Methylene Blue Mitigates Acute Neuroinflammation after Spinal Cord Injury through Inhibiting NLRP3 Inflammasome Activation in Microglia

Lin, Zhiyong; Wang, Siyuan; Chen, Lili; Zhuang, Jian; Ke, Qingfeng; Xiao, Dan-Rui; Lin, Wenping

doi:10.3389/fncel.2017.00391

Cited by 40 publications

(23 citation statements)

References 43 publications

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“…This short note combines, (A) the 2015 and 2016 observations of Basiorka et al ( 14 , 15 ) and 2016 work of Sallman ( 16 )—all three reporting that NLRP3 inflammasome constitutes a final common effector node driving a core element of the pathophysiology of MDS with, (B) the 2017 data sets of Ahn et al ( 26 ) and of Lin et al ( 27 ) plus the 2018 report of Hao et al ( 28 )—all three reporting that the NLRP3 inflammasome can be inhibited by the century old drug MB.…”

Section: Discussionmentioning

confidence: 88%

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Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in Myelodysplasia

Kast¹

2018

Front. Oncol.

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Myelodysplasia refers to a group of clonal hematopoietic neoplasms characterized by genetic heterogeneity, different clinical behaviors and prognoses. Some of this group of bone marrow failure conditions have known external causes, some are of unknown origin. Within marrow, intracellular, and extracellular elements of the innate immune system are activated and contribute to creation of multiple cytogenetic abnormalities and are central to the mode of hematopoietic cell failure. Basiorka et al. showed that NLRP3 inflammasome activity is essential to the innate immune system's destruction of marrow hematopoietic cells commonly in myelodysplasia. In April 2018 Hao et al. reported that methylene blue inhibits rat NLRP3 inflammasome function. Methylene blue has been in continuous use in humans for over a century. It is associated with an eminently benign side effect profile in human use. If as in rodents, methylene blue also inhibits NLRP3 inflammasome function in human myelodysplasia a trial of adjunctive methylene blue treatment in transfusion dependent, low risk myelodysplasia where marrow inflammation and apoptosis predominates, would be worth trying.HIGHLIGHTS - Cytogenetic abnormalities and innate immune activation are seen in myelodysplasia- The NLRP3 inflammasome is a core element generating marrow failure of myelodysplasia- In April 2018 methylene blue was reported to potently inhibit NLRP3 inflammasome function- Methylene blue has benign side effects and has been in human use for a century- Study of methylene blue treatment of myelodysplasia would be a low-risk intervention

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Section: Discussionmentioning

confidence: 88%

“…Ahn et al showed that MB inhibited LPS stimulated increase in murine NLRP3 function ( 26 ). Lin et al showed that MB inhibited murine cord transection initiated NLRP3 activation ( 27 ). Hao et al showed that MB inhibited NLRP3 assembly and function in streptozocin murine model of diabetic retinopathy ( 28 ).…”

Section: Methylene Bluementioning

confidence: 99%

Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in Myelodysplasia

Kast¹

2018

Front. Oncol.

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“…4). 23,33,35,37 These results, together with the fact that dark-rearing significantly slows the rate of central rod loss compared to cyclic light-rearing in C57BL/6J Pde6brd10 mice, further support the possibility that distinct mechanisms are responsible for rod degenera- Further analysis finds that the difference between mice fed normal chow versus N5MB chow was significant between male and female P50 dark-reared Pde6brd10 mice (horizontal line); in male mice this difference was not statistically distinguishable from zero, whereas it was in female mice (star). Together, these results show that the greatest impact on rod survival by N5MB chow is found in P50 darkreared female Pde6brd10 mice.…”

Section: Discussionmentioning

confidence: 99%

“…[28][29][30][31] MB has also demonstrated anti-inflammatory properties. 32,33 In addition, we tested Norgestrel, a synthetic progesterone, due to its ability to protect rods and cones from degeneration in cyclic light-reared Pde6brd10 mice, and its anti-oxidant and antiinflammatory properties. 23,[34][35][36][37][38][39]…”

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confidence: 99%

Rod Photoreceptor Neuroprotection in Dark-RearedPde6brd10Mice

Berkowitz

Podolsky

Childers

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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The purpose of this study was to test the hypothesis that anti-oxidant and / or anti-inflammation drugs that suppress rod death in cyclic light-reared Pde6brd10 mice are also effective in dark-reared Pde6brd10 mice. METHODS. In untreated dark-reared Pde6brd10 mice at post-natal (P) days 23 to 24, we measured the outer nuclear layer (ONL) thickness (histology) and dark-light thickness difference in external limiting membrane-retinal pigment epithelium (ELM-RPE) (optical coherence tomography [OCT]), retina layer oxidative stress (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]); and microglia/macrophage-driven inflammation (immunohistology). In dark-reared P50 Pde6brd10 mice, ONL thickness was measured (OCT) in groups given normal chow or chow admixed with methylene blue (MB) + Norgestrel (anti-oxidant, anti-inflammatory), or MB or Norgestrel separately. RESULTS. P24 Pde6brd10 mice showed no significant dark-light ELM-RPE response in superior and inferior retina consistent with high cGMP levels. Norgestrel did not significantly suppress the oxidative stress of Pde6brd10 mice that is only found in superior central outer retina of males at P23. Overt rod degeneration with microglia/macrophage activation was observed but only in the far peripheral superior retina in male and female P23 Pde6brd10 mice. Significant rod protection was measured in female P50 Pde6brd10 mice given 5 mg/kg/day MB + Norgestrel diet; no significant benefit was seen with MB chow or Norgestrel chow alone, nor in similarly treated male mice. CONCLUSIONS. In early rod degeneration in dark-reared Pde6brd10 mice, little evidence is found in central retina for spatial associations among biomarkers of the PDE6B mutation, oxidative stress, and rod death; neuroprotection at P50 was limited to a combination of anti-oxidant/anti-inflammation treatment in a sex-specific manner.

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“…It also improves systemic vascular resistance and mean arterial pressure while decreases vasopressor requirements in septic shock [ 265 ]. It also demonstrates anti-inflammatory effects because it can inhibit NLRP3 inflammasome activation [ 266 ]. The drug is currently being tested in the context of COVID-19 in a few trials alone (NCT04376788; n = 15) or in combination with vitamin C and N -acetylcysteine (NCT04370288; n = 20).…”

Section: Miscellaneous Antiviral Agentsmentioning

confidence: 99%

Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

Al‐Horani

Kar

2020

Viruses

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The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.

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Methylene Blue Mitigates Acute Neuroinflammation after Spinal Cord Injury through Inhibiting NLRP3 Inflammasome Activation in Microglia

Cited by 40 publications

References 43 publications

Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in Myelodysplasia

Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in Myelodysplasia

Rod Photoreceptor Neuroprotection in Dark-RearedPde6brd10Mice

Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review

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