Activation of Nrf2 signaling by natural products-can it alleviate diabetes?

Matzinger, Manuel; Fischhuber, Katrin; Heiss, Elke H.

doi:10.1016/j.biotechadv.2017.12.015

Cited by 176 publications

(111 citation statements)

References 527 publications

(545 reference statements)

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“…and lpd-5 depleted animals were actually more sensitive to oxidative stress and lutein, which has been shown to activate Nrf2/skn-1 in mammals [83], neither affected this response, nor suppressed nuo-5 RNAi-mediated induction of gst-4 (a well-established skn-1 target in response to oxidative stress). Thus, although we cannot rule out context specific effects of skn-1-mediated induction of nlg-1, our findings indicate nlg-1 overexpression in this disease context has a actually a detrimental rather than a protective effect.…”

Section: Discussionmentioning

confidence: 92%

Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein inC. elegans

Maglioni

Schiavi

Melcher

et al. 2020

Preprint

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Complex I deficiency represents 30% of the pathogenetic causes of human mitochondrial associated diseases (HMAD), thus being the most frequent defect of mitochondrial energy metabolism. Therapeutic options for these devastating, life-threating disorders, which in most cases present with neurodevelopmental defects, do not exist, in part due to the scarcity of appropriate model systems to study them. Caenorhabditis elegans is a powerful, genetically tractable model organism widely used to investigate neuronal development and degeneration.Here, we generated new C. elegans models for HMAD, which closely recapitulated the human pathologies, and we focused on two complex I disease models associated with Leigh Syndrome, nuo-5/NDUFS1-and lpd-5/NDUFS4-depleted animals, which were exploited for a suppressor screening. We identified lutein, among a library of natural compounds, for its ability to rescue the developmental arrest and neuronal deficits in the two models. Specifically, we found that lutein exerts its beneficial activity through suppression of a synaptic defect we disclosed for the first time upon nuo-5/NDUFS1 depletion, thus pointing to possible novel therapeutic targets for the human disease. 2 Abbreviations

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Section: Discussionmentioning

confidence: 92%

Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein inC. elegans

Maglioni

Schiavi

Melcher

et al. 2020

Preprint

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“…In addition to Atox1 and Mt1, the RNA‐Seq data also revealed significant upregulation of several genes in the Nrf2‐mediated signaling pathway, a major mechanism in the cellular defense against oxidative stress in CDM conditions. Some of those genes such as Sod1 (superoxide dismutase 1) and Prdx1 (peroxiredoxin 1) can directly detoxify ROS and H 2 O 2 while others such as GSTP (glutathione S‐transferase), Mgst3 (microsomal glutathione S‐transferase 3), and Txn (thioredoxin) may play roles in controlling ROS through changing glutathione levels.…”

Section: Discussionmentioning

confidence: 98%

Elucidating the Impact of CHO Cell Culture Media on Tryptophan Oxidation of a Monoclonal Antibody Through Gene Expression Analyses

Desai

Gao

et al. 2018

Biotechnology Journal

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Oxidation of monoclonal antibodies (mAb) is a common chemical modification with potential impact on a therapeutic protein's activity and immunogenicity. In a previous study, it was found that tryptophan oxidation (Trp-ox) levels of two mAb produced in Chinese hamster ovary (CHO) cells were significantly lowered by modifying cell culture medium/feed. In this study, transcriptome analysis by RNA-Seq is applied to further elucidate the underlying mechanism of those changes in lowering the Trp-ox levels. Cell samples from the 5L fed-batch conditions are harvested and subjected to RNA-Seq analysis. The results showed that the cell culture changes had little impact on neither the expression of the mAb transgenes nor genes related to glycosylation. However, those changes did significantly alter the expression of multiple genes (p-value ≤0.05 and absolute fold change ≥1.5 or adjusted p-value ≤0.1) involved in transport of copper, regulation of glutathione, iron storage, heme reduction, oxidative phosphorylation, and Nrf2-mediated antioxidative response. These findings suggest a key underlying mechanism in lowering Trp-ox levels by CDM was likely to be collectively controlling ROS levels through regulation of those genes' expression. This is the first example, to our knowledge, applying transcriptomic analysis to mechanistically understand the impact of cell culture on mAb oxidation.

