As a naturally occurring flavonoid, 7,8-dihydroxyflavone (7,8-DHF) exhibits protective effects in preventing neurodegeneration by activating the tropomyosin receptor kinase B (TrkB). However, whether 7,8-DHF influences the progression of chronic diseases through TrkB-independent mechanisms remains largely unclear. Here, we discovered that 7,8-DHF could protect cells from oxidative stress-induced cell death by acting as a previously unrecognized inhibitor of ferroptosis. Ferroptosis is a form of programmed cell death caused by uncontrolled peroxidized phospholipids. Although 7,8-DHF functions as a neuron protector by acting as a TrkB agonist, our data demonstrate that 7,8-DHF suppresses ferroptosis independently of activating TrkB signaling pathways. Indeed, as natural radical-trapping antioxidants, 7,8-DHF directly neutralizes peroxidized phospholipids to inhibit ferroptosis in a GSH/GPX4-independent manner. Since the low bioavailability of 7,8-DHF in vivo limits its clinical uses, we developed engineered 7,8-DHF nanoparticles (7,8-NPs) to enhance its absorption and utilization in a pharmacokinetic model. Consistent with previous studies, we confirmed that 7,8-NPs effectively reduce Alzheimer's disease pathology. Moreover, we found that 7,8-NPs could alleviate ulcerative colitis by reducing inflammation and ferroptotic stresses, suggesting the critical role of 7,8-DHF against ferroptosis in vivo. These observed effects on ferroptosis inhibition demonstrated that 7,8-DHF exhibits a molecular signature associated with improved colon health.

The study investigated the effects of ethanol precipitation on the polysaccharide components obtained from 3 different oak acorns. The variables factors were ethanol precipitation times (1× or 2×), tree species (Quercus variabilis, Quercus aliena, Quercus dentata) and raw materials (whole acorn fruit or kernels). Through detections of acorn polysaccharide concentrations from different species and components analyses, we found that the second ethanol precipitation had a better extraction effect, and acorn polysaccharides were proved to be mainly composed of glucose, galacturonic acid, arabinose and galactose. Compared with other groups, the highest content of polysaccharides was proved to be extracted from Q. variabilis kernels, thus, acorn kernels should be suggested as the proper material for the extraction of acorn polysaccharides. Interestingly, acorn polysaccharides functionally alleviated liver and kidney damages in type 2 diabetes mice, they also had noticeable hypoglycemic effects and regulated insulin secretion, particularly in combination with metformin and D-mannuronic acid.