| Summary: | Abstract Honey has been used as a nutrient, an ointment, and a medicine worldwide for many centuries. Modern research has demonstrated that honey has many medicinal properties, reflected in its anti‐microbial, anti‐oxidant, and anti‐inflammatory bioactivities. Honey is composed of sugars, water and a myriad of minor components, including minerals, vitamins, proteins and polyphenols. Here, we report a new bioactive component‒vesicle‐like nanoparticles‒in honey (H‐VLNs). These H‐VLNs are membrane‐bound nano‐scale particles that contain lipids, proteins and small‐sized RNAs. The presence of plant‐originated plasma transmembrane proteins and plasma membrane‐associated proteins suggests the potential vesicle‐like nature of these particles. H‐VLNs impede the formation and activation of the nucleotide‐binding domain and leucine‐rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, which is a crucial inflammatory signalling platform in the innate immune system. Intraperitoneal administration of H‐VLNs in mice alleviates inflammation and liver damage in the experimentally induced acute liver injury. miR‐4057 in H‐VLNs was identified in inhibiting NLRP3 inflammasome activation. Together, our studies have identified anti‐inflammatory VLNs as a new bioactive agent in honey.
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