LGM2605 / LignaMed, National Institute of Allergy and Infectious Diseases, Scripps Research Institute, University of Pennsylvania - LARVOL DELTA

A Synthetic Small Molecule, LGM2605: A Promising Modulator of Increased Pro-Inflammatory Cytokine and Osteoclast Differentiation by Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin. (PubMed, Dent J (Basel)) - "Moreover, immunoblotting showed reduced TRAP and cathepsin K levels, suggesting LGM2605's potential to curb osteoclast differentiation and maturation by modulating inflammatory cytokines, possibly involving Nrf2 activation. In summary, our research reveals the intricate connections between Cdt, pro-inflammatory cytokines, and osteoclast differentiation, offering novel therapeutic possibilities for managing these conditions."

Journal • Dental Disorders • Inflammation • Periodontitis • CTSK

Synthetic Secoisolariciresinol Diglucoside (LGM2605) Prevents Asbestos-Induced Inflammation and Genotoxic Cell Damage in Human Mesothelial Cells. (PubMed, Int J Mol Sci) - "Levels of MDA and 8-iso-PGF2α, markers of oxidative cell injury, were significantly (p < 0.001) reduced by 80.5% ± 0.1% and 76.6% ± 0.3%, respectively. LGM2605, given preventively, reduced ROS generation, DNA damage, and inflammasome-activated cytokine release and key inflammatory mediators implicated in asbestos-induced malignant transformation of normal mesothelial cells."

Journal • Immunology • Inflammation • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • HMGB1 • IL18 • IL1B • IL6 • TNFA

Late Inflammation Induced by Asbestiform Fibers in Mice Is Ameliorated by a Small Molecule Synthetic Lignan. (PubMed, Int J Mol Sci) - "LGM2605 countered these changes similarly among male and female mice, ameliorating late inflammation and altering immune responses in late post-LA exposure. These data support possible efficacy of LGM2605 in the prolonged treatment of LA-associated disease and other inflammatory conditions."

Journal • Preclinical • Immunology • Inflammation • Lung Cancer • Mesothelioma • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Copper Oxide Nanoparticle-Induced Acute Inflammatory Response and Injury in Murine Lung Is Ameliorated by Synthetic Secoisolariciresinol Diglucoside (LGM2605). (PubMed, Int J Mol Sci) - "CuO-NPs induced a significant inflammatory influx, inflammasome-relevant cytokine release, and chlorination damage in mouse lungs, which was mitigated by the action of LGM2605. Preventive action of LGM2605 ameliorated the adverse effects of CuO-NP in lung."

Journal • Preclinical • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • MPO

Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia. (PubMed, Int J Mol Sci) - "The addition of LGM2605 resulted in enhanced mitochondrial capacity, decreased lipid accumulation and amelioration of IL-1 β release in a model of defective lipid homeostasis. Collectively, these studies suggest that lipid overload decreases mitochondrial function and increases the inflammatory response, with LGM2605 acting as a protective agent."

Journal • Immunology • Inflammation • Metabolic Disorders

Short-term exposure to synthetic flaxseed lignan LGM2605 alters gut microbiota in mice. (PubMed, Microbiologyopen) - "The study here identifies for the first time significant alterations in the gut microbiota of mice following oral administration of LGM2605, in general shifting toward a more anti-inflammatory composition. These findings lay the foundation for future investigations utilizing LGM2605 to control gut dysbiosis and, by extension, systemic inflammation."

Journal • Preclinical • Immunology • Inflammation

Ozone-induced enhancement of airway hyperreactivity in rhesus macaques: Effects of antioxidant treatment. (PubMed, J Allergy Clin Immunol) - "ILC2s, CD1c myeloid dendritic cells, and CD4 T cells are selectively involved in O-induced asthma exacerbation. The inflammatory changes were partially prevented by antioxidant pretreatment with LGM2605, which had an unexpectedly disproportionate protective effect on AHR."

Journal • Asthma • Eosinophilia • Immunology • Respiratory Diseases

Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice. (PubMed, Toxicol Appl Pharmacol) - "Following acute exposure to Libby Amphibole (LA) asbestos-like fibers, synthetic secoisolariciresinol diglucoside (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases."

Journal • Preclinical • Immune Modulation • Immunology • Inflammation • Lung Cancer • Mesothelioma • Oncology • Respiratory Diseases • Solid Tumor • Thoracic Cancer

Antioxidant Gene Expression in Airway Smooth Muscle and Epithelial Cells is Upregulated by Synthetic Secoisolaricesinol Diglucoside (LGM2605) (AAAAI 2020) - "Our data suggest that airway smooth muscle is highly sensitive to oxidative stress as well as to the anti-oxidant effects of LGM2605 raising the potential of a novel treatment approach in asthma."

Radiation activates myeloperoxidase (MPO) to generate active chlorine species (ACS) via a dephosphorylation mechanism - inhibitory effect of LGM2605. (PubMed, Biochim Biophys Acta Gen Subj) - "We demonstrate that γ-radiation induces MPO-dependent generation of ACS, which is dependent, at least in part, by protein tyrosine and Ser/Thr dephosphorylation and is reduced by LGM2605. This study identified for the first time a novel protein dephosphorylation-dependent mechanism of radiation-induced MPO activation."

Journal • MPO

Chemically synthesized Secoisolariciresinol diglucoside (LGM2605) improves mitochondrial function in cardiac myocytes and alleviates septic cardiomyopathy. (PubMed, J Mol Cell Cardiol) - "In addition to protecting against cardiac dysfunction, daily treatment with LGM2605 and antibiotic ertapenem (70 mg/kg) protected against CLP-associated mortality and reversed hypothermia when compared against mice receiving ertapenem and saline. Therefore, treatment of septic mice with LGM2605 emerges as a novel pharmacological approach that reduces cardiac ROS accumulation, protects cardiac mitochondrial function, alleviates cardiac dysfunction, and improves survival."

Journal

FOXO1 Increases CardiοMyocyte KLF5 Expression, Which Induces Oxidative Stress, Lipotoxicity and Cardiomyopathy in Type 1 Diabetes (AHA 2019) - "Antioxidant treatment (LGM2605) of αMHC-rtTA- Klf5 mice and diabetic C57BL/6 mice, improved cardiac dysfunction partially...In conclusion, we show that FOXO1 can induce KLF5 in cardiomyocytes, which drives DbCM in a PPARα-independent manner. Thus, KLF5 inhibition holds promise as a therapeutic intervention for DbCM."

FOXO1 • KLF5

Cardiomyocyte-KLF5 Expression is Increased by FOXO1 and Accounts for Cardiomyopathy in Type-1 Diabetes (BCVS 2019) - "Accordingly, mice with doxycycline-mediated cardiomyocyte-specific KLF5 constitutive expression (αMHC-rtTA-Klf5) recapitulated cardiomyopathy even in the absence of T1D. Treatment of αMHC-rtTA-Klf5 mice and diabetic C57BL/6 mice with the antioxidant LGM2605 improved partially cardiac dysfunction. In conclusion, cardiomyocyte KLF5 expression is activated by FOXO1 and drives diabetic cardiomyopathy in a non-PPARα-dependent manner, suggesting KLF5 inhibition as a therapeutic intervention in T1D cardiomyopathy."