• Biomolecules & Therapeutics
• /
• v.30 no.6
• /
• pp.490-500
• /
• 2022

Aging is defined as physiological dysfunction of the body and a key risk factor for human diseases. During the aging process, cellular senescence occurs in response to various extrinsic and intrinsic factors such as radiation-induced DNA damage, the activation of oncogenes, and oxidative stress. These senescent cells accumulate in many tissues and exhibit diverse phenotypes, such as resistance to apoptosis, production of senescence-associated secretory phenotype, cellular flattening, and cellular hypertrophy. They also induce abnormal dysfunction of the microenvironment and damage neighboring cells, eventually causing harmful effects in the development of various chronic diseases such as diabetes, cancer, and neurodegenerative diseases. Thus, pharmacological interventions targeting senescent cells, called senotherapeutics, have been extensively studied. These senotherapeutics provide a novel strategy for extending the health span and improving age-related diseases. In this review, we discuss the current progress in understanding the molecular mechanisms of senotherapeutics and provide insights for developing senotherapeutics.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.3
• /
• pp.596-605
• /
• 2024

Anthocyanins belong to phenolic pigments and are known to have various pharmacological activities. This study aimed to investigate whether anthocyanins could inhibit hydrogen peroxide (H₂O₂)-induced oxidative damage in human retinal pigment epithelial ARPE-19 cells. Our results indicated that anthocyanins suppressed H₂O₂-induced genotoxicity, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione. Anthocyanins also suppressed H₂O₂-induced apoptosis by reversing the Bcl-2/Bax ratio and inhibiting caspase-3 activation. Additionally, anthocyanins attenuated the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Moreover, anthocyanins increased the expression of heme oxygenase-1 (HO-1) as well as its activity, which was correlated with the phosphorylation and nuclear translocation of nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the cytoprotective and anti-apoptotic effects of anthocyanins were significantly attenuated by the HO-1 inhibitor, demonstrating that anthocyanins promoted Nrf2-induced HO-1 activity to prevent ARPE-19 cells from oxidative stress. Therefore, our findings suggest that anthocyanins, as Nrf2 activators, have potent ROS scavenging activity and may have the potential to protect ocular injury caused by oxidative stress.

• Animal Bioscience
• /
• v.36 no.7
• /
• pp.1120-1129
• /
• 2023

Objective: This study aimed to determine the protective efficacy of Buddha's Temple (BT) extract against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in Gallus gallus chicken embryo fibroblast cell line (DF-1) and its effects on the cell lipid metabolism. Methods: In this experimental study, Gallus gallus DF-1 fibroblast cells were pretreated with BT 10^-7 for 24 hours, followed by their six-hour exposure to t-BHP (100 μM). Water-soluble tetrazolium salt-8 (WST-8) assays were performed, and the growth curve was computed. The intracellular gene expression changes caused by BT extract were confirmed through quantitative polymerase chain reaction (qPCR). Flow cytometry, oil red O staining experiment, and thin-layer chromatography were performed for the detection of intracellular metabolic mechanism changes. Results: The WST-8 assay results showed that the BT pretreatment of Gallus gallus DF-1 fibroblast cell increased their cell survival rate by 1.08%±0.04%, decreased the reactive oxygen species (ROS) level by 0.93%±0.12% even after exposure to oxidants, and stabilized mitochondrial activity by 1.37%±0.36%. In addition, qPCR results confirmed that the gene expression levels of tumor necrosis factor α (TNFα), TIR domain-containing adapter inducing IFN-beta (TICAM1), and glucose-regulated protein 78 (GRP78) were regulated, which contributed to cell stabilization. Thin-layer chromatography and oil red O analyses showed a clear decrease in the contents of lipid metabolites such as triacylglycerol and free fatty acids. Conclusion: In this study, we confirmed that the examined BT extract exerted selective protective effects on Gallus gallus DF-1 fibroblast cells against cell damage caused by t-BHP, which is a strong oxidative inducer. Furthermore, we established that this extract significantly reduced the intracellular ROS accumulation due to oxidative stress, which contributes to an increase in poultry production and higher incomes.

