Ultrasound-assisted extraction of hypolipidemic actives from lotus (Nelumbo nucifera Gaertn.) seedpod: Process optimization, phytochemical characterization, and hypolipidemic activity

Lotus seedpod is a by-product of Lotus seed planting industry with abundant polyphenols. This study optimized the ultrasonic-assisted extraction (UAE) parameters of hypolipidemic compounds from lotus seedpod by response surface methodology guided-by lipase inhibition activity (LPIA). The major active compounds were enriched and identified, the in vitro and in vivo lipid lowering effect was explored by cell and mice models. The optimized conditions were 69% ethanol aqueous solution, ultrasonic power of 300 W and time of 62 min, under which the total polyphenol (TPC) and total flavonoid content (TFC) reached 125.41 mg GAE/g DM and 361.82 ± 2.76 mg QUE/g DM, respectively, with pancreatic lipase inhibitory activity (PLIA) of 8.38 ± 0.20 mg DM/mL. Ethyl acetate was the suitable solvent for enriching the hypolipidemic fraction in lotus seedpod polyphenol extract (LSPE). LSPE exhibited promising lipase inhibition (IC₅₀ value = 171.5 μg/mL) and significantly decreased the lipid accumulation in 3 T3-L1 cells. Flavonoids, especially for quercetin and kaempferol derivatives, were the major compounds. In vivo assays indicated that LSPE treatment reduced weight gain and serum lipid level, and repaired liver damage by alleviating oxidative stress and inflammation in obese mice. These findings highlight the potential of lotus seedpod as a natural source of hypolipidemic actives, while also demonstrating the high efficiency of UAE in extracting plant-based hypolipidemic compounds.