Raymond Rubianto Tjandrawinata, Astri Arnamalia, Hendy Dwi Warmiko, Happy Kurnia Permatasari, Nurpudji Astuti Taslim, Hardinsyah Hardinsyah, Fahrul Nurkolis
Indonesia’s spices have a longstanding history in traditional medicine, yet comprehensive scientific validation remains limited. This study represents the first integrative effort combining metabolomics, chemometrics, in silico, and in vitro analyses to systematically elucidate the bioactive landscape and multifunctional properties of Indonesian spices. Five prominent spices—black pepper, nutmeg, cinnamon, clove, and ginger—were analyzed to bridge traditional knowledge with modern scientific validation. Metabolomic profiling utilized UHPLC-HRMS, followed by chemometric analysis (PCA, PLS-DA). Computational in silico analyses, including molecular docking and network pharmacology, identified potential biological targets. Functional activities were validated via in vitro assays: antioxidant (ABTS, DPPH), anticancer (MTT assay), anti-aging (tyrosinase, elastase inhibition), and anti-obesity (HMGCR inhibition). Metabolomic analysis identified key phytochemicals, including piperine in black pepper (14.30%), cinnamaldehyde in cinnamon (20.44%), and shogaol in ginger (5.29%). Chemometric clustering significantly validated distinct spice profiles (PCA variance explained: PC1 = 30.1%, PC2 = 26.9%). Molecular docking analysis showed robust affinities for compounds such as biflorin from clove to HMGCR (-10.7 kcal/mol), and pyrrolidinedione from black pepper to COX-2 (-12.2 kcal/mol). In vitro assays confirmed potent antioxidant activities in ginger and black pepper (IC₅₀ < 50.0 µg/mL in DPPH and ABTS), strong anti-aging effects in cinnamon (tyrosinase IC₅₀ = 14.6 µg/mL) and ginger (elastase IC₅₀ = 89.7 µg/mL), notable anticancer effects for black pepper (IC₅₀ = 190–300 µg/mL), and significant HMGCR inhibition for black pepper and ginger (low IC₅₀ values). This integrative study scientifically validates traditional claims about Indonesian spices, identifying critical bioactive compounds and mechanisms underpinning their health benefits. The findings highlight their potential as functional ingredients or nutraceuticals for antioxidant, anticancer, anti-aging, and anti-obesity applications. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
Center for Pharmaceutical and Nutraceutical Research and Policy, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia; Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Industri Selatan V PP-7, Jababeka 2, Cikarang, 17550, Indonesia; Department of Chemistry, Faculty of Science and Technology, IPB University, Bogor, 16680, Indonesia; Corpora Science Research Laboratory, Yogyakarta, 55223, Indonesia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia; Department of Community Nutrition, Faculty of Human Ecology, IPB University, Bogor, 16680, Indonesia; State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia; Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Medical Research Center of Indonesia, Surabaya, Indonesia
