Kaempferia galanga L.-derived nanovesicles for protection against acute inflammation via the NF-κB signaling pathway.

Although the molecular mechanisms underlying excessive acute inflammatory responses have been widely studied, safe and effective therapeutic strategies remain limited. Herein, we investigated the protective effects of Kaempferia galanga L.-derived nanovesicles (KGNVs) against acute inflammatory injury and explored their underlying mechanisms. Lipidomic analysis revealed that KGNVs were enriched in lipids with reported anti-inflammatory and antioxidant potential, including unsaturated cardiolipins, ceramides, and monogalactosyldiacylglycerols. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, KGNVs significantly decreased the production of NO and pro-inflammatory cytokines, while increasing the levels of the anti-inflammatory cytokine and the antioxidant enzymes. These effects helped interrupt the amplification cycle between inflammation and oxidative stress. KGNVs also reduced mitochondrial oxidative stress, alleviated JC-1 depolarisation, suppressed caspase-3 activation, and attenuated excessive macrophage apoptosis. Mechanistically, these protective effects were associated with the inhibition of the NF-κB/p65-mediated inflammatory signaling pathway. In an LPS-induced zebrafish embryo inflammatory model, KGNVs alleviated reactive oxygen species accumulation, apoptosis, and excessive recruitment of neutrophils and macrophages in vivo. Transcriptomic analysis further confirmed the regulatory effects of KGNVs on inflammation- and oxidative stress-related genes. Collectively, these findings demonstrate that KGNVs alleviate LPS-induced acute inflammatory injury by suppressing NF-κB/p65-associated inflammatory activation, oxidative stress, mitochondrial dysfunction, and caspase-3-dependent apoptosis. These results highlight the potential of KGNVs as a natural nanotherapeutic platform for the treatment of acute inflammatory injury.