• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.363-370
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• 2021

This study was conducted to evaluate the dermal cytotoxicity of lead acetate (LA) and other heavy metal compounds, and the protective effect of Lespedeza bicolor (LB) extract on LA-induced cytotoxicity in cultured B16-/F10 melanoma cells. The study evaluated the antioxidative effects of LB due to its electron-donating ability (EDA), inhibitory effects on melanization and improving cell viability. LA significantly decreased cell viability in a dose-dependent manner, and the XTT₅₀ value was determined at 52.7 µM in the studied cultures. Based on the Borenfreund and Puerner's toxicity criteria, LA was estimated to be highly cytotoxic. LA-induced cytotoxicity and cell damage was reversed by the antioxidant activity of kaempferol (KAE), thereby remarkably improving cell viability. A study of the protective effects of the LB extract on LA-induced cytotoxicity showed that the LB extract remarkably increased cell viability in the LA-treated group, and also inhibited the EDA and the total amount of melanin. The above results suggest oxidative stress-mediated cytotoxicity of LA. In the study, LB extract effectively prevented LA-induced cytotoxicity via its antioxidative activity and inhibition of melanization. In conclusion, natural resources like LB extracts may be useful agents for the prevention of oxidative stress-mediated cytotoxicity and melanization by heavy metallic compounds such as LA.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.685-696
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• 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 Life Science
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• v.31 no.3
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• pp.338-345
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• 2021

Zizania latifolia has long been used as a tea for both edible and medicinal purposes. However, research into the use of Z. latifolia as a high value-added edible material is lacking. In a previous study, we confirmed that tricin is the major component in Z. latifolia. In this study, we investigated the protective effect of a Z. latifolia extract (ZLE). Toxicity tests of ZLE or tricin on HepG2 cells revealed no toxicity due to ZLE or tricin at all concentrations used. The reduction in cell viability by tert-butyl hydroperoxide (t-BHP) was suppressed by treatment with ZLE or tricin. In addition, ZLE or tricin effectively inhibited the production of reactive oxygen species (generation of hydrogen peroxide, alkoxy free radicals, and peroxyl free radicals by t-BHP) and oxidative damage. ZLE or tricin treatments also increased the protein expression of superoxide dismutase 1 (SOD1), catalase, heme oxygenase-1 (HO-1), and nuclear factor erythroid-related factor 2 (Nrf2), which are known as antioxidant enzymes, suggesting that the protective effect of ZLE is related to activation of tricin. Taken together, the results indicate that Z. latifolia can be developed as a functional food material for improving liver function.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.3
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• pp.213-223
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• 2022

In this study, the anti-inflammatory and antioxidant effects of aerial parts of Rumex acetosa L. extract were confirmed to prevent various inflammatory diseases and skin aging caused by excessive oxidative stress. As a result of ABTS assay, it was confirmed that the radical scavenging ability increased in a concentration-dependent manner. ROS inhibitory ability was confirmed through DCF-DA assay, and concentration-dependent inhibition of ROS production was confirmed. The effect of inhibiting cell nuclear damage according to ROS was confirmed through DAPI staining. In addition, it was confirmed that the mRNA expression levels of iNOS and COX-2 were inhibited in a concentration-dependent manner through qPCR. As a result of confirming the protein levels of iNOS and COX-2 by western blotting, iNOS was significantly decreased at all concentrations, and COX-2 was significantly decreased at 800 ㎍/mL. The inhibitory effect on the production of NO generated by iNOS was confirmed by NO assay, and NO was decreased in a concentration-dependent manner. In addition, phosphorylation of ERK and JNK in the MAPKs signaling pathway were inhibited. Therefore, Rumex acetosa L. has the potential to be used as an anti-inflammatory and antioxidant cosmetic raw material by showing anti-inflammatory and antioxidant effects through the MAPKs pathway.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

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

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.659-667
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• 2017

