Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer's disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ1-42. In conclusion, spinosin reduced Aβ1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/ APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.

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In this study, we aimed to assess the possible impacts of essential oil (SEO) from Schisandra chinensis (Turcz.) Baill. (S. chinensis) on mice with cognition impairment.

Objectives Previous studies have suggested that spinosin (SPI) exerted neuroprotective effects through inhibition of oxidative damage, but the underlying mechanisms are still unclear. Herein, the mechanisms underlying the protective effects of SPI against oxidative stress induced by hydrogen peroxide (H 2 O 2) were examined in neuro-2a (N2a) mouse neuroblastoma cells. Methods N2a cells were pretreated with H 2 O 2 for 2 h, followed by a 24-h incubation with SPI. Intracellular reactive oxygen species (ROS) production was analysed by flow cytometry. Levels of Aβ 1-42 production were determined by ELISA assay. Levels of expression of c-Jun N-terminal kinase (JNK), p-JNK, extracellular signal-regulated kinase (ERK), pERK , p38 mitogen-activated protein kinase (p38MAPK), p-p38MAPK, p-Tau (Ser199), p-Tau (Ser202), p-Tau (Ser396), synaptophysin (SYP) and postsynaptic scaffold postsynaptic density-95 (PSD-95) were detected by Western blot analysis. Key findings Our results showed that H 2 O 2 treatment enhanced intracellular ROS production in N2a cells. SPI prevented H 2 O 2-induced oxidative damage via inhibiting Aβ 1-42 production, decreasing Tau phosphorylation and improving synaptic structural plasticity. Notably, H 2 O 2-increased p38MAPK activation was attenuated by SPI administration, and p38MAPK inhibitor BIRB796 markedly reduced H 2 O 2-induced oxidative damage in N2a cells. Conclusions Our findings suggest that SPI protects N2a cells from H 2 O 2induced oxidative damage through inactivation of p38MAPK.