scholarly journals SUN-LB101 NRF2 Represses Obesity-Associated Adipose Tissue Inflammation in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yoko Yagishita ◽  
Akira Uruno ◽  
Thomas W Kensler ◽  
Masayuki Yamamoto
Keyword(s):  
Adipose Tissue ◽  
Myeloid Cell ◽  
Potential Effect ◽  
Luciferase Reporter ◽  
Standard Diet ◽  
Related Factor ◽  
Nrf2 Pathway ◽  
Pathway Activation ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory

Abstract Obesity is associated with type 2 diabetes, cardiovascular disease and increased incidence of cancer. Chronic inflammation, mainly emanating from adipose tissue, has been proposed to be one of the links between obesity and these pathologies. Thus, identification of new targets against obesity and especially obesity-induced inflammation is needed urgently. Transcription factor Nrf2 (NF-E2-related-factor-2) plays a central role in cytoprotective responses to oxidative and electrophilic stresses and also exerts anti-inflammatory effects in rodent models of inflammation. However, whether activation of Nrf2 signaling pathway influences obesity-associated inflammation in adipose tissue is not well established. To this end, we generated mice with systemic activation of the Nrf2 pathway (Keap1flox/–), as well as mouse models with tissue-specific Nrf2 pathway activation: adipocyte-specific (Fabp4Cre::Keap1flox/ flox) and myeloid cell-specific (LymCre::Keap1flox/ flox). These mice were exposed to a high-fat diet (HFD) 60% kcal fat regimen for 6-weeks or crossed into the db/db background. Keap1flox/– mice showed a dramatic decrease of the numbers of F4/80-positive macrophages in white adipose tissue (WAT). Interestingly, both Fabp4Cre::Keap1flox/ flox and LymCre::Keap1flox/ flox mice showed suppression of F4/80-positive macrophages in WAT as well, suggesting enhanced Nrf2 signaling in either adipocytes or myeloid cells might contribute to anti-inflammatory effects in WAT under the stress of HFD. Transcript levels of inflammatory markers, especially macrophage F4/80 and Cd68 and the chemokine Ccl2 were decreased in the WAT from Keap1flox/– mice on the standard diet and also in the WAT of Keap1flox/– mice in the db/db background. Pharmacological activation of the Nrf2 pathway by treatment with CDDO-Im also suppressed Ccl2 expression in WAT of HFD fed mice and db/db mice. As CCL2 is a key mediator of macrophage accumulation in adipose tissue, we further studied the potential effect of Nrf2 on the transcriptional regulation of Ccl2 using 3T3-L1 preadipocyte and RAW264.7 macrophage cell lines. Treatment of both lines with the small molecule inducer of Nrf2, diethyl maleate significantly suppressed LPS-induced expression of Ccl2. Analysis using luciferase reporter assay revealed that a Nrf2 binding site in the Ccl2 5’ flanking region from -235 to +85 contributed to gene silencing of Ccl2 by activation of Nrf2. Our findings suggest that the druggable Nrf2 pathway may be an effective target to combat obesity-associated inflammation in adipose tissue and its’ concomitant metabolic disorders. Supported by AMED BINDS JP19am0101001 (MY), 19H05649 (MY), 16KK0195 (AU), NIH R35 CA197222 (TWK), JSPS OT 290125 (YY).

Sodium tanshinone IIA sulfate protects myocardium against paraquat-induced toxicity through activating the Nrf2 signaling pathway in rats

2018 ◽  
Vol 38 (2) ◽  
pp. 247-254 ◽  
Author(s):  
WX Zhang ◽  
XY Xiao ◽  
CG Peng ◽  
WL Chen ◽  
S Xie ◽  
...  
Keyword(s):  
Tanshinone Iia ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Intragastric Administration ◽  
Related Factor ◽  
Dependent Manner ◽  
Myocardial Cells ◽  
Sprague Dawley ◽  
Nrf2 Pathway ◽  
Nrf2 Signaling Pathway

