• The Journal of Korean Medicine
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• v.25 no.2
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• pp.173-183
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• 2004

Objectives : Oxidative stress can induce negative responses such as growth inhibition or cell death by necrosis or apoptosis due to the intensity of the oxidative stress, as well as positive responses such as cellular proliferation or activation. We examined the effect of Jihwangeumja on this process. Methods and Results : We analyzed the influence of oxidative stress and agents that modify its effect in human umbilical vein endothelial cell (HUVEC). Oxidative stress was induced by $B_2O_2$. With induced oxidative stress the results obtained indicate that it has a harmful effect over cell function and viability, and that this effect is dose and time dependent. When oxidative stress increased, Jihwangeumja reduced cell damage and had protective functions. $B_2O_2$, induced the apoptosis of HUVEC through the activation of intrinsic caspases pathway as well as mitochondrial dysfunction. A significant increase in cell survival was observed in culture cells with oxidative stress when they were treated with Jihwangeumja. Conclusions : These results suggest that Jihwangeumja may be potentially useful to treat HUVEC against oxidative damages mediated by modulation of caspase protease and mitochondrial dysfunction.

• Tuberculosis and Respiratory Diseases
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• v.68 no.2
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• pp.55-61
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• 2010

Background: The underlying pathogenesis of fat embolism-induced acute lung injury (ALI) has not been elucidated. In the present study, the pathogenesis of fat embolism-induced ALI was probed in association with neutrophilic oxidative stress in oleic acid (OA)-induced ALI of S-D rats. Methods: OA was injected intravenously to provoke ALI in experimental rats. Five hours later, indices of ALI were measured to confirm the role of the neutrophilic respiratory burst. The effect of an inhibition of phospholipase A2 (PLA2) was also evaluated. Results: The accumulation of neutrophils in the lung due to OA caused increased neutrophilic oxidative stress in lung, which was ameliorated by mepacrine. What were the results from inhibition of PLA2. Conclusion: Excess neutrophilic oxidative stress contributes to OA-induced ALI, which is lessened by the inhibition of PLA2.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.567-575
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• 2018

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.57-62
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• 2013

Objectives : Lonicerae Japonicae Flos (LJF) has been shown anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits skin injury against oxidative stress in human keratinocyte, HaCaT cells. The purpose of this study was to evaluate the protective effects of LJF against hydrogen peroxide($H_2O_2$)-induced oxidative stress in human keratinocytes, HaCaT cells. Methods : To evaluate out the protective effects of LJF on oxidative injury in HaCaT cells, an oxidative stress model of HaCaT cells was established under a suitable concentration (500 ${\mu}M$) hydrogen peroxide. HaCaT keratinocyte cells were pre-treated with LJF (0.1, 0.25 or 0.5 mg/ml), and then stimulated with $H_2O_2$. Then, the cells were harvested to measure the cell viability, DNA damage, and release of reactive oxygen species (ROS). Results : LJF (0.1, 0.25 or 0.5 mg/ml) itself did not show any significant toxicity in HaCaT cells. The treatment of $H_2O_2$ caused the oxidative stress, leading to the cell death, and DNA injury. However, pretreatment with LJF reduced cell death, and DNA injury. The stimulation of $H_2O_2$ on HaCaT cells resulted in excessive release of ROS, which is the main factor of oxidative stress. The excessive release of ROS was inhibited by LJF treatment significantly. Conclusions : These results could suggest that LJF exhibited the protective effects of HaCaT cells against $H_2O_2$-induced oxidative stress by inhibiting ROS release. It could be explained that LJF inhibit skin damages against oxidative stress. Thus, LJF would be useful for the development of drug or cosmetics treating skin troubles.

• Herbal Formula Science
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• v.25 no.2
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• pp.155-166
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• 2017

Objectives : Polygoni Multiflori Ramulus has been widely used as a traditional medicinal herb for the treatment of insomnia, limb pain and itch. The extract of Polygoni Multiflori Ramulus (PMRE) is known to have a modulatory effect of many inflammatory responses. This study was performed to investigate the hepatoprotective effect of PMRE against arachidonic acid (AA) + iron-induced oxidative stress on HepG2 cell and carbon tetrachloride ($CCl_4$)-induced liver injury on mice. Methods : The effects of PMRE on cell viability was assessed by MTT assay. And flow cytometric analysis was performed to estimate the effects on mitochondrial function. To investigate its underlying mechanism, apoptosis-related proteins were analysed by using immunoblot analysis. In addition, ICR mouse were administrated (po) with the PMRE (30, 100 mg/kg) for 3 days and then, injected (ip) with $CCl_4$ (0.5 ml/kg body weight) to induce acute liver damage. The level of pro-caspase-3 was measured. Results : Treatment of PMRE increased relative cell viability, prevented a cleavage of poly (ADP ribose) polymerase and pro-caspase-3, and also reduced mitochondrial membrane permeability against AA + iron-induced oxidative stress. In addition, PMRE treatment decreased liver injury induced by $CCl_4$, as evidenced by increases in pro-caspase-3 level. Conclusions : These results demonstrate that PMRE has an ability to anti-oxidant and hepatoprotective effect against AA + iron-induced oxidative stress and $CCl_4$-induced liver injury.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5071-5074
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• 2016

Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague-Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a rat model of colon cancer.

• Herbal Formula Science
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• v.11 no.2
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• pp.135-146
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• 2003

Objectives : Wolguk-whan has been used as a prescription of natural drug for the treatment of stress digestive system disease. Recently, we reported that Wolguk-whan methnol extract (WGWM) exerted a significant protective effect against oxidative damage to the liver of ICR mice. This study was purposed to investigate the effects of Wolguk-whan water extract (WGWW) on liver injury induced by oxidative stress. Methods : In order to investigate the effects of WGWW on acute liver injury, ICR mice were pretreated with WGWW for 6days, starved for 24hrs, and administerated acetamirtophen(500mg/kg, i.p.). In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results : In vivo administeration of WGWW showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that WGWW might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.479-491
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• 1998

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.139-145
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• 2009

The purpose of this study was to evaluate the effects of the water extract of Samultang (SMT), a Chinese herb, on apoptotic cell death by $H_2O_2$-induced oxidative stress in SK-N-M C cells. A nuclear fragmentation was observed via fluorescence imaging 12 h after exposure to 30 ${\mu}M$ $H_2O_2$ and DNA laddering was detected via agarose electrophoresis gel. In addition, increases in sub-G1 phase and cleavage of the PARP protein were observed. However, treatment with SMT for 2 h prior to $H_2O_2$ exposure significantly reduced apoptotic cell death induced by incubation with 30 ${\mu}M$ $H_2O_2$ in SK-N-MC cells. Pre-incubation with water extract of SMT for 2 h prevented the $H_2O_2$-induced decrease in mitochondrial transmembrane potential. SMT also attenuated the increase in caspase-3 activity and the breakdown of PARP protein caused by $H_2O_2$-induced oxidative stress. These results suggest that the water extract of SMT provides inhibition of apoptotic cell death against oxidative injury in SK-N-MC cells.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.159-168
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• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.