Integrated Computational Analysis of Phoenix dactylifera and Ficus carica Reveals Therapeutic Networks and Gut-Related Pathways Associated with Obesity and Gastrointestinal Disorders

Obesity and gastrointestinal (GI) disorders are complex conditions associated with metabolic dysregulation, chronic inflammation, impaired gut homeostasis, and progressive complications that may lead to disability. In this study, an integrated in silico approach was employed to identify potential multitarget therapeutic inhibitors using phytochemicals derived from Phoenix dactylifera (date palm) and Ficus carica , two plants widely cultivated in Saudi Arabia and recognized for their remarkable medicinal and health-promoting properties. Disease and compound-associated targets were systematically analyzed to identify key overlapping proteins involved in both disorders. A PPI network was constructed and hub genes were identified using integrated topological analysis (degree, betweenness, closeness, MCC, and MNC). Venn diagram integration of these parameters revealed nine key hub genes: AKT1, ALB, BCL2, EGFR, ESR1, IL6, PPARG, SRC, and TP53, which are critically involved in metabolic regulation, inflammatory signaling, apoptosis, and cellular homeostasis. Molecular docking revealed strong multitarget interactions of 1,3,6-tri-O-galloyl- β -D-glucose (TGG) with key proteins, particularly PPARG (−11.6 kcal/mol), AKT1 (−10.9 kcal/mol), and ALB (−9.6 kcal/mol), while 100 ns MD simulations confirmed stable complex formation through consistent RMSD (2.5–3.5 Å), stable Rg (17.8–18.3 Å), SASA, and persistent H bonding interactions. DFT analysis further demonstrated favorable electronic properties, including a HOMO–LUMO energy gap of 3.84 eV and electrophilicity index of 3.38 eV, supporting its stability, reactivity, and potential as a promising therapeutic candidate. Further experimental investigations are necessary to validate its activity against the identified targets and assess its therapeutic applicability.