Objective: To investigate the therapeutic effect and mechanism of sodium tanshinone IIA sulfate (STS) on paraquat (PQ)-induced myocardial injuries in a rat model. Methods: Healthy adult Sprague Dawley rats were randomly divided into normal control, PQ, and PQ + STS groups. PQ group was given a single intragastric administration of PQ (80 mg/kg). PQ + STS group was intraperitoneally injected with STS (1 ml/kg) at 30 min following PQ exposure. Rats in control and PQ groups were injected with equal amount of saline. After 12, 24, 48, and 72 h, rats were killed, and the apoptosis of myocardial cells was detected. Myocardial expression of Bax and Bcl-2 was measured. The activity of the nuclear erythroid 2-related factor 2 (Nrf2) pathway was assessed by Western blot. Results: The apoptotic cells in PQ group were significantly increased in a time-dependent manner compared with the control group ( p < 0.01). The rats in PQ group exhibited significantly lower Bcl-2 expression, but notably higher Bax expression at 12, 24, 48, and 72 h after PQ exposure ( p < 0.05 or 0.01). STS intervention markedly reduced the proportion of apoptotic myocardial cells, increased Bcl-2 expression, and decreased Bax expression at 24, 48, and 72 h after treatment ( p < 0.05 or 0.01). The expression of phosphorylated Nrf2 and heme oxygenase 1 in PQ + STS group was significantly increased compared with PQ and control groups ( p < 0.05 or 0.01). Conclusion: STS effectively inhibits PQ-induced myocardial cell apoptosis in rats via modulating the Nrf2 pathway, suggesting its potential as a promising therapeutic agent for PQ-induced myocardium damage.

scholarly journals Nuclear Factor Erythroid 2 Related Factor 2 Activator JC-5411 Inhibits Atherosclerosis Through Suppression of Inflammation and Regulation of Lipid Metabolism

2020 ◽  
Vol 11 ◽  
Author(s):  
Xinhai Jiang ◽  
Yining Li ◽  
Weizhi Wang ◽  
Xiaowan Han ◽  
Jiangxue Han ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Nuclear Factor ◽  
Phenethyl Isothiocyanate ◽  
Aortic Sinus ◽  
Anti Inflammatory

Phenethyl isothiocyanate is widely present in cruciferous vegetables with multiple biological effects. Here we reported the antiatherogenic effects and the underlying mechanisms of JC-5411 (Phenethyl isothiocyanate formulation) in vitro and in vivo. Luciferase reporter assay showed that JC-5411 increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE). JC-5411 treatment significantly increased the protein expression of Nrf2 and its downstream target gene hemeoxygenase 1 (HO-1) in liver of apolipoprotein E deficient (ApoE−/−) mice. Importantly, JC-5411 treatment significantly reduced atherosclerotic plaque area in both en face aorta and aortic sinus when compared with model group in WD induced ApoE−/− mice. JC-5411 obviously decreased proinflammatory factors’ levels in serum of ApoE−/− mice, LPS stimulated macrophages and TNFα induced endothelial cells, respectively. JC-5411 significantly decreased the levels of total cholesterol (TC) and triglyceride (TG) in both serum and liver of ApoE−/− mice and hyperlipidemic golden hamsters. Mechanism studies showed that JC-5411 exerted anti-inflammatory effect through activating Nrf2 signaling and inhibiting NF-κB and NLRP3 inflammasome pathway. JC-5411 exerted regulating lipid metabolism effect through increasing cholesterol transfer proteins (ABCA1 and LDLR) expression, regulating fatty acids synthesis related genes (p-ACC, SCD1 and FAS), and increasing fatty acids β-oxidation (CPT1A) in vivo. Furthermore, JC-5411 treatment had a favorable antioxidant effect in ApoE−/− mice by increasing the antioxidant related genes expression. Taken together, we conclude that JC-5411 as a Nrf2 activator has anti-inflammatory, rebalancing lipid metabolism, and antioxidant effects, which makes it as a potential therapeutic agent against atherosclerosis.

scholarly journals Tart Cherry Reduces Inflammation in Adipose Tissue of Zucker Fatty Rats and Cultured 3T3-L1 Adipocytes

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1576 ◽  
Author(s):  
Shasika Jayarathne ◽  
April Stull ◽  
Alexandra Miranda ◽  
Shane Scoggin ◽  
Kate Claycombe-Larson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Related Factor ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Adipose Tissue Inflammation ◽  
Tart Cherry ◽  
Tissue Inflammation ◽  
Anti Inflammatory

