NRF2 activator 
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  • ||||||||||  Journal:  Ribisins and Certain Analogues Exert Neuroprotective Effects through Activation of the Keap1-Nrf2-ARE Pathway. (Pubmed Central) -  Sep 30, 2022   
    In silico molecular modeling suggests that certain of the ribisins can dock in the Nrf2-binding Kelch domain in Keap1, while cysteine labeling by biotinylated iodoacetamide suggest that cysteine residues within Keap1 react with the ribisins. It is thus proposed that the most active compounds exert their neuroprotective activities by targeting Keap1, thereby activating Nrf2 and so increasing transactivation of Nrf2-responsive genes that encode for detoxifying and antioxidant enzymes.
  • ||||||||||  Journal:  Activated AMP-activated protein kinase prevents hepatic steatosis, oxidative stress and inflammation in primary chicken hepatocytes. (Pubmed Central) -  Sep 29, 2022   
    In addition, we found that the beneficial effects of AMP-activated protein kinase signal in relieving lipid metabolism disorders, oxidative stress and inflammatory response are achieved by activating the nuclear factor erythroid 2-related factor 2 (NRF-2)/kelch-like ECH-associated protein 1 (KEAP1) pathway and inhibiting the NF-κB pathway in PO-stimulated primary chicken hepatocytes. Collectively, our data demonstrated that AMP-activated protein kinase acts as a potential target for the prevention of fatty liver hemorrhagic syndrome occurrence in laying hens.
  • ||||||||||  Journal:  Isoginkgetin, a bioactive constituent from Ginkgo Biloba, protects against obesity-induced cardiomyopathy via enhancing Nrf2/ARE signaling. (Pubmed Central) -  Sep 29, 2022   
    Of note, the protective effects conferred by IGK against obesity-induced mitochondrial defects and cardiac dysfunction was compromised by Nrf2 gene silencing both in vitro and in vivo, consolidating a pivotal role of Nrf2 in IGK-elicited myocardial protection against MC. Thus, the present study identifies IGK as a promising drug candidate to alleviate obesity-induced oxidative stress and cardiomyocyte damage through Nrf2 activation, highlighting the therapeutic potential of IGK in ameliorating obesity-induced cardiomyopathy.
  • ||||||||||  Journal:  New phenolic glycosides from Anemone chinensis Bunge and their antioxidant activity. (Pubmed Central) -  Sep 29, 2022   
    Pulsatillanin A (1) demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.7 cells by reducing ROS production, enhancing antioxidant enzyme SOD activity, replenishing depleted GSH in a dose-dependent manner. Western blot analysis revealed that 1 showed antioxidant activity via activating Nrf2 signaling pathway.
  • ||||||||||  indomethacin / Generic mfg.
    Preclinical, Journal, IO biomarker:  Protective effect of Anwulignan on gastric injury induced by indomethacin in mice. (Pubmed Central) -  Sep 29, 2022   
    Therefore, AN has a significant protection against the indomethacin-induced gastric injury in mice,the mechanism may be concerned in its activation of Nrf2, inhibition of NF-κB signaling pathway, and anti-apoptotic effect. Significance Statement AN significantly reduced the indomethacin-induced gastric injury in mice, and this may be related to its anti-oxidation, anti-inflammation, and anti-apoptosis, suggesting that AN has a potential to be a drug or food supplement for gastric injury induced by indomethacin.
  • ||||||||||  oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
    Journal:  Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis. (Pubmed Central) -  Sep 28, 2022   
    Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1β...Animal experiments further confirmed the great cartilage-protecting ability of MSN-OL through upregulating the expression of Nrf2/HO-1 signaling pathway without obvious toxicity. In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy.
  • ||||||||||  Enrollment open:  Treatment Strategy to Enhance Nrf2 Signaling in Older Adults (clinicaltrials.gov) -  Sep 28, 2022   
    P=N/A,  N=30, Recruiting, 
    In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy. Not yet recruiting --> Recruiting
  • ||||||||||  colistin sulphate / Generic mfg.
    Journal:  An Encapsulated Organic Acid and Essential Oil Mixture Improves the Intestinal Health of Weaned Piglets by Altering Intestinal Inflammation and Antioxidative Capacity. (Pubmed Central) -  Sep 25, 2022   
    In total, 120 weaned piglets (23 days of age; 6.96 ± 0.08 kg) were randomly allotted to four treatments (six replicates/group; five piglets/replicate): the control group (CON) was fed the basal diet (BD), the antibiotic growth promoters group (AGP) received the BD with 20 mg/kg colistin sulphate and 10 mg/kg bacitracin zinc, and OAEO1 and OAEO2 were fed the BD with 1000 mg/kg and 2000 mg/kg OAEO, respectively...In addition, AGP increased ADG, serum IgA level and GPX activity, jejunal trypsin activity and IL-10 content and mRNA level (p < 0.05) compared with CON but reduced the serum TNF-α content and DAO activity and jejunal NF-κB mRNA level (p < 0.05). Overall, OAEO as an alternative to AGP improved the growth performance, immuno-antioxidant status and gut health of weaned piglets partly via activating the Nrf2 signaling pathway and suppressing the TLR4/NF-κB signaling pathway.
  • ||||||||||  Preclinical, Journal, IO biomarker:  NRF2 Mediates Cellular Resistance to Transformation, Radiation, and Inflammation in Mice. (Pubmed Central) -  Sep 25, 2022   
    Delayed NRF2 responses to IR may be critical for the immune transition from prooxidant inflammation to antioxidant healing as well as in driving cellular radioresistance and survival. Targeting NRF2 to reprogram immunity could be of considerable therapeutic benefit in radiation and immunotherapy.
