• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.40-45
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• 2005

Ursodeoxycholic acid (UDCA) has long been used as an adjuvant or first choice of therapy for liver disease. Commonly, UDCA has been reported to play a role in improving hyperbilirubinemia and disorder of bromsulphalein. More commonly, UDCA has been used in reducing the rate of cholesterol level in bile juice that can cause cholesterol stone. The effects on the promotion of bile acid release that leads an excretion of toxic materials and wastes produced in liver cells as well as various arrays of liver disease such as hepatitis. Other than already reported in clinical use, immunosuppressive effect has been studied, especially in transplantation. In the study, we hypothesized that UDCA might have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials in the brain macrophages, microglia. We found that the treatment of $200\;{\mu}g/ml$ UDCA effectively suppressed the pro-inflammatory mediators (i.e. nitric oxide and interleukin-$1{\beta}$) in rat microglia compared to comparators. Interestingly, RT-PCR analysis suggested that UDCA strongly attenuated the expression of $IL-1{\beta}$ that was comparable with cyclosporine A at 48 h incubation. Conclusively, we found that UDCA may playa cytoprotective role in microglial cells through direct or indirect pathways by scavenging a toxic compound or an anti-inflammatory effect, which are known as major causes of neurodegenerative diseases.

• Natural Product Sciences
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• 제15권4호
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• pp.185-191
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• 2009

Intestinal epithelial cells (IEC) play an important role in the mucosal immune system. IEC-derived mediators of inflammatory cascades play a principal role in the development of colon inflammation. The aim of this study was to investigate the inhibitory effect of aqueous extracts of Schizandra chinensis fruits (SC-Ex) on the production of inflammatory mediators by the human colonic epithelial cells. HT-29 cells were stimulated with dextran sulfate sodium in the presence or absence of SC-Ex to examine the cytoprotection and production of IL-8 and reactive oxygen species (ROS). It was shown that dextran sulfate sodium (DSS) caused the reduction of cell viability and production of IL-8 and ROS in DSS-treated HT-29 cells. We observed that the treatment of SC-Ex protected significantly cell proliferation from DSS-induced damage in dose-dependent manner. SC-Ex (10 and 100 ${\mu}g$/ml) also suppressed DSS-induced production of IL-8 mRNA and protein. Moreover, DSS-induced ROS production was inhibited markedly by the treatment of 100 ${\mu}g$/ml SC-Ex. These results suggest that SC-Ex has the protective effects on DSS-induced cell damage and the release of inflammatory mediators in the intestinal epithelial cells.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.225-241
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• 2018

Taurine is an abundant, ${\beta}-amino$ acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.

• Toxicological Research
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• 제23권3호
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• pp.207-214
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• 2007

Chronic oxidative stress produced by exposure to environmental chemicals or pathophysiological states can lead animals to aging, carcinogenesis and degenerative diseases. Indirect antioxidative mechanisms, in which natural or synthetic agents are used to coordinately induce the expression of cellular antioxidant capacity, have been shown to protect cells and organisms from oxidative damages. Electrophile and free radical detoxifying enzymes, which were originally identified as the products of genes induced by cancer chemopreventive agents, are members of this protective system. The NFE2 family transcription factor Nrf2 was found to govern expression of these detoxifying enzymes, and screening for Nrf2-regulated genes has identified many gene categories involved in maintaining cellular redox potential and protection from oxidative damage as Nrf2 downstream genes. Further, studies using Nrf2-deficient mice revealed that these mutant mice showed more susceptible phenotypes towards exposure to environmental chemicals/carcinogens and in oxidative stress related disease models. With the finding that cancer chemopreventive efficacy of indirect antioxidants (enzyme inducers) is lost in the absence of Nrf2, a central role of Nrf2 in the antioxidative protective system has been firmly established. Promising results from cancer prevention clinical trials using enzyme inducers propose that pharmacological interventions that modulate Nrf2 can be an effective strategy to protect tissues from oxidative damage.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.75-84
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• 2016

This study was designed to investigate the cytoprotective effect of rosmarinic acid (RA) on ultraviolet B (UVB)-induced oxidative stress in HaCaT keratinocytes. RA exerted a significant cytoprotective effect by scavenging intracellular ROS induced by UVB. RA also attenuated UVB-induced oxidative macromolecular damage, including protein carbonyl content, DNA strand breaks, and the level of 8-isoprostane. Furthermore, RA increased the expression and activity of superoxide dismutase, catalase, heme oxygenase-1, and their transcription factor Nrf2, which are decreased by UVB radiation. Collectively, these data indicate that RA can provide substantial cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and has potential to be developed as a medical agent for ROS-induced skin diseases.

