• Title/Summary/Keyword: Inhibition of nitric oxide

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Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways

  • Kim, Sung Hwan;Lee, In Chul;Ko, Je Won;Moon, Changjong;Kim, Sung Ho;Shin, In Sik;Seo, Young Won;Kim, Hyoung Chin;Kim, Jong Choon
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.180-188
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    • 2015
  • This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-${\kappa}B$), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-${\kappa}B$ and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

Evaluation of the In vitro Activity of Glycyrrhiza Cultivar Roots (감초 육성품종 뿌리 추출물의 In vitro 활성 평가)

  • Lee, Seung Eun;Lee, Jeong Hoon;Park, Chun Geon;Kim, Hyung Don;Lee, Yun Ji;Seo, Kyung Hae;Jeong, Hyeon Soo;Chang, Jae Ki;Kim, Dong Hwi
    • Korean Journal of Medicinal Crop Science
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    • v.27 no.2
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    • pp.115-125
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    • 2019
  • Background: Glycyrrhiza radix (licorice root) have been used as an oriental medicine material for long time, and its protective effects on oxidative stress, inflammation and cognition deficit have been recently reported. However, the cultivation of Glycyrrhiza species as medicinal crops is associated with some problems such as low productivity and early leaf fall, etc. To resolve this problems, Glycyrrhiza cultivars have been developed by direct hybridization of each Glycyrrhiza species by Korean researchers. The present study was conducted to compare the Glycyrrhiza cultivar radix (Dagam, Sinwongam and Wongam) for their anti-oxidation, anti-inflammation, and cognition improvement effects and levels of liquiritin, isoliquiritigenin and licochalcone in order to select an excellent cultivar as a material resource. Methods and Results: For evaluating the inhibitory efficacies of the Glycyrrhiza cultivar extracts on oxidative stress and inflammation in BV2 cells, we measured their reactive oxygen species (ROS) production and nitric oxide (NO) release after treating them with lipopolysccharide. The scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxynitrite ($NOO^-$) radicals were evaluated. Cell proliferation and N-methyl-D-aspartate receptor (NMDAR) inhibition were analyzed. The total phenol, liquiritin, isoliquiritigenin and licochalcone A content in the extracts of the three culivars were quantified. Furthermore, the correlation coefficient between the activities and contents of total phenol, liquiritin, isoliquiritigenin and licochalcone A were also calculated. The results indicated that Sinwongam exhibited potent anti-oxidant, anti-inflammatory and NMDAR inhibititory activities. Sinwongam also showed higher total phenol and licochalcone A contents than the other cultivars. Among the three cultivars, Dagam exhibited a positive effects on NO release inhibition, cell proliferation and contents of liquiritin and isoliquiritigenin. Conclusions: Sinwongam is expected to be the most useful resource as a functional material for anti-oxidation/anti-inflammation and cognition improvement among the three studied licorice cultivars.

Antioxidant, anti-cholinesterase, and inflammation inhibitory activities of fruiting bodies of Phallus impudicus var. impudicus L. (말뚝버섯 자실체의 항산화, 항콜린에스테라제 및 염증 저해 활성)

  • Yoon, Ki Nam;Lee, Tae Soo
    • Journal of Mushroom
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    • v.17 no.3
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    • pp.152-161
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    • 2019
  • Phallus impudicus var. impudicus L. is an edible mushroom that has long been used as folk medicine in China. The aim of this study was to evaluate the antioxidant, anti-cholinesterase, and inflammation inhibitory activities of a methanol extract of fruiting bodies of P. impudicus var. impudicus L. The extract exhibited good 1,1-diphenyl-2-picrylhydrazyl scavenging activity, excellent ferrous ion chelating activity, and moderate hydroxyl radical scavenging activity compared with BHT at 2.0 mg/ml. However, the reducing power of the extract was significantly lower than that the BHT positive control. Although the inhibitory activities of methanol extract on acetylcholinesterase and butyryl cholinesterase were significantly lower than the galanthamine positive control at the concentration tested, the inhibition of acetylcholinesterase and butyryl cholinesterase was 52.83% and 55.17%, respectively, at 1.0 mg/ml. The methanol extract also demonstrated excellent inhibition of inflammation-related activities, such as production of nitric oxide in lipopolysaccharide-induced RAW 264.7 macrophage cells and acute edema induced by administration of carrageenan on the hind paw of rats. The collective results suggest that the fruiting body of P. impudicus var. impudicus L. might be a good source of antioxidant, anti-cholinesterase, and anti-inflammation compounds.

