Rehmannia glutinosa Extracts Enhances Ketone Bodies Expression and Alleviates Ulcerative Colitis as A Novel Ketogenic...

The ketogenic diet (KD), as a clinically common method to increase ketone bodies, can induce adverse reactions due to alterations in normal dietary structure. This study aims to elucidate that Rehmannia glutinosa (DH), a representative plant among the "medicinal and edible homologous traditional Chinese medicines", also exhibits ketogenic effects and can be utilized to alleviate ulcerative colitis (UC). The ketogenic effects of DH were confirmed through molecular docking, enzyme activity assays, energy metabolism indicators, and ketone levels measurements. The safety profiles of DH were evaluated through hepatic and renal function indicator tests. The effects of DH and the traditional KD on UC were validated and compared via a dextran sulfate sodium-induced C57BL/6J mouse model and the measurement of pathological indicators related to UC. Animal studies demonstrated that administering DH extracts at a dose of 1.5 g/kg/day effectively enhanced ketone bodies expression in mice. This effect might be attributed to the increased activity of key enzymes involved in ketogenesis, such as 3-hydroxybutyrate dehydrogenase 1 and 3-hydroxymethylglutaryl-CoA synthase 2. In the UC model, both DH and KD significantly alleviated intestinal inflammation, oxidative stress injury, and mitigated UC damage. The primary mechanism might be related to the suppression of the STAT3 pathway. This study demonstrates that DH can serve as a novel ketogenic functional food to enhance ketone bodies expression and be applied for UC management.