Design, synthesis and evaluation of a myricetin and nobiletin hybrid compound for alleviating hyperuricemia based on metabolomics and gut microbiota

Hyperuricemia (HUA) is the fourth most common basic metabolic disease that can cause damage to multiple organs throughout the body. In this study, a hybrid compound consisting of myricetin and nobiletin was synthesized and its biological activity was evaluated. We named the hybrid compound MNH, and its structure was confirmed by spectroscopy. This study used serum metabolomics profiling with LC/MS and 16S rRNA gene sequencing analysis to explore the anti-HUA efficacy of MNH on a yeast paste-induced mouse model. The results showed that serum uric acid (UA), creatinine (CRE) and urea nitrogen (BUN) levels were significantly decreased after the intervention of MNH. The efficacy of MNH in lowering UA was somewhat greater than that of myricetin and nobiletin. In addition, MNH could repair the renal histopathological damage. Moreover, serum metabolomics demonstrated that MNH regulated the metabolic pathways involved in glycerophospholipid metabolism, arachidonic acid metabolism and alanine etc. Furthermore, MNH supplementation restored the composition of gut microbiota with remarkable reductions in Lactobacillus and Limosilactobacillus and significant elevations in norank_f_Muribaculaceae and Bacteroides at the genus level. Taken together, these results indicated that MNH might represent a protective effect against HUA via modulating gut microbiota and metabolomics.