Background Diabetes is a serious global health concern which severely affected public health as well as socio-economic growth worldwide. Scutellarin (SCU), a bioactive flavonoid, is known for its efficacious action against a range of ailments including cardiovascular problems. The present study was conducted to find out possible protective effect and its associated mechanisms of SCU on experimental type 2 diabetes-induced cardiac injury. Methods Type 2 diabetes was induced by treating animals with high fat diet for 4 weeks and a single intraperitoneal dose (35 mg/kg body weight) of streptozotocin and diabetic animals received SCU (10 or 20 mg/kg/day) for 6 weeks. Results Scutellarin attenuated type 2 diabetes-induced hyperglycemia, bodyweight loss, hyperlipidaemia, cardiac functional damage with histopathological alterations and fibrosis. Scutellarin treatment to type 2 diabetic mice ameliorated oxidative stress, inflammatory status and apoptosis in heart. Furthermore, the underlying mechanisms for such mitigation of oxidative stress, inflammation and apoptosis in heart involved modulation of Nrf2/Keap1 pathway, TLR4/MyD88/NF-κB mediated inflammatory pathway and intrinsic (mitochondrial) apoptosis pathway, respectively. Conclusions The current findings suggest that SCU is effective in protecting type 2 diabetes-induced cardiac injury by attenuating oxidative stress and inflammatory responses and apoptosis, and it is also worth considering the efficacious potential of SCU to treat diabetic cardiomyopathy patients.
The present study aims to explore the role of microRNA 145-5p (miR-145-5p) in hyperlipidemia. Using bioinformatics tools and a wide range of function and mechanism assays, we attempted to understand the specific function and potential mechanism of miR-145-5p in hyperlipidemia. A cholesterol-enriched diet induced an increase of serum cholesterol and triacylglycerol but a decrease of serum high-density lipoprotein. MiR-145-5p level was decreased in hyperlipidemia rat models. MiR-145-5p regulated lipid metabolism by antagonizing the alteration of high-density lipoprotein, cholesterol, and triacylglycerol in serum mediated by a cholesterol-enriched diet. In mechanism, miR-145-5p directly bound with p21 protein (RAC1)-activated kinase 7 (PAK7) and negatively regulated mRNA and protein levels of PAK7 in THP-1 cells. Furthermore, miR-145-5p level was negatively associated with PAK7 level in rat cardiac tissues. Finally, overexpression of PAK7 reversed the effects of miR-145-5p on β-catenin activation and M2 macrophages polarization in THP-1 cells. In conclusion, MiR-145-5p modulated lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia, which may provide a potential biomarker for the treatment of hyperlipidemia-induced cardiovascular diseases.
To use bioinformatics and network analysis to reveal the mechanism of "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair in the treatment of lung adenocarcinoma. The target and pathway of "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair in the treatment of lung adenocarcinoma were explored by online databases and network analysis tools, and the potential biomarkers of "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair in the treatment of lung adenocarcinoma were predicted in reverse. A total of 59 traditional Chinese medicine compounds and 510 drug targets were screened in this study. A total of 25 micro-RNAs and 15,323 disease targets were obtained through GEO2R software analysis. In the end, 294 therapeutic targets and 47 core targets were obtained. A total of 186 gene ontology enrichment assays were obtained, and core therapeutic targets play multiple roles in biological processes, molecular functions, and cellular composition. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the core targets were mainly enriched in cancer-related pathways, immune-related pathways, endocrinerelated pathways, etc, among which the non-small cell lung cancer pathway was the most significant core pathway. Molecular docking shows that the compound and the target have good binding ability. "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair plays a mechanism of action in the treatment of lung adenocarcinoma through multiple targets and pathways. miR-5703, miR-3125, miR-652-5P, and miR-513c-5p may be new biomarkers for the treatment of lung adenocarcinoma.Abbreviations: EGFR = epidermal growth factor receptor, FoxO = forkhead box O, GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes, LUAD = lung adenocarcinoma, miRNA = micro RNA, PPI = protein-protein interaction.
Background: Diabetes is a serious global health concern which severely affected public health as well as socio-economic growth worldwide. Scutellarin (SCU), a bioactive flavonol is known for its efficacious action against a range of ailments including cardiovascular problems. The present study conducted to find out possible protective effect and its associated mechanisms of SCU on experimental type 2 diabetes-induced cardiac injury.Methods: Type 2 diabetes was induced by treating animals with high fat diet for 4 weeks and a single intraperitoneal dose (35 mg/kg body weight) of streptozotocin and diabetic animals received SCU (10 or 20 mg/kg/day) for 6 weeks.Results: SCU attenuated type 2 diabetes-induced hyperglycemia, body weight loss, hyperlipidemia, cardiac functional damage with histo-pathological alterations and fibrosis. SCU treatment to type 2 diabetic mice exacerbated oxidative stress, inflammatory status and apoptosis in heart. Furthermore, the underlying mechanisms for such mitigation of oxidative stress, inflammation and apoptosis in heart involved modulation of Nrf2/Keap1 pathway, TLR4/MyD88/NF-κB mediated inflammatory pathway and intrinsic (mitochondrial) apoptosis pathway, respectively.Conclusions: The current findings suggest that SCU is effective in protecting type 2 diabetes-induced cardiac injury by attenuating oxidative stress and inflammatory responses and apoptosis and it is also worth considering the efficacious potential of SCU to treat diabetic cardiomyopathy patients.
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