Investigating the separation and purification of flavonoids extracted from foxtail millet, with an in‐depth study on its functions in alleviating metabolic syndrome through suppressing lipid absorption

Abstract BACKGROUND Rising living standards alongside high‐fat diets (HFDs) have fueled the prevalence of metabolic syndrome (MetS), posing a significant health challenge with limited effective therapies. Foxtail millet is recognized as a health food with rich flavonoids. The objective of this work is to isolate and purify flavonoids from foxtail millet, which have the potential to alleviate MetS and to clarify their mechanism. RESULTS Our research combined single‐factor experiments and a Box–Behnken design to optimize the extraction processes for millet whole‐grain flavonoids (MWGFs) followed by the purification using D101 resin. Components were eluted using varied alcohol concentrations. Additionally, the investigation revealed that MWGF30 notably decreased triglyceride (TG) levels, mitigated lipid uptake in Caco‐2 cells induced by free fatty acids, and suppressed lipid absorption in HFD mice while modulating TG, high‑ and low‐density lipoprotein cholesterol and total cholesterol levels. Further investigation uncovered that MWGF30 achieved this lipid uptake reduction ability by downregulating the CD36 protein level. CONCLUSION Collectively, MWGF30 demonstrated a potent ability to regulate blood lipids and curb lipid absorption, enhancing our comprehension of millet's benefits and furnishing a scientifically grounded dietary approach for MetS. © 2025 Society of Chemical Industry.