Comparison of Anti-oxidative and Anti-inflammatory Effect of Atractylodes Interspecific Hybrid Cultivar Roots (삽주 육성품종 뿌리의 항산화 및 항염증 효과 비교)

  • Jeong, Hyeon Soo;Jeong, Jin Tae;Lee, Jeong Hoon;Park, Chun Geon;Choi, Je Hun;Jang, Gwi Yeong;Kim, Jang Wook;Chang, Jae Ki;Kim, Dong Hwi;Lee, Seung Eun
    • Korean Journal of Medicinal Crop Science
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    • v.26 no.5
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    • pp.391-400
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    • 2018
  • Background: Atractylodes radix is a well-known medicinal crop having many physiological effects. This study was conducted to select useful Atractylodes japonica ${\times}$ Atractylodes macrocephala (AJM) cultivars by comparing anti-oxidative and anti-inflammatory efficacies. Methods and Results: Seven extracts from AJM cultivars were used to treat lipopolysacchride (LPS)-treated BV2 cells, and the effects on cell viability and inhibition on reactive oxygen species (ROS) and nitric oxide (NO) production were analyzed. In vitro scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxynitrite ($NOO^-$) radicals were also investigated. Contents of total phenol, atractylenolide I, and atractylenolide III in the AJM extracts were measured using high performance liquid chromatography (HPLC) or spectrophotometry. The experiments show that none of the seven extracts was cytotoxic above 89.2% at $20-250{\mu}g/m{\ell}$. Extracts of Gowon, Dawon, Sangchul, and Huchul inhibited ROS generation in a dose-dependent manner, and Sangchul extract showed the highest inhibition on ROS production. All the AJM extracts showed effective inhibitory activity after on NO release in the LPS-treated BV2 cells, and Sangchul extract showed the highest activity. Sangchul extract had the most potent scavenging activities for $NOO^-$ and had some DPPH radical scavenging effect. Sangchul extract also had the highest content at total phenol and atractylenolide I content. Atractylenolide III was not detected in the AJM extracts. Conclusions: The results suggested that Sangchul was the most useful anti-oxidative and anti-inflammatory resource among the AJM cultivars.

Apoptotic Effect of Sasa quelpaertensis Nakai in Human Colon Cancer HT-29 Cells (인간 대장암 HT-29 세포에서 제주조릿대의 세포사멸 효과)

  • Byun, Ji Hee;Kim, Min Young
    • Journal of Life Science
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    • v.24 no.9
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    • pp.1012-1018
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    • 2014
  • Sasa quelpaertensis Nakai (Korean name, Jeju-Joritdae) is one of the most abundant plants on Mt. Halla, Jeju Island, and it has long been used in traditional medicines. Recent studies have reported it as possessing various beneficial functions, including anti-inflammatory, anti-diabetic, anti-hypertension, anti-gastritis, anti-oxidant, and anti-cancer effects. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In this study, we investigated the anti-cancer effects and mechanism of S. quelpaertensis on human colon cancer HT-29 cells. Cell growth inhibition by S. quelpaertensis was determined by MTT assay. Apoptosis was performed by DNA fragmentation, flow cytometry with propidium iodide staining (PI), and reverse transcription-polymerase chain reaction (RT-PCR) to confirm the anti-apoptotic factors, such as inhibitor of apoptosis (IAP) family members. $NO^{\bullet}$ production was determined by Griess assay. S. quelpaertensis treatment resulted in the time- and dose-dependent inhibition of the cell viability of HT-29 cells by inducing apoptosis, as evidenced by the accumulation of the sub-G1 cell population stained by PI, as well as the ladder-like DNA fragmentation in a dose-dependent manner. S. quelpaertensis-inducing apoptosis was accompanied by the induction of S cell cycle arrests, increasing $NO^{\bullet}$ concentrations, and the down-regulation of IAPs, including X-chromosome-linked IAP (XIAP), cellular IAP-1 (cIAP-1), cIAP-2, and survivin. Taken together, these findings have important implications for future clinical developments of S. quelpaertensis in colon cancer treatment.

Antioxidant and Anti-inflammatory Effects of Ethanol Extract of Aster yomena in RAW 264.7 Macrophages (RAW 264.7 대식세포에서 쑥부쟁이 추출물의 항산화 및 항염증 효능에 관한 연구)

  • Kim, Sung Ok;Jeong, Ji-Suk;Choi, Yung Hyun
    • Journal of Life Science
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    • v.29 no.9
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    • pp.977-985
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    • 2019
  • Aster yomena (Kitam.) Honda is an edible vegetable and perennial herb belonging to the Asteraceae family, and has been used for a long time for the prevention and treatment of various diseases. Although leaf extracts of A. yomena are known to have antioxidant and anti-inflammatory effects, accurate efficacy assessments are still inadequate. In this study, we investigated whether the antioxidant efficacy of ethanol extract of A. yomena leaf (EEAY) is correlated with the anti-inflammatory effect in RAW 264.7 macrophages. The results showed that EEAY significantly inhibited the hydrogen peroxide ($H_2O_2$)-induced growth inhibition in RAW 264.7 cells, which was associated with increased expression of nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1). EEAY pretreatment also effectively prevented $H_2O_2$-induced reactive oxygen species generation and apoptosis through inhibition of caspase-3 activation and poly (ADP-ribose) polymerase degradation. Additionally, EEAY significantly increased the expression and production of interleukin-10, a representative anti-inflammatory cytokine, which was associated with increased expression of toll-like receptor 4 and myeloid differentiation factor 88 at transcriptional and translational levels. Furthermore, the increased production of nitric oxide (NO) by lipopolysaccharide was markedly abolished under the condition of EEAY pretreatment, and the inhibitory effect of NO production by EEAY was further increased by hemin, an HO-1 inducer. Overall, our results suggest that EEAY is able to activate the Nrf2/HO-1 signaling pathway to protect RAW 264.7 macrophages from oxidative and inflammatory stress.

