scholarly journals The Nrf2/HO-1 Axis as Targets for Flavanones: Neuroprotection by Pinocembrin, Naringenin, and Eriodictyol

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Solomon Habtemariam

Flavanones are a group of flavonoids that derive from their immediate chalcone precursors through the action of chalcone isomerase enzymes. The Aromatic A and B rings, C4-keto group, and the 15-carbon flavonoid skeleton are all evident in flavanones, but a notable absence of C2-C3 double bond and a lack of oxygenation at C-3 position of the C-ring makes them distinctively different from other groups such as flavonols (e.g., quercetin). On the basis of oxygenation level in the B ring, flavanones can vary from each other as exemplified by pinocembrin (no oxygenation), naringenin (4′-hydroxyl), or eriodictyol (3′,4′-dihydroxyl substitution). These groups are generally weaker free radical scavengers as compared to quercetin and derivatives though eriodictyol has a better free radical scavenging profile within the group due to the presence of the catechol functional moiety. In this communication, their antioxidant potential through the induction of antioxidant defenses is scrutinized. These compounds as exemplified by pinocembrin could induce the nuclear factor erythroid 2-related factor 2- (Nrf2-) heme oxygenase-1 (HO-1) axis leading to amelioration of oxidative stress in cellular and animal models. Their neuroprotective effect through such mechanism is discussed.

Foods ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1033 ◽  
Author(s):  
Yoonsu Kim ◽  
Jisun Oh ◽  
Chan Ho Jang ◽  
Ji Sun Lim ◽  
Jeong Soon Lee ◽  
...  

The fruit of Ziziphus jujuba, commonly called jujube, has long been consumed for its health benefits. The aim of this study was to examine the protective effect of dietary supplementation of enzymatically hydrolyzed jujube against lung inflammation in mice. The macerated flesh of jujube was extracted with aqueous ethanol before and after Viscozyme treatment. The extract of enzyme-treated jujube, called herein hydrolyzed jujube extract (HJE), contained higher levels of quercetin, total phenolics, and flavonoids, and exhibited more effective radical-scavenging abilities in comparison to non-hydrolyzed jujube extract (NHJE). HJE treatment decreased production of inflammation-associated molecules, including nitric oxide and pro-inflammatory cytokines from activated Raw 264.7 or differentiated THP-1 cells. HJE treatment also reduced expression of nuclear factor-κB and its downstream proteins in A549 human lung epithelial cells. Moreover, oral supplementation of 1.5 g of HJE per kg of body weight (BW) attenuated histological lung damage, decreased plasma cytokines, and inhibited expression of inflammatory proteins and oxidative stress mediators in the lungs of mice exposed to benzo(a)pyrene at 50 mg/kg BW. Expression levels of antioxidant and cytoprotective factors, such as nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1, were increased in lung and liver tissues from mice treated with HJE, compared to mice fed NHJE. These findings indicate that dietary HJE can reduce benzo(a)pyrene-induced lung inflammation by inhibiting cytokine release from macrophages and promoting antioxidant defenses in vivo.


2015 ◽  
Vol 10 (3) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Paulina Strugala ◽  
Anna Dudra ◽  
Alicja Z. Kucharska ◽  
Anna Sokół-Łętowska ◽  
Dorota Wojnicz ◽  
...  

In this study we focused on the chemical composition, antioxidant, anti-inflammatory and antibacterial properties of methanol and water extracts of fruits of six species grown in south-west Poland: blackberry, blackcurrant, chokeberry, cherry, gooseberry and raspberry. No general correlation could be drawn between extract chemical properties (i.e. antioxidant and free radical scavenging) and observed biological effects. However, blackcurrant and blackberry extracts (both methanol and water) appeared to be good antioxidants and free radical scavengers, as well as effective inhibitors of E. coli adhesion to the uroepithelial cells. On the other hand, the poorest antioxidants and free radical scavengers, cherry and gooseberry extracts, also poorly affected bacterial growth, swimming ability and adhesion to epithelial cells. Surprisingly, gooseberry extracts, which showed generally weak effects, appeared to be the most effective inhibitor of bacterial biofilm formation. Additionally, most of the studied extracts showed reasonably strong anti-inflammatory properties.


