ABSTRACT
This work reports novel chitosan functionalized graphene oxide (GO) nanocomposites combined fluorescence imaging and therapeutic functions in one agent, which can serve as a promising alternative to alleviate related diseases caused hyperinflammation. Briefly, GO was designed to be conjugated with chitosan, fluorescein-labeled peptide, toll-like receptor 4 antibody and hydroxycamptothecin/aloe emodin. We have demonstrated that such nanocomposites could effectively achieve active targeted delivery of pro-apoptotic and anti-inflammatory drugs into inflammatory cells and cause cells apoptosis by acid-responsive drug release. Moreover, confocal fluorescence imaging confirms that the drug-induced inflammatory cells apoptosis could be visualized the light-up fluorescence of fluorescein activated by caspase-3. Meanwhile, inflammatory-related biomarkers have down-regulated after the nanocomposites' treatment in both vitro and vivo experiments consistent with the results in histological sections. In summary, the bifunctional nanocomposites that possess anti-inflammation and fluorescence imaging could serve as a promising therapeutic agent for reducing hyperinflammation caused by numerous diseases.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Apoptosis/physiology , Drug Carriers/chemistry , Inflammation/drug therapy , Nanocomposites/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Antibodies/immunology , Camptothecin/analogs & derivatives , Camptothecin/chemistry , Camptothecin/therapeutic use , Cattle , Cell Line , Chitosan/chemistry , Drug Liberation , Emodin/chemistry , Emodin/therapeutic use , Fluorescent Dyes/chemistry , Graphite/chemistry , Humans , Lipopolysaccharides , Mammary Glands, Human/drug effects , Mammary Glands, Human/pathology , Mastitis/chemically induced , Mastitis/drug therapy , Mastitis/pathology , Mice , Toll-Like Receptor 4/immunologyABSTRACT
Emodin has shown pharmacological effects in the treatment of infection with severe acute respiratory syndrome coronavirus-2, which leads to coronavirus disease 2019 (COVID-19). Thus, we speculated that emodin may possess anti-COVID-19 activity. In this study, using bioinformatics databases, we screened and harvested the candidate genes or targets of emodin and COVID-19 prior to the determination of pharmacological targets and molecular mechanisms of emodin against COVID-19. We discovered core targets for the treatment of COVID-19, including mitogen-activated protein kinase 1 (MAPK1), tumor protein (TP53), tumor necrosis factor (TNF), caspase-3 (CASP3), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), interleukin 1B (IL1B), mitogen-activated protein kinase 14 (MAPK14), prostaglandin-endoperoxide synthase 2 (PTGS2), B-cell lymphoma-2-like protein 1 (BCL2L1), interleukin-8 (CXCL8), myeloid cell leukemia-1 (MCL1), and colony stimulating factor 2 (CSF2). The GO analysis of emodin against COVID-19 mainly included cytokine-mediated signaling pathway, response to lipopolysaccharide, response to molecule of bacterial origin, developmental process involved in reproduction, and reproductive structure development. The KEGG results exhibited that the molecular pathways mainly included IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, pertussis, proteoglycans in cancer, pathways in cancer, MAPK signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, etc. Also, molecular docking results revealed the docking capability between emodin and COVID-19 and the potential pharmacological activity of emodin against COVID-19. Taken together, these findings uncovered the targets and pharmacological mechanisms of emodin for treating COVID-19 and suggested that the vital targets might be used as biomarkers against COVID-19.
Subject(s)
COVID-19 Drug Treatment , Emodin/therapeutic use , Molecular Targeted Therapy , Protein Kinase Inhibitors/therapeutic use , Emodin/pharmacology , Humans , Molecular Docking Simulation , Protein Interaction Maps , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effectsABSTRACT
Critical care medicine is a medical specialty engaging the diagnosis and treatment of critically ill patients who have or are likely to have life-threatening organ failure. Sepsis, a life-threatening condition that arises when the body responds to infection, is currently the major cause of death in intensive care units (ICU). Although progress has been made in understanding the pathophysiology of sepsis, many drawbacks in sepsis treatment remains unresolved. For example, antimicrobial resistance, controversial of glucocorticoids use, prolonged duration of ICU care and the subsequent high cost of the treatment. Recent years have witnessed a growing trend of applying traditional Chinese medicine (TCM) in sepsis management. The TCM application emphasizes use of herbal formulation to balance immune responses to infection, which include clearing heat and toxin, promoting blood circulation and removing its stasis, enhancing gastrointestinal function, and strengthening body resistance. In this paper, we will provide an overview of the current status of Chinese herbal formulations, single herbs, and isolated compounds, as an add-on therapy to the standard Western treatment in the sepsis management. With the current trajectory of worldwide pandemic eruption of newly identified Coronavirus Disease-2019 (COVID-19), the adjuvant TCM therapy can be used in the ICU to treat critically ill patients infected with the novel coronavirus.