Plant-derived extracellular vesicle-like nanoparticles (PDVLNs) have garnered significant attention in nanomedicine due to their low immunogenicity, excellent biocompatibility, and potential as drug delivery vehicles. However, conventional wisdom holds that these lipid membrane structures are sensitive to high temperatures and may disintegrate under prolonged heating. As a result, mainstream research has largely focused on extracting PDVLNs from fresh plant juices.
Recently, a revolutionary study has reshaped this understanding. By simulating the traditional decoction process, researchers successfully isolated structurally intact GGD-PDVLNs from dried Pueraria lobata after boiling. Surprisingly, these nanoparticles—having withstood exposure to 100 °C boiling water—not only retained their “cup-shaped” lipid bilayer structure but also demonstrated remarkable stability in simulated gastric acid and intestinal fluids, ensuring their ability to reach intestinal lesions intact.
Further research has unveiled the pivotal role of GGD-PDVLNs. In a mouse model of ulcerative colitis, the therapeutic effect of the GeGen decoction was almost completely lost when GGD-PDVLNs were removed. In contrast, administering the isolated GGD-PDVLNs alone fully replicated the therapeutic benefits of the whole GeGen decoction, providing compelling evidence that they are the core active ingredients responsible for GeGen decoction’s efficacy.
Further mechanistic investigation revealed that GGD-PDVLNs exert their effects through a microbiota-dependent pathway. They are actively taken up by intestinal bacteria, significantly increasing the abundance of beneficial strains such as Akkermansia and Bifidobacterium, thereby restoring a healthy gut microecological environment. This, in turn, suppresses intestinal inflammatory responses and repairs the damaged mucosal barrier. Using pseudo-germ-free mouse models, researchers confirmed that complete deletion of the gut microbiota abolished the therapeutic effects of GGD-PDVLNs.
This work represents not only a methodological breakthrough but also carries profound implications for TCM research and pharmaceutical development. It transforms the perception of herbal decoctions from simple “chemical soups” to “natural nano-drug delivery systems”, uncovering nanotechnological principles inherent in traditional preparation methods. Mechanistically, the study provides the first systematic elucidation of a complete and novel pathway—the “TCM nanoparticle–gut microbiota–immune barrier” axis—providing a nanoscale scientific foundation for interpreting the “multi-component, multi-target” mechanisms of TCM. Translationally, this discovery introduces a class of naturally derived, orally effective, and precisely targeted nanomedicine candidates for treating diseases such as inflammatory bowel disease, combining efficacy, safety, and cost-effectiveness.
The work titled “Vesicle-like nanoparticles extracted from Pueraria lobata decoction alleviate colitis by modulating the intestinal microbiota” was published in Extracellular Vesicles and Circulating Nucleic Acids (published on Feb. 12, 2026).
DOI：10.20517/evcna.2025.134