The present study was designed to evaluate the antioxidant activity and radioprotective effects of Naringin and Naringenin in ${\gamma}$-irradiated mice. The antioxidant activity of Naringin and Naringenin was evaluated by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Healthy female BALB/c mice were administered Naringin and Naringenin orally ($90{\mu}M/dose$ and $180{\mu}M/dose$) for 7 consecutive days prior to ${\gamma}$-irradiation (6 Gy). Naringenin displayed a much higher antioxidant activity in ABTS and FRAP than naringin. ${\gamma}$-irradiation resulted in cellular damage with decreased spleen and thymus indices and white blood cells (WBC) count. Additionally, ${\gamma}$-irradiation significantly increased lipid peroxidation and decreased the levels of antioxidant enzymes and glutathione (GSH) in the liver tissue. Strikingly, prior administration of Naringenin resulted in considerable prevention of these symptoms. Protection against ${\gamma}$-irradiation-induced cellular damage by Naringenin is likely due to its higher its antioxidant activity. Together, these results confirm that Naringenin is a potent antioxidant and radioprotector.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.1
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• pp.87-94
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• 2016

Skin damage is mainly caused by environmental factors such as ultraviolet light, heat, and smoking. It is known that reactive oxygen species production is commonly involved in the pathogenesis of skin damage induced by these factors, causing skin aging. Pyrus pyrifolia Nakai continues to be a popular and highly consumed fruit in many countries with known beneficial effects including antitumor, antioxidative, and anti-inflammatory effects. However, there is no evidence of a therapeutic effect of Pyrus pyrifolia extract (PPE) against skin aging via inhibition of mitochondria-mediated apoptosis. In this study, we investigated PPE protective effect against photoaging induced by UVB ($50mJ/cm^2$) in HS68 human dermal fibroblasts. Lactate dehydrogenase assay showed that PPE significantly protected HS68 cells against UVB-induced damage in a dose-dependent manner. Other assays using DCF-DA demonstrated that PPE protected HS68 cells by regulating reactive oxygen species production. PPE also regulated mitochondrial dysfunction and mitochondrial membrane potential induced by UVB, and inhibited UVB-induced caspase-3 activity. These results indicate that PPE protects human dermal fibroblasts from UVB-induced damage by regulating the oxidative defense system.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.41-51
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• 2015

Objectives : This study was performed to investigate the effects of $LR_3$ and $SP_6$ acupuncture on renal damage in streptozotocin(STZ)-induced diabetic mice. Methods : ICR male mice were stabilized for a week and divided into four groups: a normal mice group(N), no-acupuncture diabetic mice group(Control), $LR_3$ acupuncture diabetic mice group($LR_3$), and $SP_6$ acupuncture diabetic mice group($SP_6$). Diabetes was experimentally induced by intraperitoneal injection of STZ(150 mg/kg) in citrate buffer(pH 4.5). For two weeks, $LR_3$ and $SP_6$ acupunctures were administered bilaterally at each point once a day. After two weeks, the animals' weight was measured and they underwent a laparotomy. Serum glucose and blood urea nitrogen(BUN) were measured from the blood taken from the heart. We measured glucose, reactive oxygen species(ROS), peroxynitrite($ONOO^-$) and thiobarbituric acid reactive substances(TBARS) in the kidney and compared expression levels of superoxide dismutases(SOD), glutathione peroxidase(GPx), nuclear factor-kappa B(NF-${\kappa}B$), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase(iNOS) and Interleukin-1 beta(IL-$1{\beta}$). Results : BUN significantly decreased in $LR_3$, $SP_6$ compared to the control group. $LR_3$ showed significantly decreased glucose compared to the control group. $LR_3$, $SP_6$ significantly decreased in ROS and $ONOO^-$ compared to the control group. $LR_3$ significantly decreased in TBARS compared to the control group. $SP_6$ significantly increased in expressions of SOD-1, catalase, and GPx compared to the control group. $LR_3$, $SP_6$ significantly decreased in COX-2 compared to the control group. $SP_6$ significantly decreased in IL-$1{\beta}$ compared to the control group. Conclusions : This study suggests that $LR_3$ acupuncture may be effective in controlling glucose and lipid peroxidation and that $SP_6$ acupuncture may have anti-oxidative and anti-inflammatory effects on renal damage in STZ-induced diabetic mice.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.