Integrated Network Pharmacology, In Silico, and In Vitro Evaluation of Antioxidant Activity from the Methanol Extract of Salacca zalacca Skin
DOI:
https://doi.org/10.48048/tis.2026.11630Keywords:
Methanol extract of Salacca zalacca skin, Oxidative stress, Molecular docking, Molecular dynamics, Natural compound, ABTS, DPPHAbstract
Salacca zalacca (SZ) is an indigenous tropical fruit from Indonesia, rich in phytochemicals with notable antioxidant potential. However, the antioxidant mechanisms of the methanol extract from SZ skin remain unclear. This study evaluated the antioxidant properties of the methanol extracts from SZ skin using an integrated approach combining network pharmacology, in silico, and in vitro analyses. The methanol extract of SZ skin was analyzed using targeted liquid chromatography-mass spectrometry (LC-MS), while the pharmacokinetic properties were assessed using the pkCSM and PASS Online databases. Protein-protein interactions were explored using NCBI and GeneCards. Molecular docking and dynamic simulations were performed with PyRx v8.0, PyMol, and YASARA. Targeted LC-MS identified 8 bioactive compounds: caffeic acid (C1), chlorogenic acid (C2), rutin (C3), stigmasterol (C4), gallic acid (C5), ferulic acid (C6), quercetin (C7), and β-sitosterol (C8). Pharmacokinetic analysis demonstrated that C1, C6, and C7 complied with Lipinski's Rule of Five. Biological activity predictions revealed that C3 had the highest antioxidant potential (Pa = 0.923) and free radical scavenging ability (Pa = 0.988). Molecular docking confirmed the strong binding affinity of C3 with KEAP1 (−9.3 kcal/mol), supported by molecular dynamics simulations showing stable ligand-receptor interactions and minimal residue fluctuations (< 3 Å). In vitro antioxidant assays showed that the methanol extract of SZ skin had stronger ABTS radical scavenging activity (EC50 = 87.83 µg/mL) than Trolox (EC50 = 325.1 µg/mL), although its DPPH activity was lower (EC50 = 496.0 vs. 61.18 µg/mL for Trolox). Overall, these findings suggest that the methanol extract of SZ skin is a promising natural source of antioxidants. However, further studies are needed to clarify the antioxidant mechanism.
HIGHLIGHTS
- Targeted LC-MS identified 8 bioactive compounds in the methanol extract of Salacca zalacca skin, including rutin, caffeic acid, chlorogenic acid, gallic acid, stigmasterol, ferulic acid, β-sitosterol, and quercetin.
- Rutin exhibited the strongest binding affinity and stable interactions with KEAP1 proteins.
- The methanol extract of Salacca zalacca skin had higher ABTS radical scavenging activity compared to DPPH activity.
- The methanol extract of Salacca zalacca skin represents a promising natural source of antioxidants.
GRAPHICAL ABSTRACT
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