Obesity increases adipose tissue inflammation and secretion of pro-inflammatory adipokines, which have systemic effects on the organism’s health status. Our objective was to dissect mechanisms of anti-inflammatory effects of tart cherry (TC) in adipose tissue of Zucker fatty rats, and cultured 3T3-L1 adipocytes. Rats were fed either a control diet, or 4% TC powder diets for eight weeks. Body and epididymal fat pad weights were not significantly different between control and TC groups. However, rats fed the TC diet had significantly reduced adipose tissue inflammation (p < 0.05), as determined by reduced mRNA levels of pro-inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and CD-11b, and increased mRNA levels of type-1 arginase (Arg-1) anti-inflammatory marker. Consistent with these in vivo results, TC significantly decreased expression of IL-6 mRNA and protein levels in lipopolysaccharide (LPS) stimulated adipocytes compared to those stimulated with LPS, but no TC. Moreover, both in vivo (rat adipose tissue) and in vitro (3T3-L1 adipocytes), phosphorylation of p65-NF-κB subunit was significantly reduced by TC. Additionally, TC decreased mRNA expression of fatty acid synthase (FASN), and increased expression of peroxisome proliferator-activated receptor alpha (PPARα), master regulator of lipid oxidation, and anti-oxidant markers nuclear factor erythroid-derived 2-related factor (NRFs) in both models. In conclusion, our findings indicate that TC downregulates inflammation in part via the nuclear factor kappa B (NF-κB) pathway in adipose tissue. Thus, TC may serve as a potential intervention to reduce obesity-associated inflammation.

scholarly journals Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 167
Author(s):  
Seyed Hossein Shahcheraghi ◽  
Fateme Salemi ◽  
Niloufar Peirovi ◽  
Jamshid Ayatollahi ◽  
Waqas Alam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Glutamate Cysteine Ligase ◽  
Response Elements ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Molecular Aspects

Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc–curcumin Zn (II)–curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc–curcumin Zn (II)–curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.

scholarly journals Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Wen Ye ◽  
Chenlei Zheng ◽  
Dinglai Yu ◽  
Fan Zhang ◽  
Reguang Pan ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Inflammatory Factor ◽  
Lipoxin A4 ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory

Acute lung injury (ALI) is a critical event involved in the pathophysiological process of acute pancreatitis (AP). Many methods have been widely used for the treatment of AP-ALI, but few are useful during early inflammation. Lipoxin A4 (LXA4), a potent available anti-inflammatory and novel antioxidant mediator, has been extensively studied in AP-ALI, but its underlying mechanism as a protective mediator is not clear. This research was conducted to identify the possible targets and mechanisms involved in the anti-AP-ALI effect of LXA4. First, we confirmed that LXA4 strongly inhibited AP-ALI in mice. Next, using ELISA, PCR, and fluorescence detection to evaluate different parameters, LXA4 was shown to reduce the inflammatory cytokine production induced by AP and block reactive oxygen species (ROS) generation in vivo and in vitro. In addition, TNF-α treatment activated the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream gene heme oxygenase-1 (HO-1) in human pulmonary microvascular endothelial cells (HPMECs), and LXA4 further promoted their expression. This study also provided evidence that LXA4 phosphorylates Ser40 and triggers its nuclear translocation to activate Nrf2. Moreover, when Nrf2-knockout (Nrf2-/-) mice and cells were used to further assess the effect of the Nrf2/HO-1 pathway, we found that Nrf2 expression knockdown partially eliminated the effect of LXA4 on the reductions in inflammatory factor levels while abrogating the inhibitory effect of LXA4 on the ROS generation stimulated by AP-ALI. Overall, LXA4 attenuated the resolution of AP-induced inflammation and ROS generation to mitigate ALI, perhaps by modulating the Nrf2/HO-1 pathway. These findings have laid a foundation for the treatment of AP-ALI.

scholarly journals Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia

2011 ◽  
Vol 300 (4) ◽  
pp. H1133-H1140 ◽  
Author(s):  
Zoltan Ungvari ◽  
Lora Bailey-Downs ◽  
Tripti Gautam ◽  
Rosario Jimenez ◽  
Gyorgy Losonczy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
High Glucose ◽  
Target Genes ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Standard Diet ◽  
Related Factor ◽  
Antioxidant Genes ◽  
Gene Assay

