Influence of drying temperature on the metabolites profile and potential antioxidant pathways of Passiflora edulis peel: Integrating untargeted metabolomics with network pharmacology analyses, molecular docking, and molecular dynamics simulation

Passiflora edulis peels consist of considerable antioxidative potential, which attributed to their diverse bioactive components. Nevertheless, these substances are susceptible to thermal degradation which can diminish their usefulness, resulting in resource wastage. This current research explore the influence of drying under varying temperature conditions (room temperature (∼28 °C), 40°C, and 70°C) on the antioxidant properties and metabolite composition of P. edulis peel extracts. A comprehensive analytical approach was adopted, encompassing proximate analysis, vitamin C quantification, total phenolic and flavonoid determinations, free radical scavenging assays, metabolite profiling, network pharmacology, molecular docking, and molecular dynamics simulation. In this study, the content of crude fibre and primary metabolites including fat, protein and carbohydrate were shown to be affected by the elevating drying temperature. Likewise, extract of P. edulis peels dried at room temperature established significant antioxidant activity at 1 mg/mL, inhibiting 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) by 81.20 % and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS⁺•) by 83.52 %. The content of secondary metabolites such as phenolics and flavonoids was also shown to be affected by temperature, which peels dried at room temperature harbour substantial phenolics and flavonoids content values, 23.71 ± 3.86 mg GAE/g and 35.43 ± 0.10 mg QE/g. The results from metabolite profiling analysis via LC-MS QTOF discovered that the room temperature extract contains 18 potential compounds, including oleamide, 6E,9E-octadecadienoic acid, C16 sphinganine, dodecanamide, and 2-hexyl-decanoic acid. Swiss Target Prediction was employed to identify hypothetical molecular targets, while oxidative stress-related targets were retrieved from the DrugBank, GeneCards, and DisGENET databases. A component–target-pathway network was constructed, encompassing 12 bioactive compounds after initial ADMET screening and 10 hub genes namely TP53, AKT1, CASP3, BCL2, STAT3, HSP90AA1, HSP90AB1, BCL2L1, ESR1, and MDM2. The identified potential antioxidant-related pathways included intrinsic apoptotic signalling, mitochondrial membrane organisation, and mitochondrial transport, among others. Structure-based virtual screening through molecular docking revealed that (S)-2-Hydroxy-2-phenylacetonitrile O-b-D-allopyranoside exhibited significant interaction with HSP90AB1, resulting in a binding affinity of −8.4 kcal/mol. These findings reinforce the pharmacological relevance of P. edulis peels as a high-value reservoir of potential antioxidant substances suitable for the development of functional foods and drugs for disease prevention and health promotion.