2005 ◽  
Vol 230 (7) ◽  
pp. 455-463 ◽  
Author(s):  
Gene C. Ness ◽  
Laura C. Pendleton ◽  
Michael J. McCreery

Several model systems were employed to assess indirect effects that occur in the process of using radiation inactivation analysis to determine protein target sizes. In the absence of free radical scavengers, such as mannitol and benzoic acid, protein functional unit sizes can be drastically overestimated. In the case of glutamate dehydrogenase, inclusion of free radical scavengers reduced the apparent target size from that of a hexamer to that of a trimer based on enzyme activity determinations. For glucose-6-phosphate dehydrogenase, the apparent target size was reduced from a dimer to a monomer. The target sizes for both glutamate dehydrogenase and glucose-6-phosphate dehydrogenase in the presence of free radical scavengers corresponded to subunit sizes when determinations of protein by sodium dodecyl sulfate–polyacrylamide gel electrophoresis or immunoblotting were done rather than enzyme activity. The free radical scavengers appear to compete with proteins for damage by secondary radiation products, since irradiation of these compounds can result in production of inhibitory species. Addition of benzoic acid/mannitol to samples undergoing irradiation was more effective in eliminating secondary damage than were 11 other potential free radical scavenging systems. Addition of a free radical scavenging system enables more accurate functional unit size determinations to be made using radiation inactivation analysis.


2020 ◽  
Vol 9 (4) ◽  
pp. 996
Author(s):  
Chih-Hsuan Hsia ◽  
Thanasekaran Jayakumar ◽  
Joen-Rong Sheu ◽  
Chih-Wei Hsia ◽  
Wei-Chieh Huang ◽  
...  

Activated microglia are crucial in the regulation of neuronal homeostasis and neuroinflammation. They also contribute to neuropathological processes after ischemic stroke. Thus, finding new approaches for reducing neuroinflammation has gained considerable attention. The metal ruthenium has gained notable attention because of its ability to form new complexes that can be used in disease treatment. [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), a potent ruthenium (II)-derived compound, was used in this study to investigate its neuroprotective action against microglia activation, middle cerebral artery occlusion (MCAO)-induced embolic stroke, and platelet activation, respectively. TQ-6 (2 μM) potently diminished inflammatory mediators (nitric oxide/inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)) expression, nuclear factor kappa B (NF-κB) p65 phosphorylation, nuclear translocation, and hydroxyl radical (OH•) formation in LPS-stimulated microglia. Conversely, TQ-6 increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Moreover, it significantly reduced brain infarct volume and edema in MCAO mice. Additionally, it drastically inhibited platelet aggregation and OH• production in mice platelets. This study confirmed that TQ-6 exerts an anti-neuroinflammatory effect on microglia activation through neuroprotection, antiplatelet activation, and free radical scavenging. The authors propose that TQ-6 might mitigate neurodegenerative pathology by inhibiting the NF-κB-mediated downstream pathway (iNOS and COX-2) and enhancing Nrf2/HO-1 signaling molecules in microglia.


2020 ◽  
Vol 17 (9) ◽  
pp. 1177-1185
Author(s):  
Rafaila Rafique ◽  
Arshia ◽  
Kanwal ◽  
Khalid Mohammed Khan ◽  
Sridevi Chigurupati ◽  
...  

Background: Free radicals are the main cause of numerous diseases. Their overproduction needs to be controlled in order to combat several ailments. The current study deals with the discovery of new free radical scavengers. Methods: Substituted N-hydrazinecarbothioamide indazoles 1-18 were evaluated for DPPH and ABTS radical scavenging activities. Results: All synthetic compounds possess good radical DPPH and ABTS scavenging potential in the ranges of IC50 = 2.11 ± 0.17 - 5.3 ± 0.11 μM and IC50 = 2.31 ± 0.06 - 5.5 ± 0.07 μM, respectively, as compared to standard ascorbic acid having IC50 = 2.02 ± 0.11 μM for DPPH and IC50 = 2.1 ± 0.07 μM for ABTS. Conclusion: These compounds could serve as leads for antioxidant activity that have the ability to control free radical generation and ward off free radical-induced disorders.


