Abstract
Syzygium nervosum A. Cunn. ex DC., a plant traditionally used in Southeast Asian medicine, has recently gained scientific attention for its broad range of biological activities and health benefits, including anti-inflammatory, antimicrobial, and antitumor effects. In this study, we aim to compare the phytochemical composition, antioxidant capacity, and immunomodulatory effects of aqueous (SNPA) and ethanolic (SNPE) fruit pulp extracts in human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. Phytochemical quantification revealed that SNPE contained higher levels of phenolics, flavonoids, proanthocyanidins, and anthocyanins than SNPA, a finding further supported by LC–QTOF–MS profiling, which identified 20 compounds in SNPE compared with 6 compounds in SNPA, indicating ethanol’s superior extraction of polyphenolic constituents. Antioxidant assays (DPPH, ABTS, FRAP) demonstrated significantly stronger radical-scavenging and reducing activities in SNPE, correlating with its richer phytochemical profile. Both extracts were non-toxic to PBMCs and enhanced Th1-type immune responses, as indicated by increased levels of IL-2, TNF-α, and IFN-γ. Notably, SNPA triggered robust innate immune activation, markedly elevating IL-1β, IL-6, and TNF-β, whereas SNPE selectively upregulated IL-6 and strongly enhanced IL-10 production, highlighting differential immunomodulatory profiles. Collectively, these findings demonstrate that S. nervosum fruit pulp extracts, particularly SNPE, are rich in bioactive compounds with potent antioxidant and immunoregulatory activities, underscoring their promise as novel candidates for nutraceutical or therapeutic development targeting oxidative stress and immune regulation.