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“…Further analysis of the biosynthetic site of bile acids and the liver confirmed that the conjugated bile acid TUDCA was generated in the liver through a series of catalytic reactions and enzymes such as CYP7A1 and BAAT. CYP7A1 is a rate-limiting enzyme that catalyzes the breakdown of cholesterol into bile acids in the liver 15,61 whereas BAAT is a vital enzyme that catalyzes the amidation reaction of taurine and UDCA 46,62 . Interestingly, we found that the gene expressions of Cyp7a1 and Baat were significantly enhanced in the HFD + Met group, which might further promote the synthesis of TUDCA in the liver.…”

Section: Discussionmentioning

confidence: 99%

Metformin increases tauroursodeoxycholic acid levels to improve insulin resistance in diet-induced obese mice

Zhang

Zuo

Yan

et al. 2020

Preprint

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16Metformin is widely used to surmount insulin resistance (IR) and diabetes. 17 Evidence indicates that metformin remodels gut microbiota but the underlying 18 mechanism remain unclear. Present results showed that metformin effectively 19 improved insulin sensitivity and alleviated liver inflammation and oxidative stress in 20 30 improves metabolism. 31 NRF2 33 34 35The prevalence of obesity and overweight have been on the rise worldwide 1,2 . 36 Current predictions indicate that more than 1 billion people will be obese by 2030 3 . 37 Visceral obesity precedes the development of metabolic complications and chronic 38 diseases such as type 2 diabetes (T2D) 4 , hepatic steatosis 5 and cardiovascular 39 diseases 6 . Metformin has been the first-line anti-diabetic drug for more than 60 years 40 because of its excellent hypoglycemic effect and safety profile 1,7 . Although several 41 studies have explored the mechanisms by which metformin maintains glucose 42 homeostasis, findings from such studies are inconsistent. The prevailing view is that 43 metformin activates AMP-activated protein kinase (AMPK) in the liver, similar to the 44 principle of caloric restriction that relieves symptoms of diabetes 8,9 . However, 45 metformin is an orally administered drug that reaches high concentrations in the 46 intestine with much lower serum concentrations 10 , thus, the possibility that its 47 metabolic therapeutic mechanism might be due in part to actions in the intestine 48 cannot be ignored. Accumulated evidence shows that a high-fat diet (HFD) reduces 49 the abundance of Lactobacilli in the small intestine. However, this can be 50 counteracted by metformin, which increases the proportion of probiotics, thus, 51 relieving the symptoms of HFD-induced diabetes 11 . Although metformin may play a 52 hypoglycemic effect by improving the gut microbiota, oral administration of 53 antibiotics to diabetic mice impairs the hypoglycemic ability of metformin 12 . In 54 addition, while metformin can increase the abundance of Escherichia coli, it can as 55 well reduce the abundance of Intestinibacter. This can further influence diverse 56 biological processes such as the synthesis of branched-chain amino acid and the 57 secretion of GPL-1, thereby improving glucose tolerance and alleviating insulin 58 resistance (IR) 13,14 . These findings suggest that modulation of gut microbiota is 59 involved in the hypoglycemic mechanism of metformin. 60 Bile acids (BAs), which are produced in the liver and serve as important 61 ingredients of the digestive fluid in the intestine, enter the small intestine through the 62 biliary system and participate in fat digestion and absorption 15,16 . Gathered evidence 63 demonstrates that BAs could improve the intestinal homeostasis by modulating the 64 gut microbiota, thus relieving metabolic syndrome 17 . Recent studies also suggest that 65 BAs can participate in the liver-gut axis circulation and the improvement of 66 HFD-initiated metabolic disorders by inhibiting the proliferation of path...

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Activation of Nrf2 signaling by natural products-can it alleviate diabetes?

Cited by 176 publications

References 527 publications

Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein inC. elegans

Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein inC. elegans

Elucidating the Impact of CHO Cell Culture Media on Tryptophan Oxidation of a Monoclonal Antibody Through Gene Expression Analyses

Metformin increases tauroursodeoxycholic acid levels to improve insulin resistance in diet-induced obese mice

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