Plant-derived exosome-like nanoparticles (ELNs) exhibit diverse physiological activities across biological kingdoms. Talinum fruticosum (L.) Juss., known in Okinawa as 'Shibiran', is a traditional edible medicinal plant that is considered a food-based remedy. Okinawa, one of the five globally recognized 'blue zones', is renowned for its longevity and distinctive health practices. In Okinawan culture, the boundary between food and medicine is often blurred, and medicinal plants such as T. fruticosum are regularly incorporated into the daily diet for their health-promoting properties. However, the biological basis of the health benefits remains poorly understood. To assess its potential pharmacological value, ELNs from T. fruticosum (TfELNs) were isolated and characterized, and their key biological activities were examined. TfELNs were isolated from fresh leaves via ultracentrifugation followed by sucrose density gradient centrifugation. Their size and morphology were analyzed using nanoparticle tracking analysis and transmission electron microscopy. Subsequently, anti-inflammatory effects were evaluated in human THP-1 macrophages stimulated with lipopolysaccharide (LPS) using a multiplex cytokine immunoassay. Antioxidant activity was assessed in THP-1 macrophages under hydrogen peroxide-induced oxidative stress, with intracellular reactive oxygen species (ROS) levels measured using a DCFH-DA fluorescence assay. TfELNs were identified as spherical vesicles with typical exosome-like features, and they exhibited no notable cytotoxicity, thus indicating high biocompatibility. Notably, distinct subset-specific bioactivities were observed: The B2 fraction significantly suppressed LPS-induced interleukin-6 (IL-6) production in THP-1 macrophages, whereas the B1 fraction markedly reduced ROS levels under oxidative stress. These results suggested that TfELNs may exert selective anti-inflammatory and antioxidant activities, highlighting their potential utility in managing IL-6-associated inflammatory and oxidative stress-related conditions. These subset-specific activities suggest a unique pharmacological profile of TfELNs that could inspire future therapeutic applications. Furthermore, these findings may partially explain the traditional medicinal value attributed to T. fruticosum and underscore its relevance in the ethnopharmacological context of Okinawan healthy longevity.
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