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

Hesperetin-7-O-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 in vitro and in vivo 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 in vivo 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 Tnf-α and IL-22. Furthermore, dietary Hes-7-G not only profoundly regulated the gut microbiota composition including phyla Bacteroidetes, Cyanobacteria, Desulfobacterota, and Deferribacteres and genus Enterorhabdus, Prevotellaceae, Gastranaerophilales, Enterococcus, Intestinimonas, Ruminococcaceae, and Eubacterium 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 in vitro and in vivo and potential preventive or therapeutic effects for chronic inflammation diseases.

anti-inflammation; hesperetin-7-O-glucoside; host metabolism; metabolites; microbiome.