<i>In Vitro</i> and <i>In Vivo</i> Studies Reveal that Hesperetin-7-<i>O</i>-glucoside, a Naturally Occurring Monoglucoside, Exhibits Strong Anti-inflammatory Capacity

Hesperetin-7-<i>O</i>-glucoside (Hes-7-G) is a naturally occurring flavonoid monoglucoside in Citri Reticulatae Pericarpium and exhibits relatively high biological activities. To explore the anti-inflammatory capacity of dietary Hes-7-G, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and dextran sodium sulfate (DSS)-induced colitis mice were used here as <i>in vitro</i> and <i>in vivo</i> inflammation models. The results showed that Hes-7-G (5 μM) significantly restored cellular metabolic disorders and inflammation in LPS-stimulated RAW264.7 macrophages. In the <i>in vivo</i> study, dietary Hes-7-G (1 mg/kg body weight) markedly alleviated the inflammatory status in DSS-induced colitis mice, manifested by the recovered colon length from 5.91 ± 0.66 to 6.45 ± 0.17 cm, histopathological changes, and mRNA levels of colonic inflammatory factors including <i>Tnf-α</i> and <i>Il-22</i>. Furthermore, dietary Hes-7-G not only profoundly regulated the gut microbiota composition including phyla Bacteroidetes, Cyanobacteria, Desulfobacterota, and Deferribacteres and genus <i>Enterorhabdus</i>, <i>Prevotellaceae</i>, <i>Gastranaerophilales</i>, <i>Enterococcus</i>, <i>Intestinimonas</i>, <i>Ruminococcaceae,</i> and <i>Eubacterium</i> in the cecal contents but also especially adjusted the co-metabolites such as short chain fatty acids and indole metabolites (indole-3-propionic, indole acetic acid), which were markedly altered by DSS treatment in mice. These findings demonstrated that Hes-7-G has strong anti-inflammatory activity <i>in vitro</i> and <i>in vivo</i> and potential preventive or therapeutic effects for chronic inflammation diseases.