Cationic fructan-based pH and intestinal flora dual stimulation nanoparticle with berberine for targeted therapy of IBD.

Inflammatory bowel disease (IBD) can cause intestinal microbial imbalance and aggravate intestinal inflammation. Mixed fructan is more easily fermented by colonic microorganisms and can be used as colonic drug delivery materials. Here, we constructed a mixed fructan based nanoparticle with dual targeted stimulation of pH and intestinal flora to effectively deliver berberine for the treatment of ulcerative colitis (UC). The complex of fructan based nanoparticle and berberine (BBRNPs) significantly ameliorated the inflammatory response of sodium dextran sulfate (DSS)-induced colitis in mice by inhibiting the activation of NF-κB/STAT-3 pathway and increasing tight junction protein expression in vivo. Importantly, BBRNPs improved the responsiveness of colitis microbiome and effectively regulated the relative homeostasis of harmful flora Enterobacteriaceae and Escherichia-shigolla, and beneficial flora Ruminococcaceae and Akkermansiaceae. This study provides a promising strategy for the effective treatment of UC and expands the application of branched fructan in pharmaceutics.

Comparative chemical characters of Pseudostellaria heterophylla from geographical origins of China.

Objective: Pseudostellaria heterophylla has been paid more attention in recent years, mainly as a medicine food homology plant. The content determination of P. heterophylla is not specified in the Chinese Pharmacopoeia (version 2020). The environmental conditions in different production areas could exert an influence on the quality of P. heterophylla. The purpose of this study is to discriminate P. heterophylla collected from different geographical origins of China. Methods: In this study, the content of polysaccharide in 28 batches of P. heterophylla was determined using phenol-sulfuric acid. HPLC fingerprints were established under optimised HPLC-PDA methods. Subsequently, the similarity analysis (SA) and the quantification of heterophyllin B were analyzed. The metabolites of P. heterophylla were identified and evaluated using UHPLC-Q Exactive HF orbitrap MS system. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and orthogonal PLS-DA (OPLS-DA) were performed based on all peak areas. Results: The polysaccharide content in Guizhou and Jiangsu was higher than that of other production areas, which varied significant from different origins. While the content of heterophyllin B in Anhui and Jiangsu was high. The correlation coefficients of HPLC fingerprints for 28 batches samples ranged from 0.877 to 0.990, and the characteristic map can be used to identify and evaluate the quality of P. heterophylla. The samples from Fujian, Guizhou, Jiangsu provinces can be relatively separated using multivariate statistical analysis including PCA, PLS-DA, HCA, OPLS-DA, indicating that their metabolic compositions were significantly different. Ultimately, a total of 15 metabolites which were filtrated by a VIP-value > 1 and a P-value < 0.05 associated with the separation of different origins were identified. Conclusion: HPLC fingerprint was established to evaluate the quality and authenticity of P. heterophylla. The present work showed that the difference of geographic distributions had an influence on the internal chemical compositions. A sensitive and rapid untargeted metabolomics approach by UHPLC-Q Exactive HF orbitrap MS was utilized to evaluate P. heterophylla from different origins in China for the first time. Overall, this study provides insights to metabolomics of P. heterophylla and supplies important reference values for the development of functional foods.