Diana Yuswanti Putri, Yuyun Yueniwati, Sri Utami, Mokhamad Fahmi Rizki Syaban, Nirmala Halid, Purnawan Pontana Putra, Sastia Prama Putri, Husnul Khotimah
Metabolic syndrome (MetS) remains a health concern condition characterized by hyperglycemia, obesity, and hypertension, requiring effective interventions such as antioxidant support and inhibition of digestive enzymes. Salacca zalacca skin (SZS), traditionally used for its antioxidant, anti-inflammatory, and lipid-lowering properties, shows promise in addressing MetS, though its molecular mechanisms remain underexplored. This study evaluated the potential of ethanol extract of SZS in managing MetS through in vitro and in silico approaches. LC-MS/MS analysis identified 16 bioactive compounds. Network pharmacology and molecular docking revealed that diphyllin, 19-norandosterone, and anastrozole exhibited strong and stable binding affinities to MetS-related targets: TNF-α (−6.7, –6.6, and –6.1 kcal/mol) and PPARG (−7.4, –7.1, and –7.9 kcal/mol), supported by molecular dynamics simulations. Antioxidant assays demonstrated moderate activity, with EC₅₀ values of 776.4 µg/mL (ABTS) and 647.8 µg/mL (DPPH). SZS inhibited lipase (EC₅₀ = 4,330 µg/mL) and α-glucosidase (EC₅₀ = 481.1 µg/mL), indicating its potential to regulate lipid and glucose metabolism. These findings suggest that SZS may exert multi-targeted effects by scavenging free radicals, inhibiting digestive enzymes, and modulating inflammatory and metabolic pathways. This study is the 1st to integrate in vitro and in silico evidence for SZS in MetS management, laying the groundwork for its development as a nutraceutical. Future research should focus on formulation refinement, compound synergy, and long-term clinical validation. © 2025, Walailak University. All rights reserved.
Program in Medical Sciences, Faculty of Medicine, Universitas Brawijaya, East Java, 65145, Indonesia; Department of Radiology, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar General Hospital, East Java, 65111, Indonesia; Faculty of Medicine, Universitas Brawijaya, East Java, 65145, Indonesia; Master Program in Biomedical Science, Faculty of Medicine Universitas Brawijaya, East Java, 65145, Indonesia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Andalas, Padang, 25163, Indonesia; Department of Biotechnology, The University of Osaka, Osaka, 565-0871, Japan
