Isolation and characterization of nanometre aggregates from a Bai-Hu-Tang decoction and their antipyretic effect

In China, a decoction is one of the most common clinical dosage forms. Nanometre aggregates (NAs), which often consist of circular or irregular nanoparticles, have been observed in previous research on decoctions. A Bai-Hu-Tang (BHT) decoction is an ancient clinical dosage form in China. The purpose of this work was to isolate and characterize NAs from BHT and to investigate their antipyretic effect. A BHT decoction was prepared by the traditional method. The mechanism and active components of the aggregates in BHT were investigated by high-speed centrifugation, transmission electron microscopy (TEM), and HPLC (high-performance liquid chromatography). In addition to the aggregation, therapeutic activities were evaluated through temperature measurements, enzyme-linked immunosorbent assays, cellular uptake measurements and fluorescence imaging. The majority of the NAs in BHT had diameters of 100 nm, and the spherical structures contained C, O, Mg, Al, Si, Ca, Zn et al. Antipyretic bioactive compounds, such as neomangiferin, mangiferin, glycyrrhizic acid and ammonium glycyrrhizinate, existed in the aggregates. In addition, the NAs in BHT had a better antipyretic effect than the other dispersion phases of BHT. In particular, the nanometre aggregates of Bai-Hu-Tang (N-BHT) were easily taken up by cells, and the fluorescein isothiocyanate (FITC) signals of NAs were more enriched in the lungs and brain than in other organs over time. These results revealed that the antipyretic effect was associated with the NAs in BHT. The discovery of NAs might present a new perspective for understanding BHT decoctions and even lead to the development of a new nanomedicine approach in traditional Chinese medicine (TCMs). Therefore, this topic deserves further study.