2021 ◽  
Vol 11 (3) ◽  
pp. 1008
Author(s):  
Kao-Wei Hung ◽  
Chao-Chien Chang ◽  
Thanasekaran Jayakumar ◽  
Marappan Velusamy ◽  
Chih-Wei Hsia ◽  
...  

Reactive oxygen species (ROS) play major role in inducing inflammation and related diseases. Our previous studies have revealed that the ruthenium (II)-compound, [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), inhibits hydroxyl radical (OH•) formation in human platelets. TQ-6 also have protective effect against induced inflammation in macrophages and hepatic injury in mice through NF-κB signaling. However, the free radical formation inhibitory mechanism of TQ-6 in macrophages is unclear. Therefore, this study detected the antioxidative ability of TQ-6 in both a cell-free system and in LPS-induced macrophages through electron spin resonance (ESR) spectrometry. TQ-6 reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH), galvinoxyl, and superoxide radicals in a cell-free system and OH• formation in macrophages. Additionally, TQ-6 activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and upregulated the antioxidant protein heme oxygenase-1 (HO-1) to elevate anti-inflammatory activity in LPS-induced macrophage cells and inhibited carrageenan-induced paw edema in a rat model. Therefore, TQ-6 may prevent oxidative stress and also act as an effective therapeutic agent for the treatment of oxidant-related diseases.


1991 ◽  
Vol 44 (8) ◽  
pp. 903-907 ◽  
Author(s):  
SHINICHIRO KATO ◽  
KAZUTOSHI SHINDO ◽  
YOKO KATAOKA ◽  
YUJI YAMAGISHI ◽  
JUNICHIRO MOCHIZUKI

1994 ◽  
Vol 182 (2) ◽  
pp. 159-162 ◽  
Author(s):  
C.L. Willis ◽  
B.S. Meldrum ◽  
P.B. Nunn ◽  
B.H. Anderton ◽  
P.N. Leigh

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1189
Author(s):  
Jangsoon Kim ◽  
See-Hyoung Park ◽  
Seyoung Yang ◽  
Sae Woong Oh ◽  
Kitae Kwon ◽  
...  

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon formed during the incomplete combustion of organic matter, has harmful effects. Therefore, much research is ongoing to develop agents that can mitigate the effects of B[a]P. The aim of this study was to examine the effect of maclurin, one component of the branches of Morus alba L., on the B[a]P-induced effects in HaCaT cells, a human keratinocyte cell line. Maclurin treatment inhibited aryl hydrocarbon receptor (AHR) signaling as evidenced by reduced xenobiotic response element (XRE) reporter activity, decreased expression of cytochrome P450 1A1 (CYP1A1), and reduced nuclear translocation of AHR. The B[a]P-induced dissociation of AHR from AHR-interacting protein (AIP) was suppressed by maclurin. Maclurin also inhibited the production of intracellular reactive oxygen species (ROS) induced by B[a]P. In addition, the antioxidant property of maclurin itself was demonstrated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Furthermore, maclurin activated antioxidant response element (ARE) signaling through enhancement of ARE luciferase reporter activity and the expression of ARE-dependent genes including nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1). Nrf2 activation and its nuclear translocation were promoted by maclurin through p38 MAPK activation. These data indicate that maclurin had antagonistic activity against B[a]P effects through activation of Nrf2-mediated signaling and inhibition of AHR signaling and, suggesting its potential in protecting from harmful B[a]P-containing pollutants.


INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (07) ◽  
pp. 14-22
Author(s):  
T. A Khan ◽  
◽  
A. Gohel

Biomolecules can be oxidized by free radicals. This oxidative damage has an important etiological role in aging and the development of diseases like cancer, atherosclerosis, and other inflammatory disorders. Synthetic antioxidants, such as butylated hydroxyl anisole, are good free radical scavengers; however, they can be carcinogenic. Therefore, there is an increasing interest in searching for antioxidants of natural origin. Acacia nilotica has a versatile medicinal value as folk medicine. The present study aims at screening the methanol and aqueous extracts of the pods of Acacia nilotica for antioxidant activity. The effect of these extracts on inhibition of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide radicals and of lipid peroxidation was studied. The results indicated that both the extracts exhibited a significant reduction in the DPPH and NO radical production along with a significant reduction in lipid peroxidation. The results indicate the pods of Acacia nilotica to be a cheap and easily available source of antioxidants


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