Progressive macrophage dysfunction and apoptosis are some of the major events that occur during atherogenesis. To further investigate the intrinsic association between atherosclerosis (AS) and macrophage apoptosis and autophagy, cholesterol crystals (CHCs) were used to stimulate RAW264.7 macrophages to establish a macrophage model of advanced AS. Cells in the CHC group were treated with salvianolic acid B (Sal B) to evaluate its protective effects and reveal its underlying molecular mechanism. The results demonstrated that treatments with Sal B significantly improved autophagy dysfunction and reduced the apoptotic rate of CHC-induced macrophages. Furthermore, Sal B significantly attenuated CHC-induced release of proinflammatory factors (TNF-α and IL-6) by macrophages. Treatment of macrophages with a specific inhibitor of autophagy (3-methyladenine) significantly reversed Sal B-mediated effects on autophagy, suggesting that Sal B-induced autophagy may display a protective effect in CHC-induced macrophages. Furthermore, pretreatment of CHC-induced macrophages with insulin significantly decreased Sal B-induced autophagy, indicating that the Akt/mTOR signaling pathway may serve as a critical mediator in regulating Sal B-mediated cell death. Taken together, the present study demonstrated that Sal B improved autophagic dysfunction and reduced the apoptosis of CHC-induced macrophages via inhibiting the Akt/mTOR signaling pathway.

Purpose To investigate the molecular mechanism of Croci stigma (CS) in the treatment of melasma by network pharmacology and molecular docking. Methods TCMSP, CTD, STITCH, SymMap, GeneCard, GenBank, OMIM and DrugBank databases were used to obtain the components and targets of CS and the targets of chloasma. STRING was used to build a protein–protein interaction (PPI) network of intersecting targets between drugs and diseases. Cytoscape was used to establish drug‐compounds‐targets‐disease network and analyze PPI network. R was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and visualization. AutoDock was used for molecular docking and R was used to visualize docking results. Results Four active compounds were screened out from CS, and 31 target genes intersecting with melasma were found after further analysis. The top 10 hub genes were found after analysis of the PPI network, including TYR, TYRP1, DCT, CREB1, KITLG, MITF, ESR1, EDNRB, CD4, and PTGS2. In the enrichment analysis, melanogenesis was considered as the core pathway through which CS exerts its therapeutic effect on melasma. Molecular docking results showed that the core genes in the regulatory network had high binding activity with related active components, especially crocetin. Conclusion CS may treat melasma by regulating core targets, such as TYR, TYRP1, DCT, CREB1, KITLG, MITF, EDNRB, and PTGS2, and acting on melanogenesis. And crocetin may be the core compound worthy of further study.

Objective. To explore the role and mechanism of BKCa in diabetic kidney disease. Methods. Rat mesangial cells (MCs) HBZY-1 were cultured with high glucose to simulate the high-glucose environment of diabetic kidney disease in vivo. The effects of large conductance calcium-activated potassium channel (BKCa) on proliferation, migration, and apoptosis of HBZY-1 cells were observed. The contents of transforming growth factor beta 1 (TGF-β1), Smad2/3, collagen IV (Col IV), and fibronectin (FN) in the extracellular matrix were also observed. Results. High glucose significantly damaged HBZY-1 cells, which enhanced the ability of cell proliferation, migration, and apoptosis, and increased the secretion of Col IV and FN. Inhibition of BKCa and TGF-β1/Smad2/3 signaling pathways can inhibit the proliferation, migration, and apoptosis of HBZY-1 cells and suppress the secretion of Col IV and FN. The effect of excitation is the opposite. Conclusions. BKCa regulates mesangial cell proliferation, migration, apoptosis, and secretion of Col IV and FN and is associated with TGF-β1/Smad2/3 signaling pathway.

Objective: The aim of this study was to examine the effect of berberine in diabetes mellitus in vivo and in vitro, and elucidate the underlying mechanisms. Methods: Rat models of type 2 diabetes mellitus (T2DM) were established, which were treated with berberine. Pathological changes in the thoracic aorta, and inflammatory factor and adiponectin levels were investigated. Vascular smooth muscle cells (VSMCs) of the thoracic aorta were cultured and treated with berberine. Cellular proliferation, migration, and inflammatory factor levels were investigated. Responses of vascular rings to phenylephrine (PE) and sodium nitroprusside (SNP) after berberine intervention, and the changes of relaxation responses to SNP after adding Iberiotoxin (IbTX) were investigated. Results: Berberine ameliorated the pathological status of the thoracic aorta in the T2DM rats. Berberine significantly inhibited the C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and increased the adiponectin level compared with the model group. Compared with the model group, berberine inhibited the proliferation and migration of VSMCs in vitro, and reduced tumor growth factor-β1 (TGF-β1), IL-6, and TNF-α levels. Furthermore, the contraction of thoracic aorta to PE was reduced, while the relaxation response of thoracic aorta to SNP was increased, after the berberine intervention in the T2DM rats. The relaxation of thoracic aorta to SNP in the model and berberine groups were decreased after the IbTX treatment. Conclusions: Protective effects of berberine against macrovascular complications induced by diabetes mellitus may be attributed to inhibiting the inflammation and intervening the calcium-activated potassium (BKCa).