1. Network pharmacology of bioactives from Sorghum bicolor with targets related to diabetes mellitus.
- Author
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Oh KK, Adnan M, and Cho DH
- Subjects
- Binding Sites, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Fatty Acid Binding Protein 3 antagonists & inhibitors, Fatty Acid Binding Protein 3 genetics, Fatty Acid Binding Protein 3 metabolism, Fatty Acid-Binding Proteins antagonists & inhibitors, Fatty Acid-Binding Proteins genetics, Fatty Acid-Binding Proteins metabolism, Hypoglycemic Agents isolation & purification, Hypoglycemic Agents pharmacology, Liver X Receptors antagonists & inhibitors, Liver X Receptors genetics, Liver X Receptors metabolism, Molecular Docking Simulation, PPAR alpha antagonists & inhibitors, PPAR alpha genetics, PPAR alpha metabolism, PPAR delta antagonists & inhibitors, PPAR delta genetics, PPAR delta metabolism, PPAR gamma antagonists & inhibitors, PPAR gamma genetics, PPAR gamma metabolism, Phytochemicals isolation & purification, Phytochemicals pharmacology, Plant Extracts chemistry, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Signal Transduction, Sterols isolation & purification, Sterols pharmacology, Structure-Activity Relationship, Gene Expression Regulation drug effects, Gene Regulatory Networks drug effects, Hypoglycemic Agents chemistry, Phytochemicals chemistry, Sorghum chemistry, Sterols chemistry
- Abstract
Background: Sorghum bicolor (SB) is rich in protective phytoconstituents with health benefits and regarded as a promising source of natural anti-diabetic substance. However, its comprehensive bioactive compound(s) and mechanism(s) against type-2 diabetes mellitus (T2DM) have not been exposed. Hence, we implemented network pharmacology to identify its key compounds and mechanism(s) against T2DM., Methods: Compounds in SB were explored through GC-MS and screened by Lipinski's rule. Genes associated with the selected compounds or T2DM were extracted from public databases, and the overlapping genes between SB-compound related genes and T2DM target genes were identified using Venn diagram. Then, the networking between selected compounds and overlapping genes was constructed, visualized, and analyzed by RStudio. Finally, affinity between compounds and genes was evaluated via molecular docking., Results: GC-MS analysis of SB detected a total of 20 compounds which were accepted by the Lipinski's rule. A total number of 16 compounds-related genes and T2DM-related genes (4,763) were identified, and 81 overlapping genes between them were selected. Gene set enrichment analysis exhibited that the mechanisms of SB against T2DM were associated with 12 signaling pathways, and the key mechanism might be to control blood glucose level by activating PPAR signaling pathway. Furthermore, the highest affinities were noted between four main compounds and six genes (FABP3-Propyleneglyco monoleate, FABP4-25-Oxo-27-norcholesterol, NR1H3-Campesterol, PPARA-β-sitosterol, PPARD-β-sitosterol, and PPARG-β-sitosterol)., Conclusion: Our study overall suggests that the four key compounds detected in SB might ameliorate T2DM severity by activating the PPAR signaling pathway., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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