New insight of chemical constituents in Persea americana fruit against obesity: A data-driven study
Ki‐Kwang Oh, Sang Jun Yoon, Su-Been Lee, Sangyoon Lee, Haripriya Gupta, Raja Ganesan, Satya Priya Sharma, Sung‐Min Won, Jin‐Ju Jeong, Dong Joon Kim, Ki Tae Suk · Research Square · 2023
Abstract BACKGROUND Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids. Unsaturated fatty acids are of significance in dietary supplementation, as they relieve metabolic disorders, including obesity (OB). Unquestionably, a plethora of natural plants contain fatty acids like those found in PAF. This study focused on the anti-OB efficacy of the non-fatty acids in PAF using a network pharmacology approach. METHODS The chemical constituents of PAF were retrieved from the NPASS database and literature sources. The OB-related targets obtained by DisGeNET and the overlapping targets from the SEA and STP databases were analyzed with a Venn diagram to discover the crucial targets in OB. The crucial targets were analyzed via PPI and PSTC networks, the constructed bubble chart and molecular docking studies. Finally, the toxicities of the key compounds were identified by ProTox-II. RESULTS A total of 41 chemical compounds in PAF were identified by NPASS and other reports. The 31 overlapping targets were selected from the 52 intersecting targets and OB-related targets (3028) and were considered to be key protein encoding genes in OB, with AKT1 being the most significant among them. On the bubble chart, the PPAR signaling pathway had the highest rich factor and its modulation was determined to be the key mechanism, suggesting that this pathway may have an agonistic function for the treatment of OB. Likewise, the PSTC network showed that AKT1 had the greatest degree value. The MDA results showed that AKT1-γ-tocopherol, PPARA-fucosterol, PPARD-stigmasterol, PPARG-fucosterol, NR1H3-campesterol, and ILK-α-tocopherol formed the most stable complexes. These five key compounds were nontoxic, and could be developed as new antagonists to alleviate OB. CONCLUSION In summary, alpha-tocopherol, gamma-tocopherol, fucosterol, stigmasterol, and campesterol might be key players in the activation of the PPAR signaling pathway.