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Pharmacological activities of some natural products diminish and even disappear after purification. In this study, we explored the mechanisms underlying the decrease of acute oral toxicity of  Coptidis Rhizoma  extract after purification. The water solubility,  in vitro  absorption, and plasma exposure of berberine (the major active compound) in the  Coptidis Rhizoma  extract were much better than those of pure berberine. Scanning electron microscopy, laser scanning confocal microscopy (LSCM), and dynamic light scattering experiments confirmed that nanoparticles attached to very fine precipitates existed in the aqueous extract solution. The LSCM experiment showed that the precipitates were absorbed with the particles by the mouse intestine. High-speed centrifugation of the extract could not remove the nanoparticles and did not influence plasma exposure or acute oral toxicity. However, after extract dilution, the attached precipitates vanished, although the nanoparticles were preserved, and there were no differences in the acute oral toxicity and plasma exposure between the extract and pure berberine. The nanoparticles were then purified and identified as proteinaceous. Furthermore, they could absorb co-dissolved berberine. Our results indicate that naturally occurring proteinaceous nanoparticles in  Coptidis Rhizoma  extract act as concentration-dependent carriers that facilitate berberine absorption. These findings should inspire related studies in other natural products.

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Naturally occurring proteinaceous nanoparticles in Coptidis Rhizoma extract act as concentration-dependent carriers that facilitate berberine absorption