Pomaces of sea buckthorn berry were usually side-products during the processing of juice. Due to a lack of an economical and effective extraction method, it was typically recognized as waste. For the purpose of resource utilization, the mechanochemical-assisted extraction (MCAE) method was applied to develop an ecofriendly extraction method and product with better pharmacology activity. The parameters were investigated through response surface methodology (RSM) design experiments. The processing conditions were optimized as follows: amount of Na₂CO₃ 40%, ball-to-material rate 29:1 g/g, milling speed 410 rpm, milling time 24 min, extraction temperature 25 °C, extraction time 20 min and the solid-to-solution ratio 1:10 g/mL. Under these conditions, the yields of flavonoids from sea buckthorn pomaces were 26.82 ± 0.53 mg/g, which corresponds to an increase of 2 times in comparison with that extracted by the heat reflux extraction method. Meanwhile, the hepatoprotective activity of sea buckthorn pomaces extracts was studied by the liver injury induced by ip injection of tetracycline. Biochemical and histopathological studies showed that biomarkers in serum and liver of nonalcoholic fatty liver disease (NAFLD) mice were significantly ameliorated when sea buckthorn flavonoids extracted by MCAE were used. Altogether, these results demonstrate that, as a green and efficient extraction, MCAE treatment could increase the extraction yield of sea buckthorn flavonoids, meanwhile it could exhibit significant activity of improving liver function. This research provided a new way to use pomaces of sea buckthorn as a functional food. It also has great value on the comprehensive utilization of nature’s resources.

This study aimed to develop a novel degrader capable of selectively degrading fibroblast growth factor receptor 2 (FGFR2) to overcome the issues of drug resistance and adverse reactions associated with traditional inhibitors in the treatment of FGFR2-driven tumors. Erdafitinib was employed as the targeting ligand, and its aliphatic amine site was conjugated with a CRBN E3 ligase ligand to design and synthesize a series of PROTAC molecules with different linkers. Screening was performed in KATO III cells with high FGFR2 expression, leading to the identification of LC-JD-6 as a potent degrader. Experimental results demonstrated that LC-JD-6 effectively induced FGFR2 protein degradation with a half-maximal degrading concentration (DC ₅₀ ) of 121.4 nM, and this effect exhibited time- and concentration-dependence. Assessed at the cellular level, LC-JD-6 has a half-maximal inhibitory concentration in the KATO III (IC ₅₀ ) of 96.0 nM and showed low inhibitory activity in normal cells. Selectivity analysis revealed that LC-JD-6 specifically degraded FGFR2 with minimal impact on other FGFR subtypes. Further studies confirmed that LC-JD-6 also efficiently reduced the expression of FGFR2 on the cell membrane surface. In conclusion, this study successfully developed LC-JD-6, a novel FGFR2-selective degrader, and for the first time confirmed its ability to degrade the membrane-bound form of FGFR2. This work provides an innovative targeted protein degradation strategy for the treatment of FGFR2-driven tumors and holds significant potential for clinical application.