Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice

Abstract

Background: Exposure to the Libby Amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice.Methods: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 μg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry.Results: LA exposure induced a significant increase (p<0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p<0.0001) elevated post-LA exposure, and were significantly (p<0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells.

Secoisolariciresinol Diglucoside Exerts Anti-Inflammatory and Antiapoptotic Effects through Inhibiting the Akt/IκB/NF-κB Pathway on Human Umbilical Vein Endothelial Cells

“…Moreover, NO metabolites can interact with endothelial damage, inflammation, and vascular disease [27,28]. We also found that SDG inhibits the expression of proinflammatory cytokines, which is consistent with our previous and other findings [11,29]. Studies have shown that immune inflammation is a key factor in the development of cardiovascular disease.…”

Short‐term exposure to synthetic flaxseed lignan LGM2605 alters gut microbiota in mice

“…In the present study, we utilized the synthetic flaxseed lignan LGM2605 as a form of dietary intervention in mice. Previous studies have shown that LGM2605 acts as an antioxidant and free radical scavenger (Pietrofesa, Velalopoulou, Arguiri, et al, 2016), reducing inflammation associated with radiation and asbestos exposure (Christofidou‐Solomidou et al, 2019; Mishra et al, 2020; Velalopoulou et al, 2015); however, its effects on gut microbiota have not previously been evaluated. We therefore sought to determine how a 10‐day period of oral LGM2605 administration affects the gut microbial composition of mice.…”

“…Recently, the synthetic flaxseed lignan LGM2605 has been evaluated as a therapeutic alternative to naturally occurring SDG, as it has significantly greater bioavailability compared to whole flaxseed and can be readily produced in a laboratory setting (Mishra et al, 2013). Previous studies have demonstrated the usefulness of LGM2605 in controlling inflammation and oxidative stress responses in models of radiation and asbestos exposure, likely resulting from the ability of LGM2605 to scavenge radical species and reduce inflammatory cytokine production (Christofidou‐Solomidou et al, 2019; Mishra et al, 2020; Pietrofesa et al, 2014; Pietrofesa, Velalopoulou, Arguiri, et al, 2016; Velalopoulou et al, 2015). The protective effects of LGM2605 may be especially important in lung and breast cancer radiation therapies to reduce damage to bystander organs (Velalopoulou et al, 2017).…”

Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia

“…SDG is a potent antioxidant with anti-inflammatory and antifibrotic properties; the beneficial effects of SDG have been documented in treating hypercholesterolemia, diabetes, postmenopausal symptoms, cardiovascular disease, metabolic syndrome, bone disease, ischemia-reperfusion injury, radiation-induced pneumonopathy and hyperoxia [ 69 ], and references therein. Chemically synthesized SDG, LGM2605 is effective in several preclinical models of disease in which oxidative stress and inflammation play a prominent role in pathogenesis [ 35 , 39 , 40 , 41 ]. Herein, we show for the first time that LGM2605 protects the RPE against lipid overload and oxidative stress mediated cytokine release.…”

“…SDG has potent free radical scavenging and antioxidant properties and confirms its DNA radioprotective properties in cell-free systems [ 36 ] as well as in cells [ 37 , 38 ]. In preclinical models in mice [ 35 , 39 , 40 , 41 ], non-human primates [ 42 ] and in an ex vivo lung organ culture model of proton-irradiated human lung, LGM2605 [ 43 ] has been shown to be highly efficacious. LGM2605 exhibits free radical scavenging, antioxidant and anti-inflammatory properties in diverse inflammatory cells (Rom, 2018 #43; Kokkinaki, 2019 #38; Christofidou-Solomidou, 2012 #55; Mishra, 2013 #48; Velalopoulou, 2017 #47; Velalopoulou, 2015 #42; Pietrofesa, 2016 #62; Pietrofesa, 2017 #54).…”