• 한국약용작물학회지
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• 제17권1호
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• pp.8-14
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• 2009

Pueraria lobata (Willd.) Ohwi was investigated to check its modulatory effects on the activation of macrophages upon inflammatory conditions treatment. For this purpose, we examined several inflammatory responses such as nitric oxide (NO) production, reactive oxygen species (ROS) generation, cytoprotection and phagocytosis under the treatment of methanol extract from P. lobata (Pl-ME). Pl-ME dose-dependently blocked NO production in lipopolysaccharide (LPS)- stimulated RAW264.7 cells but not sodium prusside (SNP)-generated NO release. The NO inhibition seemed to be due to blocking inducible NO synthase (iNOS), since Pl-ME suppressed its expression in a NF-${\kappa}B$-independent manner. Similarly, this extract also effectively protected RAW264.7 cells from LPS-induced cytotoxicity. However, Pl-ME did not block ROS generation and rather it enhanced. Finally, this extract negatively modulated FITC-dextran uptake. Therefore, our data suggested that Pl-ME may be involved in negatively regulating some macrophage-mediated inflammatory responses such as NO production and phagocytic uptake.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1251-1256
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• 2005

In this study, we evaluated the cytoprotective effects of antioxidative substances in hydrogen peroxide ($H_{2}O_{2}$) treated Mel-Ab melanocytes. Tested substances include selenium, quercetin, green tea (GT) extract, and several vitamins (ascorbic acid, Trolox, and folic acid). Of these, both quercetin and GT extract were found to have strong cytoprotective effects on $H_{2}O_{2}$­induced cell death. We also examined additive effects, but no combination of two of any of the above substances was found to act synergistically against oxidative damage in Mel-Ab cells. Nevertheless, a multi-combination of GT extract, quercetin, and folic acid appeared to prevent cellular damage in a synergistic manner, which suggests that combinations of antioxidants may be of importance, and that co-treatment with antioxidants offers a possible means of treating vitiligo, which is known to be related to melanocyte oxidative stress.

• 한국약용작물학회지
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• 제23권2호
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• pp.144-149
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• 2015

The peel of Citrus sunki exhibits multiple biological activities such as anti-oxidant, anti-inflammation and anti-obesity, but little is known about neurodegeneration-related activities. In this study, we investigated the protective effect of ethanolic extract from both immature and mature Citrus sunki peel on neuronal cell death. Treatment of the neuroblastoma cell line SH-SY5Y with $MPP^+$, an inducer of Parkinson disease model, increased cell death in a dose dependent manner. Increased levels of active caspase-3 and cleaved PARP were detected. Treatment with immature Citrus sunki peel extract significantly reduced $MPP^+$-induced neurotoxicity. Cytoprotection with immature Citrus sunki peel extract was associated with a decrease in caspase-3 activation and PARP cleavage. In contrast, mature Citrus sunki peel extract had no significant effects. These data suggest that immature Citrus sunki peel extract may exert anti-apoptotic effect through the inhibition of caspase-3 signaling pathway on $MPP^+$-induced neuronal cell death.

• Animal Bioscience
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• 제34권6호
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• pp.1006-1013
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• 2021

Objective: Cells have increased susceptibility to activation of apoptosis when suffering heat stress (HS). An effective supplementation strategy to mimic heat-induced apoptosis of bovine mammary epithelial cells (MECs) is necessary to maintain optimal milk production. This study aimed to investigate possible protective effects of the anti-apoptotic activity of 5-aminolevulinic acid (5-ALA) against HS-induced damage of bovine MECs. Methods: Bovine MECs were pretreated with or without 5-ALA at concentrations of 10, 100, and 500 µM for 24 h followed by HS (42.5℃ for 24 h and 48 h). Cell viability was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress genes. Results: We found that 5-ALA induces cytoprotection via inhibition of apoptosis markers after HS-induced damage. Pretreatment of bovine MECs with 5-ALA resulted in dramatic upregulation of mRNA for nuclear factor erythroid-derived 2-like factor 2, heme oxygenase-1, and NAD(P)H quinone oxidoreductase 1, all of which are antioxidant stress genes. Moreover, 5-ALA pretreatment significantly suppressed HS-induced ER stress-associated markers, glucose-regulated protein 78, and C/EBP homologous protein expression levels. Conclusion: 5-ALA can ameliorate the ER stress in heat stressed bovine MEC via enhancing the expression of antioxidant gene.

• Molecules and Cells
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• 제46권3호
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• pp.142-152
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• 2023

Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.