Oxidative stress induced by reactive oxygen intermediates has been implicated in a variety of human diseases including neurodegenerative disorders, cancer, cardiovascular and respiratory diseases, and mode of action of environmental toxicants. Tert-butylhydroperoxide (t-BHP) is an organic lipid hydroperoxide analogue, which is commonly used as a pro-oxidant for evaluating mechanisms involving oxidative stress in cells and tissues. In this study, the underlying mechanisms involved in the protective effects of Hwabuk 94 kiwifruit (Actinidia deliciosa cv. 'Hwabuk 94'), which is cultivated in Jeju, on the t-BHP-induced cytotoxicity in PC12 cell. The pretreatment of rat pheochromocytoma cell line PC12 with Hwabuk 94 extract ($1-100\;{\mu}g/ml$) resulted in a significant recovery from t-BHP-induced cell death and increased Bcl-2 and procaspase-3 expression, whereas the expression of Bax and cleaved PARP were decreased in a dose-dependent manner compared to the control. Furthermore, Hwabuk 94 inhibited the t-BHP-induced p38 MAP kinase and extracellular signal-regulated kinase 1/2, but not c-Jun N-terminal kinase activations. Finally, these findings suggest that Hwabuk 94 kiwifruit might attenuate t-BHP-induced PC12 cell cytotoxicity, at least in part, through the inhibition of signaling pathways mediated by the ERK1/2 and p38 MAP kinase.
Kim, Jihyun;Kim, Jaehoon;Huang, Zhouchi;Goo, Nayeon;Bae, Ho Jung;Jeong, Yongwoo;Park, Ho Jae;Cai, Mudan;Cho, Kyungnam;Jung, Seo Yun;Bae, Soo Kyung;Ryu, Jong Hoon
Biomolecules & Therapeutics
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v.27
no.3
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pp.327-335
/
2019
As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.
L-carnitine is found in high levels in muscle tissues. It has been developed as a nutrient and dietary supplement, and also used as a therapeutic supplement in various diseases including type II diabetes, osteoporosis and metabolic neuropathies. However, it is not fully understood how it affects cellular mechanisms in colorectal cancer. Therefore, we attempted to determine the effect of L-carnitine in HCT116 human colorectal cancer cells. First, the HCT116 cells were exposed to L-carnitine for 24 hours at 0-40 mM, and then analyzed for cellular proliferation, oxidative stress and related mechanisms. In a MTT assay, L-carnitine inhibited cellular proliferation and induced reactive oxygen species (ROS) in HCT116 by DCF-DA analysis. To analyze the mechanism of L-carnitine in colorectal cancer cells, we performed a western blot analysis for pERK1/2 and pp38 MAP kinase. The western blot showed that L-carnitine significantly increased protein levels of pERK1/2 and pp38 compared with control. Taken together, we found that L-carnitine has anti-proliferative function via increased ROS and activation of ERK1/2 and p38 pathway in HCT116. These findings suggest that L-carnitine may have an anti-proliferative role on colorectal cancer.
Kim, Kyong;Kwak, Min-Kyu;Bae, Gong-Deuk;Park, Eun-Young;Baek, Dong-Jae;Kim, Chul-Young;Jang, Se-Eun;Jun, Hee-Sook;Oh, Yoon Sin
Nutrition Research and Practice
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v.15
no.3
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pp.294-308
/
2021
BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.
