Lisofylline: a potential lead for the treatment of diabetes.

@article{Yang2005LisofyllineAP,
  title={Lisofylline: a potential lead for the treatment of diabetes.},
  author={Zandong Yang and Meng Chen and Jerry L Nadler},
  journal={Biochemical pharmacology},
  year={2005},
  volume={69 1},
  pages={
          1-5
        }
}
Lisofylline (LSF), a synthetic modified methylxanthine, was originally designed and tested as an agent to reduce mortality during serious infections associated with cancer chemotherapy. Experimental studies and several clinical trials showed that LSF inhibited the generation of phosphatidic acid and free fatty acids. LSF also blocked the release of pro-inflammatory cytokines in oxidative tissue injury, in response to cancer chemotherapy and in experimental sepsis. Recent research has revealed a… Expand
Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes.
TLDR
It is found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal, suggesting that such combined therapy could become a new strategy to defeat T1DM in humans. Expand
Self-assembling lisofylline-fatty acid conjugate for effective treatment of diabetes mellitus.
TLDR
LSF-LA micelles exhibited reduced protein binding, significantly higher half-life, and higher apparent volume of distribution than free LSF, and reduced blood glucose levels were observed at a reduced dose that was further confirmed by immunohistochemical analysis. Expand
A new approach for treatment of type 1 diabetes: Phytotherapy and phytopharmacology of regulatory T cells
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It was found that Uncaria tomentosa, Dioscorea alata, Cordyceps sinensis, Origanum vulgare, TJ-48, compound K, azaspirane, lisofylline, and curcumin can promote the function of Tregs in T1D. Expand
Lisofylline mitigates cardiac inflammation in a mouse model of obesity through improving insulin secretion and activating cardiac AMPK signaling pathway.
TLDR
It is observed that LSF alleviated obesity-induced cardiac injury indirectly by improving both pancreatic β-cell function and insulin sensitivity, as well as, directly via upregulation of cardiac AMPK expression and down regulation of cardiac inflammation and apoptosis, may represent an effective therapy targeting Obesity-induced metabolic and cardiovascular complications. Expand
Pharmacokinetic-Pharmacodynamic Modeling of Methylxanthine Derivatives in Mice Challenged with High-Dose Lipopolysaccharide
  • E. Wyska
  • Medicine, Chemistry
  • Pharmacology
  • 2010
TLDR
It seems that pentoxifylline is more potent than lisofylline in inhibiting TNF-α production in vivo, and may be helpful in appropriate dosage selection for further studies. Expand
Pentoxifylline and its major oxidative metabolites exhibit different pharmacological properties.
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M5, retaining some of the PTX effects but lacking in significant inhibition of TNF-alpha production, may be a promising candidate drug for certain pathologic conditions. Expand
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TLDR
It is demonstrated that LSF profoundly enhances β‐cell function, and the potential of using inflammatory blockade, such as LSF, to improve β‐ cell function for islet transplantation is suggested. Expand
Enantioselective reduction of pentoxifylline to lisofylline using whole‐cell Lactobacillus kefiri biotransformation
Lisofylline (LSF) is a drug candidate that has been under investigation for acute respiratory distress syndrome, acute lung injury, septic shock and mucositis. As LSF is not commercially available inExpand
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TLDR
It is proposed that the combination of PTX + DIP can be used in both early and advanced stages of COVID-19, and concurrent use of certain nutraceuticals – yeast beta-glucan, zinc, vitamin D, spirulina, phase 2 inducers, N-acetylcysteine, glucosamine, quercetin, and magnesium – might also improve therapeutic outcomes in COVIDs. Expand
Physiologically based modeling of lisofylline pharmacokinetics following intravenous administration in mice
TLDR
The mouse is a good model to study LSF pharmacokinetics following intravenous administration and the developed PBPK model may be useful to design future preclinical and clinical studies of this compound. Expand
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References

SHOWING 1-10 OF 61 REFERENCES
The Novel Anti-inflammatory Compound, Lisofylline, Prevents Diabetes in Multiple Low-Dose Streptozotocin-Treated Mice
TLDR
This study suggests that treatment with LSF suppresses proinflammatory cytokines and protects islet insulin secretion and cells from inflammation, and may be useful for prevention of type 1 diabetes and other disorders associated with excessive pro inflammatory cytokines. Expand
Lisofylline causes rapid and prolonged suppression of serum levels of free fatty acids.
TLDR
The effects of L SF on lipid metabolism were present for a prolonged period compared with measurable persistence in plasma; this points to unique functions or unknown metabolites of LSF. Expand
Lisofylline, an inhibitor of unsaturated phosphatidic acid generation, ameliorates interleukin-1 beta-induced dysfunction in cultured rat islets.
TLDR
It is suggested that LSF is effective in reducing IL-1 beta-induced islet dysfunction, thus supporting the role of lipid mediators such as PA in cytokine- induced islet toxicity. Expand
The anti-inflammatory compound lisofylline prevents Type I diabetes in non-obese diabetic mice
TLDR
Lisofylline prevents the onset of autoimmune diabetes in NOD mice by a mechanism that does not seem to enhance the function of regulatory T cells, but could be associated with suppression of proinflammatory cytokines and reduction of cellular infiltration in islets. Expand
Lisofylline, a Novel Antiinflammatory Agent, Protects Pancreatic β-Cells from Proinflammatory Cytokine Damage by Promoting Mitochondrial Metabolism.
TLDR
To examine the direct effects of LSF on β-cells, insulin-secreting INS-1 cells were exposed to a combination of recombinant IL-1β, TNFα, and IFNγ with or without LSF for 18 h and cell viability was determined. Expand
The novel anti-inflammatory agent lisofylline prevents autoimmune diabetic recurrence after islet transplantation1
TLDR
It is demonstrated that autoimmune diabetes recurrence after islet transplantation could be prevented by treatment with LSF, and LSF and its analogues may have the potential to prevent islet autoimmune destruction in clinical transplantation. Expand
The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs.
TLDR
Inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Expand
Effects of lisofylline on hyperoxia-induced lung injury.
TLDR
It is suggested that lisofylline ameliorates hyperoxia-induced lung injury and mortality through inhibiting CREB activation, membrane oxidation, and proinflammatory cytokine expression in the lungs. Expand
Lisofylline decreases white cell adhesiveness and improves survival after experimental hemorrhagic shock.
TLDR
Lisofylline improves survival in this model of hemorrhagic shock and its beneficial effect may be related to down-regulation of leukocyte adhesiveness. Expand
Diabetes Induced with Low Doses of Streptozotocin is Mediated by Vβ8.2+ T-Cells
TLDR
It is concluded that there is limited heterogeneity of the T-cell response that causes diabetes in MDSDM, and a limited number of Vβ8.2+ cells are preferentially expanded in the islets in the early stages. Expand
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