Accumulating evidence have indicated that ferroptosis plays a crucial role in cerebral ischemia-reperfusion (I/R) injury which is the most serious treatment complication of ischemic stroke. Baicalein (5,6,7-trihydroxyflavone) is a main bioactive ingredient isolated from a traditional Chinese medicine named Baikal Skullcap, which is the root of Scutellaria baicalensis Georgi. This study investigated the potential role of baicalein in cerebral I/R injury using oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells, transient middle cerebral artery occlusion (tMCAO) mice and RSL3-sitmulated HT22 cells. Baicalein improved the viability of OGD/R cells and significantly ameliorated cerebral I/R injury in tMCAO mice. Baicalein decreased the iron levels, lipid peroxidation production and morphology features of ferroptosis of the brain tissues in tMCAO mice, which indicated that baicalein ameliorated cerebral I/R injury by inhibiting ferroptosis in vivo and in vitro. We further confirmed that baicalein had the activity of inhibiting ferroptosis in RSL3-stimulated HT22 cells. Western blot revealed that baicalein inhibited the ferroptosis by regulating on the expression levels of GPX4, ACSL4 and ACSL3 in OGD/R cells, tMCAO mice and RSL3-stimulated HT22 cells. Our findings demonstrated that baicalein reversed the cerebral I/R injury via anti-ferroptosis, which was regulated by GPX4/ACSL4/ACSL3 axis. The results suggested that baicalein has therapeutic potential as a drug for cerebral I/R injury.

Polysaccharides are one of many bioactive compounds found in edible mushrooms. Edible mushrooms have become attractive as “health foods” and as source materials for immunomodulators. The aim of this project was to study the immunoregulatory effects of a purified polysaccharide derived from wild Russula griseocarnosa (PRG1-1) on macrophages. Our data showed that in RAW264.7 macrophage cells, PRG1-1 increased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, PRG1-1 increased the production of nitric oxide (NO) and cytokines, including interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α). Western blotting demonstrated that the regulation of NO and cytokines was mediated through the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways. Therefore, PRG1-1 has the capacity to activate macrophages via the NF-κB and MAPK pathways. These findings helped to elucidate the immune-modulatory properties of the polysaccharide from R. griseocarnosa.

Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, and delicious taste, which are closely related to their rich active components. To date, many bioactive substances have been identified and purified from mushrooms, including proteins, carbohydrates, phenols, and vitamins. More importantly, molecules derived from mushrooms show great potential to alleviate the pathological manifestations of Alzheimer’s disease (AD), which seriously affects the health of elderly people. Compared with current therapeutic strategies aimed at symptomatic improvement, it is particularly important to identify natural products from resource-rich mushrooms that can modify the progression of AD. This review summarizes recent investigations of multiple constituents (carbohydrates, peptides, phenols, etc.) isolated from mushrooms to combat AD. In addition, the underlying molecular mechanisms of mushroom metabolites against AD are discussed. The various mechanisms involved in the antiAD activities of mushroom metabolites include antioxidant and anti-neuroinflammatory effects, apoptosis inhibition, and stimulation of neurite outgrowth, etc. This information will facilitate the application of mushroom-derived products in the treatment of AD. However, isolation of new metabolites from multiple types of mushrooms and further in vivo exploration of the molecular mechanisms underlying their antiAD effect are still required.

Background: Diabetic complications seriously endanger the health of most diabetic patients around the world. Most chemical hypoglycemic agents have adverse effects and are unable to improve the progression of diabetic complications. In recent years, a number of medicinal herbs have become increasingly popular for the treatment of diabetic complications due to their relative safety. Polysaccharides extracted from medicinal herbs with multiple pharmacological activities and low toxicity have been reported to be useful in the treatment of diabetic complications. Methods: Primary studies with keywords including polysaccharide and diabetic complications were retrieved from the Web of Science and NCBI databases and were read and analyzed. Results: Mushroom polysaccharides were proven to have positive effects on diabetic complications. Conclusions: We studied the effects of mushroom polysaccharides on hyperglycemia and as adjuvant therapies for diabetic complications and summarized the applications and limitations of mushroom polysaccharides to better understand their application for the treatment of diabetic complications.