarvinSketch based on the previous studies [6].
Table 2.
Docking scores of the lowest ligand-protein binding energy of T. crispa constituents and significant proteins in insulin resistance.
Fig 5.
Molecular dynamics (MD) simulation analysis of Tinoscorside A with PI3K.
(A) root-mean square deviation (RMSD) of the complex against the initial crystal structure. The The blue graph represent RMSD of C alpha and the turquoise one represent RMSD of the side-chain; (B) root-mean square fluctuation (RMSF) of the C alpha residue; (C) The dynamics of hydrogen bond number along MD simulation; (D) the representative of the Tinoscorside A-PI3K complex after 24 ns MD simulation.
Fig 6.
(A) Intersection Venn diagram of T. crispa constituents and target protein related insulin resistance. There were 30 constituents of T. crispa that were predicted to be targeted to insulin resistance target protein. (B) Intersection Venn diagram between predicted target protein of T. crispa constituents, target proteins of insulin resistance pathogenesis, and high degree of connection value of target proteins of insulin resistance. There were 7 target proteins that meet the three intersections. In addition there were 22 proteins targeted by T. crispa constituents that were shown visually in Fig 6C. (C) Compound-target network of T. crispa constituents targeted to insulin resistance pathogenesis. The blue dots represent T. crispa constituents, the yellow dots represent protein targets, and the connecting lines represent compound-target interaction.
Fig 7.
Systematic prediction of 7 significant protein targets and therapeutic pathways of T. crispa constituents on insulin resistant.
The highlighted nodes represent the significant targets of T. crispa and other nodes represent their related target on insulin resistant. All the presented pathways were summarized by KEGG pathway database [21].