RESUMO
BACKGROUND: Scutellaria baicalensis Georgi is a well-known herb in traditional Chinese medicine that is frequently prescribed for various gastrointestinal conditions, including ulcerative colitis (UC). Its primary active constituent, baicalin, has poorly water solubility that reduces its efficacy. PURPOSE: To enhance the aqueous solubility of baicalin by optimising its extraction process. We compared the modulatory effects of isolated water-soluble baicalin and water-insoluble baicalin on UC, and delved deeper into the potential mechanisms of water-soluble baicalin. METHODS: We successfully extracted a more hydrophilic baicalin directly from an aqueous S. baicalensis Georgi extract through the process of recrystallisation following alcoholic precipitation of the aqueous extract obtained from S. baicalensis Georgi, eliminating the need for acid additives. This specific form of baicalin was conclusively identified by UV, IR, atomic absorption spectroscopy, elemental analysis, 1H NMR, 13C NMR, and ESI-HRMS. We subsequently compared the regulatory effects of baicalin on UC before and after optimisation, employing 16S rDNA sequencing, bile acid-targeted metabolomics, and transcriptome analysis to elucidate the potential mechanism of water-soluble baicalin; and the key genes and proteins implicated in this mechanism were verified through RT-PCR and western blotting. RESULTS: A new form of baicalin present in the aqueous solution of S. baicalensis Georgi was isolated, and its structural characterisation showed that it was bound to magnesium ions (baicalin magnesium) and exhibited favorable water solubility. Baicalin magnesium offers enhanced therapeutic benefits over baicalin for UC treatment, which alleviated the inflammatory response and oxidative stress levels while improving intestinal mucosal damage. Further investigation of the mechanism revealed that baicalin magnesium could effectively regulate bile acid metabolism and maintain intestinal microecological balance in UC mice, and suppress the activation of the nuclear factor-kappa B and peroxisome proliferator-activated receptor α signalling pathways, thereby playing a therapeutic role. CONCLUSIONS: Baicalin magnesium has good water solubility, which solves the bottleneck problem of water insolubility in the practical applications of baicalin. Moreover, baicalin magnesium exhibits therapeutic potential for UC significantly better than baicalin.
