A network pharmacology study to investigate bioactive compounds and signaling pathways of garlic ( Allium sativum L.) husk against type 2 diabetes mellitus

During garlic harvest, much husk has been generated, nearly all husk is discarded as unnecessary by-products. However, in Korean folk remedies, 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, compounds are constructed, 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. PRACTICAL APPLICATIONS: Allium sativum L. husk (ASLH) has been regarded as wastes that come from garlic (Allium sativum L.). During the harvesting period of garlic, a considerable amount of ASLH is a severe problem in farm communities. Particularly, garlic bioactive compounds are well documented including organosulfur compounds. Conversely, at present, no information is available on chemical compounds of ASLH to use in health industries. Taking this matter into consideration, our analysis approach was to select drug-like compounds (DLCs) from ASLH via GC-MS, thereby we can explore the compounds with high cell permeability. The screened compounds can be used as nutraceutical or medicinal or even cosmetical resources. In this study, we described the significant compounds via the network pharmacology concept to uncover the pharmaceutical mechanism(s) of ASLH against T2DM. Eventually, this work provides nutraceutical or medicinal value of ASLH and suggests that ASLH might be used as an upcycling resource to relieve T2DM.