scholarly journals Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Ravirajsinh N. Jadeja ◽  
Kapil K. Upadhyay ◽  
Ranjitsinh V. Devkar ◽  
Sandeep Khurana

Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury. Several studies indicate that activation of Nrf2 signaling pathway ameliorates liver injury. The hepatoprotective potential of naturally occurring compounds has been investigated in various models of liver injuries. In this review, we comprehensively appraise various phytochemicals that have been assessed for their potential to halt acute and chronic liver injury by enhancing the activation of Nrf2 and have the potential for use in humans.

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhuqian Wang ◽  
Yange Liu ◽  
Xuyu Zhao ◽  
Shuyan Liu ◽  
Yang Liu ◽  
...  

Aronia melanocarpa (AM), which is rich in anthocyanins and procyanidins, has been reported to exert antioxidative and anti-inflammatory effects. This study aimed to systematically analyze the components of AM and explore its effects on alcohol-induced chronic liver injury in mice. A component analysis of AM revealed 17 types of fatty acids, 17 types of amino acids, 8 types of minerals, and 3 types of nucleotides. Chronic alcohol-induced liver injury was established in mice via gradient alcohol feeding over a period of 6 months, with test groups orally receiving AM in the last 6 weeks. AM administration yielded potential hepatoprotective effects by alleviating weight gain and changes in organ indexes, decreasing the ratio of alanine aminotransferase/aspartate aminotransferase, reducing lipid peroxidation, enhancing antioxidant activities, decreasing oxidation-related factor levels, and regulating inflammatory cytokine levels. Histological analyses suggest that AM treatment markedly prevented organ damage in alcohol-exposed mice. Furthermore, AM activated nuclear factor erythroid 2-like 2 (Nrf2) by downregulating the expression of Kelch-like ECH-associated protein 1, resulting in elevated downstream antioxidative enzyme levels. AM activated Nrf2 via modulation of the phosphatidylinositol-3-hydroxykinase/protein kinase B signaling pathway. Altogether, AM prevented alcohol-induced liver injury, potentially by suppressing oxidative stress via the Nrf2 signaling pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yasuhiro Nakagami

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases. The well-known Nrf2 activators, bardoxolone methyl and its derivatives, have been the subject of a number of clinical trials, including those aimed at treating chronic kidney disease, pulmonary arterial hypertension, and mitochondrial myopathies. Recent studies suggest that Nrf2 activation protects the retina from retinal diseases. In particular, this is supported by the finding that Nrf2 knockout mice display age-related retinal degeneration. Moreover, the concept has been validated by the efficacy of Nrf2 activators in a number of retinal pathological models. We have also recently succeeded in generating a novel Nrf2 activator, RS9, using a biotransformation technique. This review discusses current links between retinal diseases and Nrf2 and the possibility of treating retinal diseases by activating the Nrf2 signaling pathway.


2020 ◽  
Vol 73 ◽  
pp. S527
Author(s):  
Adil Bhat ◽  
Sudrishti Chaudhary ◽  
Gaurav Yadav ◽  
Anupama Parasar ◽  
Chhagan Bihari ◽  
...  

2020 ◽  
Vol 393 (6) ◽  
pp. 1067-1075 ◽  
Author(s):  
Ezhilarasan Devaraj ◽  
Anitha Roy ◽  
Geetha Royapuram Veeraragavan ◽  
Anitha Magesh ◽  
Aneymol Varikalam Sleeba ◽  
...  

2020 ◽  
Author(s):  
Golbarg Rahimi ◽  
Salime Heydari ◽  
Bahare Rahimi ◽  
Navid Abedpoor ◽  
Iman Nicktab ◽  
...  

