Dimethyl Fumarate and Monomethyl Fumarate Promote Post-Ischemic Recovery in Mice

Yao, Yang; Miao, Weimin; Liu, Zhijia; Han, Wei; Shi, Kaibin; Shen, Yi; Li, Handong; Liu, Qiang; Fu, Ying; Huang, DeRen; Shi, Fu‐Dong

doi:10.1007/s12975-016-0496-0

Cited by 94 publications

(92 citation statements)

References 73 publications

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“…Wu et al . reported that the Nrf2/ARE pathway activator myricetin lessened the production of ROS, decreased infarct volume, and reduced neuronal loss after ischemia (44, 45). This conclusion is supported by another study employing a second Nrf2/ARE pathway activator, Panax notoginseng saponins (46).…”

Section: The Neuroprotective Effects Of the Nrf2/are Pathway Againmentioning

confidence: 99%

Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases

Sun

Yang

Leak

et al. 2017

CNSNDDT

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Central nervous system diseases are major health issues and are often associated with disability or death. Most central nervous system disorders are characterized by high levels of oxidative stress. Nuclear factor erythroid 2 related factor (Nrf2) is known for its ability to regulate the expression of a series of enzymes with antioxidative, prosurvival, and detoxification effects. Under basal conditions, Nrf2 forms a complex with Kelch-like ECH associated protein 1, leading to Nrf2 inactivation via ubiquitination and degradation. However, following exposure of Keap1 to oxidative stress, Nrf2 is released from Keap1, activated, and translocated into the nucleus. Upon nuclear entry, Nrf2 binds to antioxidant response elements (ARE), thereby inducing the expression of genes such as glutathione s-transferase, heme oxygenase 1, and NADPH quinine oxidoreductase 1. Many dietary phytochemicals have been reported to activate the protective Nrf2/ARE pathway. Here, we review the preventive and protective effects of dietary Nrf2 activators against CNS diseases, including stroke, traumatic brain injury, Alzheimer’s disease, and Parkinson’s disease.

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Section: The Neuroprotective Effects Of the Nrf2/are Pathway Againmentioning

confidence: 99%

Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases

Sun

Yang

Leak

et al. 2017

CNSNDDT

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“…Concomitantly, levels of pro-inflammatory cytokines were greatly reduced in the plasma and brain and oxygen-glucose deprived neuron/glia cultures. Further, using a mouse model of transient focal brain ischemia, Yao et al [92] showed that DMF and MMF (30 mg/kg i.p.) significantly reduced neurological deficits, infarct volume, brain edema, and cell death.…”

Section: Strokementioning

confidence: 99%

“…Additionally, DMF and MMF suppress glial activation following brain ischemia. Importantly, the protection of DMF and MMF was most evident during the sub-acute stage and was abolished in Nrf2 −/− mice, indicating that the Nrf2 pathway is required for the beneficial effects of DMF and MMF [92]. In another study, murine organotypic hippocampal slice cultures, and two neuronal cell lines were treated with DMF and MMF [93].…”

