Uncovering of bioactives and mechanisms of garlic (Allium sativum L.) husk for the amelioration of type 2 diabetes mellitus via network pharmacology

Allium sativum L. husk (ASLH) extracts have been used as a reliever against type 2 diabetes mellitus (T2DM). Currently, its significant mechanisms against T2DM remain unclear. Thus, the aim of this study is to investigate the characteristics of its key signaling pathways, targets, and compounds. The compounds in ASLH were analyzed by gas chromatography-mass spectrum (GC–MS) and confirmed drug-like compounds (DLCs) in silico. Then, protein-protein interaction (PPI) networks and signaling pathways, targets, and compounds are constructed, and visualized by using RStudio. Finally, we performed a molecular docking test (MDT) to identify the key mechanism(s), target(s), and compound(s) of ASLH on T2DM. A total of 23 compounds in ASLH were identified by GC–MS, and all compounds were accepted by Lipinski’s rule. The 23 compounds were associated with 521 targets and retrieved 4,736 T2DM-related targets by Online Mendelian Inheritance in Man (OMIM) and DisGeNET. The final overlapping 87 targets were obtained between compounds–targets and T2DM-related targets. The number of 13 signaling pathways, 33 targets, and 19 compounds of ASLH were associated with T2DM. In parallel, MDT revealed four potential compounds: (1) 9-hexacosene, (2) 2-(([2-ethylhexyl]oxy)carbonyl)benzoic acid, (3) clionasterol, (4) 4-methyl-2-phenylpyrimidine on PPAR signaling pathway. Overall, the four compounds from ASLH might show an anti-T2DM synergistic effect by activating the PPAR signaling pathway or inactivating the phospholipase D signaling pathway. In this study, we suggest that ASLH might be considered a health-promising resource from both nutraceutical and pharmaceutical perspectives.