Self-Assembled Nanoparticles from Xie-Bai-San Decoction: Isolation, Characterization and Enhancing Oral Bioavailability.

Background: Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral bioavailability of active compounds has not been elucidated. Using Xie-Bai-San decoction (XBSD) as an example, the purpose of this study was to isolate, characterize and elucidate the mechanism of the nanoparticles (N-XBSD) in XBSD, and further to explore whether the bioavailability of the main active compounds could be enhanced by N-XBSD. Methods: N-XBSD were isolated from XBSD, and investigated its characterization and study of its formation mechanism, and evaluation of its ability to enhance bioavailability of active compounds. Results: The N-XBSD was successfully isolated with the average particle size of 104.53 nm, PDI of 0.27 and zeta potential of -5.14 mV. Meanwhile, all the eight active compounds were most presented in N-XBSD. Kukoamine B could self-assemble with mulberroside A or liquiritin to form nanoparticles, respectively. And the FT-IR and HRMS results indicated the possible binding of the ammonium group of kukoamine B with the phenolic hydroxyl group of mulberroside A or liquiritin, respectively. The established UPLC-MS/MS method was accurate and reliable and met the quantitative requirements. The pharmacokinetic behaviors of the N-XBSD and decoction were similar in rats. Most notably, compared to that of free drugs, the Cmax, AUC0-∞, AUC0-t, T1/2 and MRT0-∞ values of index compounds were the higher in N-XBSD, with a slower plasma clearance rate in rats. Conclusion: The major active compounds of XBSD were mainly distributed in N-XBSD, and N-XBSD was formed through self-assembly among active compounds. N-XBSD could obviously promote the bioavailability of active compounds, indicating natural nanoparticles of decoctions play an important role in therapeutic effects.

Influences of carbon and nitrogen sources and metal ions on the heterotrophic culture of Scenedesmus sp. LX1.

In this study, the influences of organic carbon sources (OCS, including xylose, glucose, maltose, sucrose, and starch) and inorganic and organic nitrogen sources (INS, including ammonia chloride and sodium nitrate; ONS, including arginine, alanine, proline, and valine) and metal ions (including Na+, K+, Mn2+, Zn2+ and Cu2+) on the growth, lipid accumulation, and nitrogen and phosphorus (N&P) removal capabilities of oleaginous Scenedesmus sp. LX1 under heterotrophic conditions were investigated. The results showed that glucose was the only OCS for Scenedesmus sp. LX1 to grow well with specific growth rate of 0.935 days-1, maximum biomass of 1.72 g L-1, and largest removal rates of N&P and organic carbon reaching 72.228%, 93.034%, and 19.208%, respectively. After 11 days of cultivation, the maximal biomass reached in the group with starch or glucose while maximal lipid and triacylglycerol (TAG) yields reached in the groups with maltose and sucrose, respectively. Sodium nitrate was best nitrogen source as the largest algal density, maximal yields of lipids and TAGs, and highest N&P removal rates reached up to 1.105 × 107 cells·mL-1, 196.70 mg L-1, 5.19 mg L-1, 89.61% and 100%, respectively. Scenedesmus sp. LX1 was found to have great tolerance to Na+, K+, Mn2+, and Zn2+ while 0.5 mg L-1 Cu2+ had a strong inhibition on growth and N&P removal rate of Scenedesmus sp. LX1. Concentration increasing of five metal ions all caused the yield increases of microalgal lipid and TAGs. Graphical abstract.