  • ||||||||||  Journal:  Bacterial Metabolite Reuterin Attenuated LPS-Induced Oxidative Stress and Inflammation Response in HD11 Macrophages. (Pubmed Central) -  Sep 25, 2022   
    Additionally, it was found that both pretreatment and cotreatment with reuterin remarkably inhibited the oxidative stress induced by LPS stimulation by activating the Nrf2/HO-1 signaling pathway and enhancing the activities of antioxidative enzymes. These findings suggested the immunoregulatory function of reuterin and indicated this bacterial metabolite was able to inhibit the inflammation and oxidative stress of HD11 macrophages once exposed to LPS stimulation.
  • ||||||||||  Preclinical, Journal:  Camellia sinensis L. Alleviates Pulmonary Inflammation Induced by Porcine Pancreas Elastase and Cigarette Smoke Extract. (Pubmed Central) -  Sep 25, 2022   
    In particular, the CLE suppressed the release of cytokines and chemokines caused by activating the nuclear factor kappa-light-chain-enhancer of activated B via the activation of nuclear factor erythroid-2-related factor 2 and the heme oxygenase-1 pathway in CSE/LPS-stimulated MH-S cells. Therefore, we suggest that the CLE administration be the effective approach for treating or preventing chronic pulmonary diseases such as COPD induced by CS.
  • ||||||||||  Review, Journal:  The Role of Nrf2 in Pulmonary Fibrosis: Molecular Mechanisms and Treatment Approaches. (Pubmed Central) -  Sep 25, 2022   
    Nrf2 orchestrates the activation of multiple protective genes that target inflammation, oxidative stress, fibroblast-myofibroblast differentiation (FMD), and epithelial-mesenchymal transition (EMT), and the mechanisms involve Nrf2 and its downstream antioxidant, Nrf2/HO-1/NQO1, Nrf2/NOX4, and Nrf2/GSH signaling pathway. We hope to indicate potential for Nrf2 system as a therapeutic target for pulmonary fibrosis.
  • ||||||||||  Journal:  Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte. (Pubmed Central) -  Sep 25, 2022   
    Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.
  • ||||||||||  Review, Journal:  Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson's Disease. (Pubmed Central) -  Sep 25, 2022   
    We propose that the transcriptional repressor of BTB and CNC homology 1 (Bach1), which antagonizes Nrf2, could serve as a promising complementary target for the activation of both Nrf2-dependent and Nrf2-independent neuroprotective pathways. This review presents the current knowledge on the Nrf2/Bach1 signaling pathway, its role in various cellular processes, and the benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 using non-electrophilic small molecules as a novel therapeutic approach for PD.
  • ||||||||||  azacitidine / Generic mfg., decitabine / Generic mfg.
    Journal:  HO/DEM-Promoted Maft Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish. (Pubmed Central) -  Sep 24, 2022   
    At last, antioxidant target genes were activated. It was shown that HO and DEM cooperated with methyltransferase inhibitors, providing an important reference for the treatment of oxidative stress-related diseases and breaking new ground for the study of the mechanism of methyltransferase inhibitors in the process of tumor chemotherapy.
  • ||||||||||  Journal:  The Case for Moxibustion for Painful Syndromes: History, principles and rationale. (Pubmed Central) -  Sep 24, 2022   
    There is ample scope for future study in this area and consideration of the history, development and practical applications of moxibustion therapy may be of help in this regard. This article seeks to explore the background, principles, and application of moxibustion in the clinical setting with particular emphasis on its potential for symptom management in the treatment of neuropathy and pain.
  • ||||||||||  Review, Journal:  Nutraceutical Prevention of Diabetic Complications-Focus on Dicarbonyl and Oxidative Stress. (Pubmed Central) -  Sep 24, 2022   
    Induction of glyoxalase I and metallothionein may explain the protective impact of zinc in rodent models of diabetic complications. With respect to the contribution of oxidative stress to diabetic complications, promoters of mitophagy and mitochondrial biogenesis, UCP2 inducers, inhibitors of NAPDH oxidase, recouplers of eNOS, glutathione precursors, membrane oxidant scavengers, Nrf2 activators, and correction of diabetic thiamine deficiency should help to quell this.
  • ||||||||||  Journal:  Geniposide Alleviates Oxidative Damage in Hepatocytes through Regulating miR-27b-3p/Nrf2 Axis. (Pubmed Central) -  Sep 24, 2022   
    Our findings indicated that GEN treatment recovered HO-induced oxidative stress via targeting miR-27b-3p and thereby enhanced the antioxidant capacity by stimulating nuclear translocation and accumulation of Nrf2. These findings suggest that inhibition of miR-27b-3p to activate the Nrf2/ARE pathway by GEN is a potential alternative for hepatic oxidative damage alleviation.
  • ||||||||||  Journal:  Basic fibroblast growth factor protects against liver ischemia-reperfusion injury via the Nrf2/Hippo signaling pathway. (Pubmed Central) -  Sep 24, 2022   
    bFGF activated Nrf2 to restrain the phosphorylation of promote Yes-associated protein (YAP) and YAP stabilization, thus reducing cell apoptosis and inflammation in ROS-dependent manner, revealed that Hippo signaling was the downstream of Nrf2 mediating protective effects of bFGF during hepatic IRI. In conclusion, our findings suggest that bFGF could reduce hepatic IRI and hepatocyte injury via the Nrf2/Hippo signaling pathway.
  • ||||||||||  Review, Journal:  Nrf2 and Oxidative Stress in liver Ischemia/Reperfusion Injury. (Pubmed Central) -  Sep 23, 2022   
    After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.