Hyperglycemia in diabetes mellitus promotes oxidative stress in endothelial cells, which contributes to development of cardiovascular diseases. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor activated by oxidative stress that regulates expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes. This study was designed to elucidate the homeostatic role of adaptive induction of Nrf2-driven free radical detoxification mechanisms in endothelial protection under diabetic conditions. Using a Nrf2/antioxidant response element (ARE)-driven luciferase reporter gene assay we found that in a cultured coronary arterial endothelial cell model hyperglycemia (10–30 mmol/l glucose) significantly increases transcriptional activity of Nrf2 and upregulates the expression of the Nrf2 target genes NQO1, GCLC, and HMOX1. These effects of high glucose were significantly attenuated by small interfering RNA (siRNA) downregulation of Nrf2 or overexpression of Keap-1, which inactivates Nrf2. High-glucose-induced upregulation of NQO1, GCLC, and HMOX1 was also prevented by pretreatment with polyethylene glycol (PEG)-catalase or N-acetylcysteine, whereas administration of H2O2 mimicked the effect of high glucose. To test the effects of metabolic stress in vivo, Nrf2+/+ and Nrf2−/− mice were fed a high-fat diet (HFD). HFD elicited significant increases in mRNA expression of Gclc and Hmox1 in aortas of Nrf2+/+ mice, but not Nrf2−/− mice, compared with respective standard diet-fed control mice. Additionally, HFD-induced increases in vascular ROS levels were significantly greater in Nrf2−/− than Nrf2+/+ mice. HFD-induced endothelial dysfunction was more severe in Nrf2−/− mice, as shown by the significantly diminished acetylcholine-induced relaxation of aorta of these animals compared with HFD-fed Nrf2+/+ mice. Our results suggest that adaptive activation of the Nrf2/ARE pathway confers endothelial protection under diabetic conditions.

scholarly journals Toll-Like Receptor Signaling Induces Nrf2 Pathway Activation through p62-Triggered Keap1 Degradation

2015 ◽  
Vol 35 (15) ◽  
pp. 2673-2683 ◽  
Author(s):  
Shasha Yin ◽  
Wangsen Cao
Keyword(s):  
Target Genes ◽  
Critical Event ◽  
Toll Like Receptor ◽  
Microbial Infection ◽  
Tlr Signaling ◽  
Nrf2 Pathway ◽  
Tlr Agonists ◽  
Pathway Activation ◽  
Nrf2 Activation ◽  
Nrf2 Signaling Pathway

Toll-like receptors (TLRs) induce inflammation and tissue repair through multiple signaling pathways. The Nrf2 pathway plays a key role in defending against the tissue damage incurred by microbial infection or inflammation-associated diseases. The critical event that mediates TLR-induced Nrf2 activation is still poorly understood. In this study, we found that lipopolysaccharide (LPS) and other Toll-like receptor (TLR) agonists activate Nrf2 signaling and the activation is due to the reduction of Keap1, the key Nrf2 inhibitor. TLR signaling-induced Keap1 reduction promoted Nrf2 translocation from the cytoplasm to the nucleus, where it activated transcription of its target genes. TLR agonists modulated Keap1 at the protein posttranslation level through autophagy. TLR signaling increased the expression of autophagy protein p62 and LC3-II and induced their association with Keap1 in the autophagosome-like structures. We also characterized the interaction between p62 and Keap1 and found that p62 is indispensable for TLR-mediated Keap1 reduction: TLR signaling had no effect on Keap1 if cells lacked p62 or if cells expressed a mutant Keap1 that could not interact with p62. Our study indicates that p62-mediated Keap1 degradation through autophagy represents a critical linkage for TLR signaling regulation of the major defense network, the Nrf2 signaling pathway.

scholarly journals Dandelion Extract Alleviated Lipopolysaccharide-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 496 ◽  
Author(s):  
Yawang Sun ◽  
Yongjiang Wu ◽  
Zili Wang ◽  
Juncai Chen ◽  
You Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Cell Line ◽  
Related Factor ◽  
Nrf2 Pathway ◽  
Bovine Mammary Epithelial Cells ◽  
Nrf2 Signaling Pathway