Abstract Background: SPTC is a mix of four herbal components (Salvia officinalis, Panax ginseng, Trigonella foenum-graeceum, and Cinnamomum zeylanicum) which may prevent the development of AGEs rich diet-induced diabetic complication and liver injury via activating the nuclear factor erythroid-2-related-factor-2 (Nrf2) pathway. Nrf2, as a master regulator of antioxidant response elements by activating cytoprotective genes expression, decreases oxidative stress associated with hyperglycemia and increases insulin sensitivity. We hypothesized that the combined effect of SPTC along with exercise could efficiently moderate oxidative stress with more favorable effects in the treatment of diabetes.Methods: We induced diabetes in C57BL/6 mice by AGEs using a diet supplementation and limitation of physical activity. After 16 weeks of intervention, AGEs fed mice were compared to control mice. Diabetic mice were assigned into seven experimental groups (n=5): diabetic mice, diabetic mice treated with SPTC (130 mg/kg), diabetic mice treated with Salvia Officinalis (60 mg/kg), diabetic mice treated with metformin (300 mg/kg), diabetic mice with endurance exercise training, diabetic mice treated with SPTC+metformin (the same as mentioned), diabetic mice treated with SPTC+exercise trainingResults: SPTC+exercise and SPTC+metformin reduced diabetic complications like gain weight, water, and calorie intake, blood glucose, insulin, and GLUT4 content more efficiently than each treatmen. These combinations improved oxidative stress hemostasis by activating the Nrf2 signaling pathway and attenuating keap1 protein more significantly.Conclusions: Eventually, combined treatment of SPTC with exercise and metformin as a novel approach had more beneficial effects to prevent the development of diabetes and oxidative stress associated with hyperglycemia.


2008 ◽  
Vol 294 (2) ◽  
pp. R311-R320 ◽  
Author(s):  
Kohji Otogawa ◽  
Tomohiro Ogawa ◽  
Ryoko Shiga ◽  
Kazuki Nakatani ◽  
Kazuo Ikeda ◽  
...  

Oxidative stress due to iron deposition in hepatocytes or Kupffer cells contributes to the initiation and perpetuation of liver injury. The aim of this study was to clarify the association between dietary iron and liver injuries in rats. Liver injury was initiated by the administration of thioacetamide or ligation of the common bile duct in rats fed a control diet (CD) or iron-deficient diet (ID). In the acute liver injury model induced by thioacetamide, serum levels of aspartate aminotransferase and alanine aminotransferase, as well as hepatic levels of lipid peroxide and 4-hydroxynonenal, were significantly decreased in the ID group. The expression of 8-hydroxydeoxyguanosine and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling positivity showed a similar tendency. The expression of interleukin-1β and monocyte chemotactic protein-1 mRNA was suppressed in the ID group. In liver fibrosis induced by an 8-wk thioacetamide administration, ID suppressed collagen deposition and smooth muscle α-actin expression. The expressions of collagen 1A2, transforming growth factor β, and platelet-derived growth factor receptor β mRNA were all significantly decreased in the ID group. Liver fibrosis was additionally suppressed in the bile-duct ligation model by ID. In culture experiments, deferoxamine attenuated the activation process of rat hepatic stellate cells, a dominant producer of collagen in the liver. In conclusion, reduced dietary iron is considered to be beneficial in improving acute and chronic liver injuries by reducing oxidative stress. The results obtained in this study support the clinical usefulness of an iron-reduced diet for the improvement of liver disorders induced by chronic hepatitis C and alcoholic/nonalcoholic steatohepatitis.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Guo-Hui Li ◽  
Yan-Ru Li ◽  
Ping Jiao ◽  
Yu Zhao ◽  
Hui-Xin Hu ◽  
...  

Oxidative stress plays a central role in the pathogenesis of many human diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the intracellular antioxidant response and is an emerging target for the prevention and therapy of oxidative stress-related diseases. Salviae Miltiorrhizae Radix et Rhizoma (SMRR) is a traditional Chinese medicine (TCM) and is commonly used for the therapy of cardiac cerebral diseases. Cumulative evidences indicated that the extract of SMRR and its constituents, represented by lipophilic diterpenoid quinones and hydrophilic phenolic acids, were capable of activating Nrf2 and inhibiting oxidative stress. These bioactive constituents demonstrated a therapeutic potential against human diseases, exemplified by cardiovascular diseases, neurodegenerative diseases, diabetes, nephropathy, and inflammation, based on the induction of Nrf2-mediated antioxidant response and the inhibition of oxidative stress. In the present review, we introduced the SMRR and Nrf2 signaling pathway, summarized the constituents with an Nrf2-inducing effect isolated from SMRR, and discussed the molecular mechanism and pharmacological functions of the SMRR extract and its constituents.


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