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Many Selaginellaceae species are used as traditional medicines in Asia. This study is the first to investigate the anti-obesity and anti-diabetic effects of Selaginella rossii (SR) in high-fat diet (HFD)–fed C57BL/6J mice. Seven-day oral administration of ethanol extract (100 mg/kg/day) or ethyl acetate (EtOAc) extract (50 mg/kg/day) from SR improved oral fat tolerance by inhibiting intestinal lipid absorption; 10-week long-term administration of the EtOAc extract markedly reduced HFD-induced body weight gain and hyperglycemia by reducing adipocyte hypertrophy, glucose levels, HbA1c, and plasma insulin levels. Treatment with SR extracts reduced the expression of intestinal lipid absorption-related genes, including Cd36, fatty acid-binding protein 6, ATP-binding cassette subfamily G member 8, NPC1 like intracellular cholesterol transporter 1, and ATP-binding cassette subfamily A member 1. In addition, the EtOAc extract increased the expression of protein absorption–related solute carrier family genes, including Slc15a1, Slc8a2, and Slc6a9. SR extracts reduced HFD-induced hepatic steatosis by suppressing fatty acid transport to hepatocytes and hepatic lipid accumulation. Furthermore, amentoflavone (AMF), the primary compound in SR extracts, reduced intestinal lipid absorption by inhibiting fatty acid transport in HFD-fed mice. AMF-enriched SR extracts effectively protected against HFD-induced body weight gain and hyperglycemia by inhibiting intestinal lipid absorption.

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Amentoflavone-Enriched Selaginella rossii Warb. Suppresses Body Weight and Hyperglycemia by Inhibiting Intestinal Lipid Absorption in Mice Fed a High-Fat Diet