Introduction: Progressive accumulation of amyloid-β (Aβ) is a pathological trait of Alzheimer's disease (AD). Amyloid-β increases free radical production in neuronal cells, leading to neuronal cell death. Hormone replacement therapy can reduce the incidence of AD, and oestrogen significantly improves the clinical signs in patients with AD. However, the long-term use of oestrogen causes a variety of diseases. Phytoestrogens have been reported to bind and activate oestrogen receptors in mammals and humans to produce oestrogen-like or anti-oestrogen-like effects. Kaempferol is a flavonoid phytoestrogen that can produce a certain protective effect in neurons. However, the molecular mechanism of kaempferol in AD is unclear. Material and methods: This study used pheochromocytoma (PC-12) cells that were damaged by Aβ 25-35 as an in vitro model of AD, and oestradiol was a positive control. The cells were incubated with kaempferol alone or in combination with fulvestrant (an antagonist of ER) and U0126 (an inhibitor of ERK) in Aβ 25-35 culture. Cell activity was measured by the MTT method. Cell apoptosis was evaluated by flow cytometry. Gene and protein expression levels were tested by qRT-PCR and Western blotting. Results: This study demonstrated that kaempferol protected PC-12 cells from Aβ 25-35-induced cell death and apoptosis in a dose-dependent manner. Treatment with fulvestrant (an antagonist of ER) and U0126 (an inhibitor of ERK) significantly increased the apoptosis of PC-12 cells. Moreover, kaempferol promoted the expression of anti-apoptotic molecules and inhibited the expression of pro-apoptotic molecules, which were blocked by fulvestrant and U0126. Conclusions: Kaempferol protected PC-12 cells against Aβ 25-35-induced cell apoptosis through the ER/ERK/MAPK signalling pathway.
Secreted protein acidic and rich in cysteine (SPARC), also termed osteonectin or BM-40, is a matricellular protein which regulates cell adhesion, extracellular matrix production, growth factor activity, and cell cycle. Although SPARC does not perform a structural function, it, however, modulates interactions between cells and the surrounding extracellular matrix due to its anti-proliferative and anti-adhesion properties. The overexpression of SPARC at sites, including injury, regeneration, obesity, cancer, and inflammation, reveals its application as a prospective target and therapeutic indicator in the treatment and assessment of disease. This article comprehensively summarizes the mechanism of SPARC overexpression in inflammation and tumors as well as the latest research progress of functional nanomaterials in the therapy of rheumatoid arthritis and tumors by manipulating SPARC as a new target. This article provides ideas for using functional nanomaterials to treat inflammatory diseases through the SPARC target. The purpose of this article is to provide a reference for ongoing disease research based on SPARC-targeted therapy.
Alzheimer’s disease (AD) is the most common form of dementia and a significant social and economic burden. Estrogens can exert neuroprotective effects and may contribute to the prevention, attenuation, or even delay in the onset of AD; however, long-term estrogen therapy is associated with harmful side effects. Thus, estrogen alternatives are of interest for countering AD. Naringin, a phytoestrogen, is a key active ingredient in the traditional Chinese medicine Drynaria. Naringin is known to protect against nerve injury induced by amyloid beta-protein (Aβ) 25–35, but the underlying mechanisms of this protection are unclear. To investigate the mechanisms of naringin neuroprotection, we observed the protective effect on Aβ25–35-injured C57BL/6J mice’s learning and memory ability and hippocampal neurons. Then, an Aβ25–35 injury model was established with adrenal phaeochromocytoma (PC12) cells. We examined the effect of naringin treatment on Aβ25–35-injured PC12 cells and its relationship with estrogen receptor (ER), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and glycogen synthase kinase (GSK)-3β signaling pathways. Estradiol (E2) was used as a positive control for neuroprotection. Naringin treatment resulted in improved learning and memory ability, the morphology of hippocampal neurons, increased cell viability, and reduced apoptosis. We next examined the expression of ERβ, p-AKT (Ser473, Thr308), AKT, p-GSK-3β (Ser9), GSK-3β, p-Tau (Thr231, Ser396), and Tau in PC12 cells treated with Aβ25–35 and either naringin or E2, with and without inhibitors of the ER, PI3K/AKT, and GSK-3β pathways. Our results demonstrated that naringin inhibits Aβ25–35-induced Tau hyperphosphorylation by modulating the ER, PI3K/AKT, and GSK-3β signaling pathways. Furthermore, the neuroprotective effects of naringin were comparable to those of E2 in all treatment groups. Thus, our results have furthered our understanding of naringin’s neuroprotective mechanisms and indicate that naringin may comprise a viable alternative to estrogen therapy.
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