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Canagliflozin Inhibits Human Endothelial Cell Proliferation and Tube Formation
In conclusion, the present study identified canagliflozin as a potent inhibitor of human EC proliferation. The anti-proliferative action of canagliflozin is observed in ECs isolated from both the venous and arterial circulation, and is partly due to the blockade of cyclin A expression. In addition, this study found that canagliflozin inhibits tube formation in cultured ECs and mouse aortic rings. Notably, these actions are specific for canagliflozin and not seen with other SGLT2 inhibitors. The ability of canagliflozin to exert these pleiotropic effects on EC function may contribute to both the adverse and salutary actions...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

6-Bromoindirubin-3 ′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver
In this study, we aimed to investigate the anti-aging effect, and molecular mechanism, of the novel anti-aging drug 6BIO on naturally aged mouse liver. Rapamycin, a well-known promising anti-aging drug that delays aging through mTOR-dependent autophagy (Zhou and Ye, 2018), was used as the positive control in the study. To our knowledge, this is the first study to demonstrate the effects of 6BIO treatment in models of natural aging. Our results indicated that 6BIO ameliorates the decline of liver function with age, including lipid metabolism disorder, and attenuates hepatocyte senescence in aged mice, as revealed by altera...
Source: Frontiers in Pharmacology - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Nrf2 as a Potential Mediator of Cardiovascular Risk in Metabolic Diseases
Conclusion Activation of the Nrf2-dependent antioxidant system plays an important role in cell defense against oxidative stress damage, whereas the insufficiency of the Nrf2 system is associated with multiple aspects of the genesis and progression of metabolic diseases, posing a great risk to the cardiovascular system (Figure 1). The systemic increase of Nrf2 activity by several activators may be beneficial in the treatment of metabolic diseases. In addition, selective upregulation of Nrf2 genes may represent a potential therapy in obesity, diabetes and atherosclerosis. Looking to the future, experimental research that el...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Podoplanin: Its roles and functions in neurological diseases and brain cancers
Podoplanin is a small mucin-like glycoprotein involved in several physiological and pathological processes in the brain including development, angiogenesis, tumors, ischemic stroke and other neurological disorders. Podoplanin expression is upregulated in different cell types including choroid plexus epithelial cells, glial cells, as well as periphery infiltrated immune cells during brain development and neurological disorders. As a transmembrane protein, podoplanin interacts with other molecules in the same or neighboring cells. In the past, a lot of studies reported a pleiotropic role of podoplanin in the modulation of th...
Source: Frontiers in Pharmacology - September 13, 2022 Category: Drugs & Pharmacology Source Type: research