• Nutrition Research and Practice
• /
• v.14 no.3
• /
• pp.203-217
• /
• 2020

BACKGROUND/OBJECTIVE: Centella asiatica, also known as Gotu kola, is a tropical medicinal plant native to Madagascar, Southeast Asia, and South Africa. It is well known to have biological activities, including wound healing, anti-inflammatory, antidiabetic, cytotoxic, and antioxidant effects. The purpose of this study was to determine the efficacy of extracts of C. asiatica against age-related eye degeneration and to examine their physiological activities. MATERIALS/METHODS: To determine the effects of CA-HE50 (C. asiatica 50% EtOH extract) on retinal pigment cells, we assessed the cytotoxicity of CoCl₂ and oxidized-A2E in ARPE-19 cells and observed the protective effects of CA-HE50 against N-methyl-N-nitrosourea (MNU)-induced retinal damage in C57BL/6 mice. In particular, we measured factors related to apoptosis and anti-oxidation and the protein levels of rhodopsin/opsin. We also measured glucose uptake to characterize glucose metabolism, a major factor in cell protection. RESULTS: Induction of cytotoxicity with CoCl₂ and oxidized-A2E inhibited decreases in the viability of ARPE-19 cells when CA-HE50 was administered, and promoted glucose uptake under normal conditions (P < 0.05). In addition, CA-HE50 inhibited degeneration/apoptosis of the retina in the context of MNU-induced toxicity (P < 0.05). In particular, CA-HE50 at 200 mg/kg inhibited the cleavage of pro-caspase-3 and pro-poly (ADP-ribose)-polymerase and maintained the expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 similar to normal control levels. Rhodopsin/opsin expression was maintained at a higher level than in normal controls. CONCLUSION: A series of experiments confirmed that CA-HE50 was effective for inhibiting or preventing age-related eye damage/degeneration. Based on these results, we believe it is worthwhile to develop drugs or functional foods related to age-related eye degeneration using CA-HE50.

• Journal of Life Science
• /
• v.33 no.10
• /
• pp.776-782
• /
• 2023

Silymarin, which is derived from dried Silybum marianum (milk thistle) seeds and fruits, possesses various beneficial properties, such as hepatoprotective, antioxidative, anti-inflammatory, and anticancer activity. This research aimed to explore the antioxidative activity of silymarin against oxidative stress and understand its molecular mechanism in RAW 264.7 cells. The study employed cell viability and reactive oxygen species (ROS) formation assays and western blot analysis. The results demonstrated that silymarin effectively reduced intracellular ROS levels induced by lipopolysaccharide (LPS) in a dose-dependent manner without causing any cytotoxic effects. Moreover, silymarin treatment significantly upregulated the expression of heme oxygenase (HO)-1, a phase II enzyme known for its potent antioxidative activity. Additionally, silymarin treatment significantly induced the expression of nuclear factor-erythroid 2 p45-related factor (Nrf) 2, a transcription factor responsible for regulating antioxidative enzymes, which was consistent with the upregulated HO-1 expression. To investigate the involvement of key signaling pathways in maintaining cellular redox homeostasis against oxidative stress, the phosphorylation status of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) was estimated by western blot analysis. The results showed that silymarin potently induced HO-1 expression, which was mediated by the phosphorylation of p38 MAPK. To further validate the antioxidative potential of silymarin-induced HO-1 expression, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was employed and attenuated by silymarin treatment, as identified by a selective inhibitor for each signaling molecule. In conclusion, silymarin robustly enhanced antioxidative activity by inducing HO-1 via the Nrf2/p38 MAPK signaling pathway in RAW 264.7 cells.

• Molecules and Cells
• /
• v.38 no.8
• /
• pp.734-740
• /
• 2015

Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson' disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo. We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells. When injected into mice on a subchronic schedule, amitriptyline induced movement deficits in the pole test, which is known to detect nigrostriatal dysfunction. In addition, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was reduced in amitriptyline-injected mice. Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.