Section: Strokementioning

confidence: 99%

Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

Jadeja¹,

Powell²,

Martin³

2020

Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications

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The medicinal benefit of salts of fumaric acid and its esters (FAE), known as fumarates (mono and dimethyl fumarate), was realized many years ago. Early on, FAE were derived from plants and mushrooms (e.g., Fumaria officinalis, Boletus fomentarius var. pseudo-igniarius). The FAE containing formulation Fumaderm ® was licensed in Germany for the treatment of psoriasis in 1994. Recently, a clinical formulation of dimethyl fumarate known as BG12 (Tecfidera) was approved for use in the United States, New Zealand, Australia, European Union, Switzerland, and Canada for the treatment of multiple sclerosis. Others and we have assessed the potential benefit of FAE in a number of disease conditions that are diverse with respect to etiology but unified with regard to the involvement of inflammation and oxidative stress. Hence, a FAE-based drug with robust anti-oxidative and anti-inflammatory effects that is already US-FDA approved is a perfect contender for repurposing and rapid clinical implementation for their management. There is a burgeoning literature on the use of FAE in the prevention and treatment of diseases, other than psoriasis and MS, in which oxidative stress and/or inflammation are prominent. This chapter highlights critical information gleaned from these studies, exposes lacunae of potential importance, and provides related perspectives.Keywords: fumaric acid esters, oxidative stress, Nrf2, antioxidant Drug Repurposing Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation:… DOI: http://dx.doi.org/10.5772/intechopen.91915 in which oxidative stress and/or inflammation are prominent. The present review highlights critical information gleaned from these studies and exposes and provides perspectives on lacunae of potential importance. Pharmacokinetics of fumaric acid estersDimethyl fumarate (PubChem CID: 637568), described as a "white crystalline compound with a fruit-like taste" [19], is a dimethyl ester of fumaric acid with the official chemical name of trans-1,2-ethylene carboxylic acid dimethyl ester [20]. Because of its rapid degradation by intestinal esterase, DMF does not cross the intestinal wall in significant amounts [21]. Thus, because of its short-lived activity, evidence of direct, sustained anti-inflammatory or antioxidant effects derived directly from DMF is limited [22]. Instead, monomethyl fumarate (MMF; PubChem CID: 21721168), the product of DMF metabolism by intestinal esterase, is said to be the main active metabolite [23]. This is confirmed by pharmacokinetic studies that demonstrate following oral DMF intake, serum concentrations of MMF peak within 2-2.5 h and its half-life is approximately 1 h [24]. Further, the ingestion of DMF along with a high fat/high-calorie diet was found to interfere with intestinal absorption, delaying the systemic peak of MMF significantly [16,17]. Following doses of delayed-release DMF of up to 240 mg, the mean C max of MMF in healthy human subjects was 1.43 μg/ml with a corresponding MMF area under the curve of 2.41 μg h/ml. ...

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“…Since nonenzymatic substances (e.g., melatonin and ursolic acid) can detoxify ROS [62], and antioxidant enzymes (e.g., superoxide dismutase) and catalase (CAT) have effects on scavenging superoxide radicals; declined levels of those antioxidants negatively affect health in varying degrees [63,64]. Inhibition or lack of nuclear factor erythroid 2-related factor (Nrf2) which recognizes the antioxidant response element (ARE) and protects cells from ROS accumulation may increase injury to patients; however, this can be reversed by administration of antioxidants [65], such as dimethyl fumarate and monomethyl fumarate [66]. It is therefore not surprising that alterations in OS and anti-OS levels are found in ischemic CVD and depression as discussed earlier.…”

Section: Oxidative Stress and Antioxidativementioning

confidence: 99%

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

Lin

Wang

Yan

et al. 2019

Oxidative Medicine and Cellular Longevity

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The public health sector faces a huge challenge as a result of the high prevalence and burden of disability caused by ischemic cardio-cerebrovascular disease (CVD) and depression. Although studies have explored the underlying mechanisms and potential therapies to address conditions, there is no treatment breakthrough, especially for depression which is highly influenced by social stressors. However, accumulating evidence reveals that CVD and depression are correlated and share common risk factors, particularly obesity, diabetes, and hypertension. They also share common mechanisms, including oxidative stress (OS), inflammation and immune response, cell death signaling pathway, and microbiome-gut-brain axis. This review summarizes the relationship between ischemic CVD and depression and describes the interactions among common risk factors and mechanisms for these two diseases. In addition, we propose that OS mediates the crosstalk between these diseases. We also reveal the potential of antioxidants to ameliorate OS-related injuries.

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Dimethyl Fumarate and Monomethyl Fumarate Promote Post-Ischemic Recovery in Mice

Cited by 94 publications

References 73 publications

Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases

Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases

Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

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