Plant-Derived Nanovesicles for Ischemic Stroke Therapy via the Gut Microbiota-Gut-Brain Axis: A New Paradigm of...

Ischemic stroke (IS) is a globally significant disease with complex pathological mechanisms. Traditional therapeutic strategies centered on central nervous system-targeted delivery face substantial limitations due to the presence of the blood-brain barrier (BBB) and the multifactorial nature of the disease. In recent years, the gut microbiota-gut-brain axis, which elucidates the multi-pathway dialogue between the gut and the brain, has provided a novel systemic intervention perspective for IS treatment. In this context, Plant-Derived Nanovesicles (PDNVs), a class of natural nanocarriers derived from plants, have emerged prominently due to their inherent multi-component synergistic properties, excellent biocompatibility, and cross-kingdom regulatory capabilities. Critically, IS itself rapidly induces gut dysbiosis and barrier disruption, creating a vicious cycle that amplifies neuroinflammation-a pathological feature shared with other inflammatory conditions such as colitis and Inflammatory bowel disease. In this context, PDNVs, a class of natural nanocarriers derived from plants, have emerged prominently due to their inherent multi-component synergistic properties, excellent biocompatibility, and cross-kingdom regulatory capabilities. Drawing on mechanistic insights from these related disease models, this article systematically discusses the multi-level integrated mechanism of PDNVs as novel "functional messengers", involving reshaping the gut microenvironment, mediating systemic metabolic-immune signals, and ultimately synergistically activating the central nervous repair network, thereby offering a new paradigm for IS therapy. This review not only summarizes the mechanisms of action of PDNVs but also systematically constructs a framework and strategy for their translation from experimental research to clinical application. Highlighting critical hurdles such as the need for standardized production and rigorous quality control to ensure batch-to-batch consistency.