• Journal of Microbiology and Biotechnology
• /
• v.33 no.8
• /
• pp.992-997
• /
• 2023

Ferroptosis is a new kind of programmed cell death of which occurrence in microorganisms is not clearly verified. The elevated level of reactive oxygen species (ROS) influences cellular metabolisms through highly reactive hydroxyl radical formation under the iron-dependent Fenton reaction. Iron contributes to ROS production and acts as a cofactor for lipoxygenase to catalyze poly unsaturated fatty acid (PUFA) oxidation, exerting oxidative damage in cells. While ferroptosis is known to take place only in mammalian cells, recent studies discovered the possible ferroptosis-like death in few specific microorganisms. Capacity of integrating PUFA into intracellular membrane phospholipid has been considered as a key factor in bacterial or fungal ferroptosis-like death. Vibrio species in bacteria and Saccharomyces cerevisiae in fungi exhibited certain characteristics. Therefore, this review focus on introducing the occurrence of ferroptosis-like death in microorganisms and investigating the mode of action underlying the cells based on contribution of lipid peroxidation and iron-dependent reaction.

• Preventive Nutrition and Food Science
• /
• v.16 no.4
• /
• pp.313-320
• /
• 2011

The oxidative stress level and antioxidant activities in two green algae (Ulva pertusa and Ulva linza), two brown algae (Agarum cribrosum and Dictyota dichotoma), and three red algae (Grateloupia lanceolata, Carpopeltis affinis, and Gracilaria verrucosa) collected from intertidal regions of Korea were assessed. In the two green algae, although the total glutathione content was not as high as that of the brown algae, the glutathione pool was extremely reduced, and the glutathione reductase (GRd)/glutathione peroxidase (GPx) activity ratio was high, which apparently plays an important role for protection against oxidative damage, as manifested by low lipid peroxidation. In the brown algae, which exhibited a low lipid peroxidation level that was comparable to the green algal species, the highest glutathione content, together with high GPx activity, appears to be the most important factor in their antioxidant protection. The red algal species exhibited extremely high lipid peroxidation levels. They also contained the lowest and most oxidized glutathione among the species, as well as the lowest GRd activity. In spite of the marked difference in the glutathione content, the significant difference in the activity of ${\gamma}$-glutamylcysteine ligase, the rate limiting enzyme for glutathione synthesis, among the species was not exhibited. Our results suggest that there is a significant difference in the levels of oxidative stress and antioxidant capacity among the algal species, and that the glutathione system, especially the efficiency of glutathione recycling, plays a vital role in antioxidative protection in algal species.

• Biomolecules & Therapeutics
• /
• v.29 no.6
• /
• pp.685-696
• /
• 2021

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.

• Journal of Microbiology and Biotechnology
• /
• v.23 no.3
• /
• pp.405-413
• /
• 2013

Monocyte chemotactic protein-3 (MCP-3), a chemokine that is in a superfamily of structurally related small chemotactic cytokines involved in leukocyte trafficking, is regarded as a key factor in atherogenesis. In this study, we examined the changes in atherogenic parameters including hepatic lipid accumulation and oxidative balance in MCP- 3-overexpressing transgenic mice (MCP-3 mice) under atherogenic conditions. To induce an extreme atherogenic condition, mice were fed a high-fat, high-cholesterol (HFHC) diet for 12 weeks. The body weight and food intake were not changed by MCP-3 overexpression in the aorta. On a HFHC diet, the MCP-3 mice had higher plasma levels of total cholesterol and a higher atherogenic index compared with wild-type mice, although there were no differences in the plasma HDL-cholesterol and triglyceride levels. Furthermore, an increase in lipid accumulation was observed in the aortas as well as the livers of the HFHC diet-fed MCP-3 mice compared with wild-type mice. The activities of antioxidant enzymes increased in the livers of the HFHC diet-fed MCP-3 mice, whereas supplementation with antioxidants, naringin and hesperidin, reversed the activities of the hepatic antioxidant enzymes in HFHC diet-fed MCP-3 mice, indicating that there might be more oxidative damage to the tissues in the HFHC diet-fed MCP-3 mice leading to progression towards atherosclerosis and hepatic steatosis. Microarray analyses of the aorta revealed atherosclerosis-, PPARs-, lipoprotein receptor, and apolipoprotein-related genes that were affected by the HFHC diet in MCP-3 mice. These findings suggest that aortic MCP-3 overexpression may contribute to the development of atherosclerosis and hepatic steatosis under atherogenic conditions.