In practical dairy production, cows are frequently subjected to inflammatory diseases, such as high-grain diet-induced subacute ruminal acidosis (SARA) as well as mastitis and metritis. Under the circumstances, lipopolysaccharide (LPS) induces oxidative stress within the cow and in the mammary epithelial cells. It has implications in practical production to alleviate oxidative stress and to optimize the lactational function of the mammary epithelial cells. This study thus aimed to investigate the antioxidative effects of dandelion aqueous extract (DAE) on LPS-induced oxidative stress and the mechanism of DAE as an antioxidant to alleviate oxidative stress through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the bovine mammary epithelial cell line MAC-T cells. The cells were cultured for 48 h in six treatments including control (without LPS and DAE), LPS (100 ng/mL), DAE10 (100 ng/mL LPS and 10 μg/mL DAE), DAE50 (100 ng/mL LPS and 50 μg/mL DAE), DAE100 (100 ng/mL LPS and 100 μg/mL DAE), and DAE200 (100 ng/mL LPS and 200 μg/mL DAE), respectively. The results showed that cell viability was reduced by LPS, and the adverse effect of LPS was suppressed with the supplementation of DAE. Lipopolysaccharide-induced oxidative stress through enhancing reactive oxygen species (ROS) production, resulted in increases in oxidative damage marker concentrations, while 10 and 50 μg/mL DAE alleviated the LPS-induced oxidative stress via scavenging cellular ROS and improving antioxidant enzyme activity. The upregulation of antioxidative gene expression in DAE treatments was promoted through activating the Nrf2 signaling pathway, with DAE at a concentration of 50 μg/mL exhibiting the highest effect. Overall, DAE acted as an effective antioxidant to inhibit LPS-induced oxidative stress and as a potential inducer of the Nrf2 signaling pathway.

scholarly journals Schisandrin B Attenuates Airway Inflammation by Regulating the NF-κB/Nrf2 Signaling Pathway in Mouse Models of Asthma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yaqin Chen ◽  
Yu Kong ◽  
Qili Wang ◽  
Jian Chen ◽  
Hua Chen ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Signaling Pathway ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Responses ◽  
Related Factor ◽  
Inflammatory Disorder ◽  
Schisandrin B ◽  
Traditional Chinese Herbal Medicine ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory

Background. Asthma is a complex inflammatory disorder that plagues a large number of people. Schisandrin B is an active ingredient of the traditional Chinese herbal medicine Schisandra with various proven physiological activities such as anti-inflammatory and antioxidant activities. In this study, we explored the anti-inflammatory and antioxidant effects and provided the mechanistic insights into the activity of schisandrin B in a mouse model of ovalbumin- (OVA-) induced allergic asthma. Methods. Male BALB/c mice were sensitized and challenged with OVA to induce asthma and treated with various doses (15 mg/kg, 30 mg/kg, and 60 mg/kg) of SCH to alleviate the features of allergic asthma, airway hyperresponsiveness, inflammatory response, OVA-specific immunoglobulin (Ig)E level, and pathological injury. Results. Schisandrin B significantly attenuated the airway hyperresponsiveness induced by OVA. Moreover, schisandrin B administration suppressed inflammatory responses, reduced the level of IgE, and attenuated pathological injury. Mechanistically, schisandrin B treatment promoted the activation of nuclear erythroid 2-related factor 2 (Nrf2), but suppressed the stimulation of the NF-κB pathway caused by OVA. Conclusion. Taken together, our study suggests that schisandrin B attenuates the features of asthmatic lungs by inhibiting the NF-κB pathway and activating the Nrf2 signaling pathway.

scholarly journals Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Temidayo D. Popoola ◽  
Stephanie T. Guetchueng ◽  
Kenneth J. Ritchie ◽  
Olufunsho Awodele ◽  
Nicola M. Dempster ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Chemical Constituents ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Root Extract ◽  
Related Factor ◽  
Nitric Oxide Release ◽  
Anti Cancer ◽  
Fold Induction ◽  
Anti Inflammatory

Abstract Background Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. Methods Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2′,7′-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). Results Extracts up to 100 μg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 μg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. Conclusion As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.

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