Shengnan Yang,Yuan Zhang,Fukui Shen,Xiaoyao Ma,Man Zhang,Yuanyuan Hou,Gang Bai
Baicalin is one of the main flavonoids of the dried root of Scutellaria baicalensis Georgi and is reported to exert beneficial effects on the regulation of glucose/lipid metabolism. However, understanding its specific target and unique mechanism for improving glucose utilization is a challenge. In this paper, target fishing with a baicalin probe reveals that baicalin interacts with AKT. An immunofluorescence assay further demonstrates the colocalization of baicalin with AKT in the cytoplasm. A competitive test and virtual docking show that baicalin might bind to the pleckstrin homology domain of AKT. This specific binding hampers AKT membrane translocation, activates the phosphorylation of AKT on Ser473, induces the downstream glycogen synthase kinase 3β activation, and affects glycogen synthesis.
Wei Wei,Bingwei Yang,Xiangyu Zhu,Xuting Liu,Erqun Song,Yang Song
When nanoparticles (NPs) enter a physiological environment, they tend to adsorb proteins to form a so-called corona. A comprehensive understanding of the effect of protein corona on NPs’ toxicity is required. Our previous study indicated that silica nanoparticles (SiO2 NPs) exposure with different routes resulted in distinct brain damage; however, an exact molecular mechanism of protein corona on the regulation of SiO2 NPs-induced damages needs further investigation. SiO2 NPs exposure via intravenous injection may encounter a protein-rich bio-matrix, which drives the adsorption of serum protein on their surface to form a stable SiO2 NPs@serum complex. On the contrary, SiO2 NPs exposure via intranasal instillation remained their original feature, due to a protein infertile environment of cerebrospinal fluid. Apparently, surface adsorption of proteinaceous substances altered inherent toxic behavior of SiO2 NPs. In addition, glycogen synthase kinase 3 beta (GSK3β) phosphorylate was found at different residues, which play an essential role in orchestrating apoptosis and autophagy threshold. Route-dependent corona formation determined GSK3β phosphorylation status and ultimately the toxic behavior of SiO2 NPs. This work presented the evidence of bio-corona on the regulation of SiO2 NPs-induced toxicity, which can be used to guide risk assessment of environmental NPs.
Jinhua Hu,Zhao Mao,Shuangcheng He,Yuanran Zhan,Rui Ning,Wei Liu,Bingfang Yan,Jian Yang
Osteoporosis is a serious public health concern worldwide. Herba epimedii has been used for centuries and even thousands of years to treat osteoporotic conditions. Icariin , a flavonol glycoside , is one of the major active ingredients. In this study, we have shown that icariin protected against glucocorticoid-induced osteoporotic changes in SaoS-2 cells and mice. We have also shown that dexamethasone (a glucocorticoid) suppressed and icariin induced DEC1, a structurally distinct helix-loop-helix protein. DEC1 overexpression promoted whereas DEC1 knockdown decreased osteogenic activity. Likewise, DEC1 overexpression and knockdown inversely regulated the expression of β-catenin and PIK3CA, an essential player in the Wnt/β-catenin and PI3K/Akt signaling pathways, respectively. Interestingly, DKK1, an inhibitor of Wnt/β-catenin signaling inhibitor, and LY294002 , an inhibitor of PI3K/Akt signaling, abolished the induction of DEC1 by icariin. It is established that these two pathways are interconnected by the phosphorylation status of GSK3β. Dexamethasone decreased but icariin increased GSK3β phosphorylation. Finally, DEC1 deficient mice developed osteoporotic phenotypes. Taken together, it is concluded that DEC1 likely supports the action of icariin against glucocorticoid induced osteoporosis with an involvement of the PI3K/Akt/GSK3β/β-catenin integrated signaling pathway.
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