RESUMO
OBJECTIVE: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. CONCLUSION: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.
RESUMO
Objective: To investigate the mechanism underlying the effects of berberine (BBR) in the treatment of Alzheimer's disease (AD). Methods: 3 × Tg AD mice were treated with BBR for 3 months, then the open field test (OFT), the novel object recognition test (NOR) and the Morris water maze (MWM) test were performed to assess behavioral performance. Hematoxylin-eosin (HE) staining, Nissl staining were used to examine histopathological changes. The pharmacological and molecular properties of BBR were obtained from the TCMSP database. BBR-associated AD targets were identified using the PharmMapper (PM), the comparative toxicogenomics database (CTD), DisGeNet and the human gene database (GeneCards). Core networks and BBR targets for the treatment of AD were identified using PPI network and functional enrichment analyses. AutoDock software was used to model the interaction between BBR and potential targets. Finally, RT-qPCR, western blotting were used to validate the expression of core targets. Results: Behavioral experiments, HE staining and Nissl staining have shown that BBR can improve memory task performance and neuronal damage in the hippocampus of AD mice. 117 BBR-associated targets for the treatment of AD were identified, and 43 genes were used for downstream functional enrichment analysis in combination with the results of protein-protein interaction (PPI) network analysis. 2,230 biological processes (BP) terms, 67 cell components (CC) terms, 243 molecular function (MF) terms and 118 KEGG terms were identified. ALB, EGFR, CASP3 and five targets in the PI3K-AKT signaling pathway including AKT1, HSP90AA1, SRC, HRAS, IGF1 were selected by PPI network analysis, validated by molecular docking analysis and RT-q PCR as core targets for further analysis. Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment (p < 0.05). Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels. Conclusion: AKT1, HSP90AA1, SRC, HRAS, IGF1 and ALB, EGFR, CASP3 were core targets of BBR in the treatment of AD. BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways.
RESUMO
BACKGROUND: Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis Georgi, has shown potential pharmacological effects on myocardial ischemia diseases. Nevertheless, systematic preclinical studies on baicalin in the treatment of ischemic diseases are scarce. PURPOSE: To assess the efficacy and potential mechanisms of baicalin in myocardial ischemia (RI), myocardial ischemia-reperfusion (IR) injury and myocardial infarction (MI) animal models for future clinical research. METHODS: Preclinical studies published prior to August 27th, 2022 were retrieved from PubMed, Embase, Web of Science and Cochrane Library. CAMARADES list was used to evaluate the quality of included researches. Meta-analyses of cardiac pathology and function parameters, myocardial injury markers and other indicators were performed by STATA 15.0 software. Potential mechanisms are categorized and summarized. Dose-response interval analyses were used to analyze the dose-response relationship between baicalin and myocardial ischemia disease. RESULTS: Fourteen studies and 222 animals were included in the analysis. The results showed that compared with the control group, baicalin could reduce myocardial infarction size associated with cardiac pathological condition and the corresponding cardiac pathological index containing CK-MB, CK and cTnT. Additionally, heart function indicators including LVSP, LVFS, LVEF, -dp/dt max, dp/dt max were increased by baicalin. As for subgroup analyses, baicalin also demonstrated certain effect on CK-MB and LVSP by administration method or stage. Furthermore, it displayed obvious effect on myocardial ischemia diseases when the dose is maintained at 100-150 mg/kg based on dosage analyses. CONCLUSION: Based on the relevant literature retrieved, this is the first meta-analysis on baicalin in treating myocardial ischemia diseases. Notably, we linked the dynamic development of the disease and discussed it pertinently, from RI, IR injury to MI. Baicalin exhibits positive effects on myocardial ischemia diseases (especially when the dose is 100-150 mg/kg), which is achieved by regulating key pathological indicators and various signaling pathways.