Lee, Jin A;Lee, Tae Jong;Kim, Jin Young;Shin, Mi-Rae;Park, Hae-Jin;Roh, Seong-Soo
The Korea Journal of Herbology
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v.37
no.5
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pp.63-74
/
2022
Objective : Gastritis refers to an inflammatory disease of the gastric mucosa. Alcohol is one of the main aggression factors, causing bleeding and inflammation in the gastric mucosa and it is known to not only increase lipid peroxide levels, but also deplete key antioxidant factors. The purpose of this study was to determine the effect of Uncariae Ramulus et Uncus water extract (URW) in alcohol-induced gastritis. Methods : The total polyphenol and flavonoid contents of URW were confirmed through an in vitro experiment. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity and ferric reducing antioxidant power (FRAP) activity were confirmed. For in vivo experiments, mice were divided into 4 groups (n=8). Also, 1 hr after oral administration of each drug, 50% ethanol was orally administered to induce gastritis. Results : As a result of in vitro experiments, URW showed excellent antioxidant activity. In alcohol-induced gastritis, URW alleviated the damage to the gastric mucosa caused by alcohol. Also, URW decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in serum and gastric tissues, and significantly decreased the expression of NADPH oxidases in gastric tissues. In addition, it significantly modulated the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and nuclear factor-𝜅B p65 (NF-𝜅B) pathways as well as significantly increased the expression of anti-inflammatory proteins. Conclusions : These results suggest that URW not only reduces oxidative stress through excellent antioxidant activity but also relieves gastric mucosal inflammation as a regulator of Nrf2 and NF-𝜅B pathways.
Hyun Ju Cha;Won Sik Eum;Gi Soo Youn;Jung Hwan Park;Hyeon Ji Yeo;Eun Ji Yeo;Hyun Jung Kwon;Lee Re Lee;Na Yeon Kim;Su Yeon Kwon;Yong-Jun Cho;Sung-Woo Cho;Oh-Shin Kwon;Eun Jeong Sohn;Dae Won Kim;Duk-Soo Kim;Yu Ran Lee;Min Jea Shin;Soo Young Choi
BMB Reports
/
v.56
no.4
/
pp.234-239
/
2023
Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H2O2-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury.
Purpose: In this study, we investigated anti-thrombotic effects of Gamihyunbooleekyungtang currently used clinical treatment of dysmenorrhea and compared effects by decoction methods. Methods: Gamihyunbooleekyungtang was extracted by pressure extractor (GHYT) and nonpressure extractor(GHYT-1). Inhibitory effect of platelet cohesion, suppression effect of GPIIb/IIIa activity, inhibitory effect of $TXB_2$ and $PEG_2$ biosynthesis, and oxidative damage suppression effect were tested in vitro. Also suppression of pulmonary embolism was studied in vivo. Results: In this study, both GHYT and GHYT-1 extract showed a safety in cytotoxicity of hFCs. Both showed dose-dependent inhibitory effect on platelet coagulation. GHYT-1 extract is usually higher than GHYT, especially for $E_{max}$. GHYT and GHYT-1 extract showed dose-dependent inhibitory effect on GPIIb/IIIa activities. GHYT extract suppressed significantly $TXB_2$ biosynthesis at 1000, $500{\mu}g/m{\ell}$ and also suppressed significantly $PEG_2$ biosynthesis at $1000{\mu}g/m{\ell}$ as compared with the control group. GHYT-1 suppressed significantly $TXB_2$ biosynthesis at $1000{\mu}g/m{\ell}$ as compared with the control group. Also it suppressed pulmonary embolism triggered by collagen and epinephrine by respectively 50%, 75% as compared with the control group. Both GHYT and GHYT-1 extract showed dose-dependent decrease of oxidative damages caused by DPPH, whereas dose-dependent increase of superoxide dismutase like activity was observed. Conclusion: These results suggest that Gamihyunbooleekyungtang can be used for treating dysmenorrhea caused by thrombosis. Nonpressure decoction method is a little more effective, but more detailed studies would be needed.
Gastritis is an inflammation of the gastric mucosa and gastric ulcers are a break in the mucosa of the stomach lining. Past research on gastritis and gastric ulcers has been mainly conducted from the perspective that environmental factors are the primary cause of these gastric diseases. However, recently the importance of genetic factors has been emphasized due to current developments in genetic research. The SLC25A26 gene is believed to be associated with the accumulation of reactive oxygen species. Oxidative stress promotes an inflammatory response, which increases the production of free radicals and causes cellular damage, and these lead to the development of gastric diseases. In this study, the correlation between SLC25A26 and gastric diseases was analyzed. Polymorphisms in SLC25A26 were analyzed in 1,369 domestic gastric disease patients and 7,471 healthy controls. As a result, 11 single nucleotide polymorphisms (SNPs) (in the genotype) and 13 SNPs (in the imputation) showed statistical significance (P<0.05), and high relative risk of gastric diseases. Among them, the rs13874 allele of SLC25A26 showed a highly significant association with gastric diseases. In the genotype-based mRNA expression analysis, the minor allele (C) group showed increased mRNA expression and this could increase oxidative stress. In conclusion, SLC25A26 polymorphisms are associated with gastric diseases. These results may provide a basis for new guidelines for gastric disease management in the Korean population.
Journal of the Korean Society of Food Science and Nutrition
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v.33
no.2
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pp.455-462
/
2004
Prostate cancer is a leading cause of cancer death in American men and evidences point to significant life style/diet components as risk factors for its development or prevention. Two large cohort studies have identified the consumption of tomatoes or high Plasma levels of Iycopene as associated with reduced risk. A number of other substances such as quercetin, phytoene, phytofluene, cyclolycopene, salicylates and tomatine in tomato besides lycopene could have anticancer activity and may be acting synergistically with lycopene. Lycopene at almost physiologically feasible concentrations, reduces cell viability by cell cycle arrest and apoptosis and modulates the cyclin pathways as well as increasing intercellular communication. However, it is not clear whether lycopene or its oxidation products are more bioactive. Tomato product supplementation results in plasma accumulation of phytoene, Phytofluene, the lycopene oxidation product, and cyclolycopene at significant concentrations and lycopene supplementation, either as a tomato product or as beadlets, results in maximal mean plasma lycopene concentrations of ∼ 1 $\mu$M which is at the lower limit of its activity in cell culture. Rats and mice are poor accumulators of lycopene and other carotenoids making them poor models for the study of cancer prevention and control. Of the 19 animal studies for various cancer sites, lycopene showed a positive effect in 10 studies but negative in 2 prostate cancer studies. In vivo prevention of leukocyte DNA damage in humans has been mostly studied using tomato product supplementation but lycopene supplementation appeared to reduce oxidative DNA damage as well as tomato product supplementation. Lycopene appears to be bioactive in intefering with carcinogenesis but the actions of phytoene, phytofluene or cyclolycopene cannot be ruled out since these compounds were present in most of the lycopene material used for these studies. Although lycopene remains as a promising agent, especially for cancer control, exploring interactions with other tomato phytochemicals and with current prostate cancer therapies should be encouraged.
Journal of the Korean Society of Food Science and Nutrition
/
v.42
no.3
/
pp.378-383
/
2013
The purpose of this study is to evaluate the antioxidant activities of extracts from Acer tegmentosum Maxim. (AT) and the ability of these extracts to reduce the serum alcohol concentration in rats administered alcohol. The total amount of polyphenols in hot water and ethanol extracts from AT were $71.93{\pm}2.2{\mu}g/mg$ and $152.69{\pm}1.25{\mu}g/mg$, respectively, while the total amount of flavonoids in hot water and ethanol extracts from AT were $7.51{\pm}1.34{\mu}g/mg$ and $5.01{\pm}0.83{\mu}g/mg$, respectively. FRAP values in AT extracts were $1.67{\sim}1.75{\mu}M/{\mu}g$. AT extracts were capable of directly scavenging DPPH and ABTS free radicals, with higher inhibitory activities for TBA. The hepatoprotective effect of hot water extracts from AT against ethanol-induced oxidative damage was investigated. Ethanol-induced damage on HepG2 liver cells were protected by hot water extracts from AT. Administration of hot water extracts from AT (200 mg/kg) had reduced serum alcohol levels in acute alcohol-treated rats. These results indicate that AT extracts can be protective against alcohol-induced toxicity, potentially through its antioxidant properties.
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