Evaluation of Biological Activity on The Hydrolyzable Tannins of Katsura Tree (Cercidiphyllum japonicum) (계수나무 가수분해형 탄닌의 생리활성 평가)

  • Min, Hee-Jeong;Lee, Min-Sung;Kim, Young-Kyoon;Bae, Young-Soo
    • Journal of the Korean Wood Science and Technology
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    • v.45 no.3
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    • pp.250-257
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    • 2017
  • Eight hydrolyzable tannin compounds, such as gallic acid (1), methyl gallate (2), kurigalin (3), 1,2,3,6-tetra-O-galloyl-${\beta}$-D-(+)-glucose (4), 1,2,3,4,6-penta-O-galloyl-${\beta}$-D-(+)-glucose (5), 6-m-digalloyl-1,2,3,4,6-penta-O-galloyl-${\beta}$-D-(+)-glucose (6), isocorilagin (7), macabarterin (8), were isolated from the EtOAc and $H_2O$ soluble fractions of Katsura tree (Cercidiphyllum japonicum) leaves, wood and bark. Then antioxidative and anti-inflammatory activity were evaluated on the each isolated compound. The antioxidative test was DPPH radical scavenging activity and all of the isolated compounds indicated much higher antioxidative values compare to the controls, BHT and ${\alpha}$-tocopherol. In the anti-inflammatory test measuring nitric oxide (NO) inhibition activity, methyl gallate, 1,2,3,6-tetra-O-galloyl-${\beta}$-D-glucose and 1,2,3,4,6-penta-O-galloyl-${\beta}$-D-glucose inhibited NO production, and especially, methyl gallate showed high inhibition activity. However, the anti-inflammatory activity of the hydrolyzable tannins did not show positive effect. Based on the above results, the hydrolyzable tannins of katsura tree may be used as one of the natural biomass sources that can substitute with the synthetic antioxidant.

Antioxidant and anti-inflammatory activities of Chrysanthemum indicum Linne extracts at different ethanol ratios (주정 농도별 감국 추출물의 항산화 및 항염증 활성)

  • Kang, Hyun;Park, Chan-Hwi;Kwon, Sang-Oh;Lee, Sung-Gyu
    • Korean Journal of Food Science and Technology
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    • v.53 no.4
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    • pp.416-422
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    • 2021
  • In the present study, antioxidant and anti-inflammatory activities were measured in Chrysanthemum indicum Linne extracted with different ethanol concentrations. The 50% ethanol extract demonstrated the highest yield of 33.6%, while the 30% and 70% ethanol extracts showed the highest total polyphenol contents of 59.70 and 61.35 mg GAE/g, respectively. The antioxidant activity of 70% ethanol extract was highest in the DPPH radical scavenging activity (RC50 14.95 ㎍/mL) and ABTS+ radical scavenging activity (RC50 42.28 ㎍/mL). FRAP activity was significantly higher in the 30% ethanol extract than the other extracts. The anti-inflammatory effects of Chrysanthemum indicum Linne extracted with different ethanol concentrations were examined using nitric oxide (NO) inhibition assays. In LPS-induced RAW 264.7 cells, the 30% ethanol extract showed the highest inhibition of NO production with 11.16 µM at a concentration of 200 ㎍/mL. The results of this study suggest that Chrysanthemum indicum extracted 30% or 70% ethanol concentrations as potential functional raw material.

Anti-Inflammatory Effect of Ligularia fischeri, Solidago virga-aurea and Aruncus dioicus Complex Extracts in Raw 264.7 Cells (곰취(Ligularia fischeri), 미역취(Solidago virga-aurea), 삼나물(Aruncus dioicus) 복합 추출물의 항염증 효과)

  • Kim, Dong-Hee;An, Bong-Jeun;Kim, Se-Gie;Park, Tae-Soon;Park, Gun-Hye;Son, Jun-Ho
    • Journal of Life Science
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    • v.21 no.5
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    • pp.678-683
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    • 2011
  • The objective of this study was to evaluate the skin inflammation effects of three herb mixture extracts, Ligularia fischeri, Solidago virga-aurea and Aruncus dioicus, which are from Ullung island in Korea. Regulatory mechanisms of cytokines and nitric oxide (NO) are involved in the immunological activity of Raw 264.7 cells. Tested cells were pretreated with 70% acetone extracts of Ligularia fischeri, Solidago virga-aurea and Aruncus dioicus (LSA-A) and further cultured for an appropriated time after lipopolyssacharide (LPS) addition. During the entire experimental period, 1, 10, and 100 ${\mu}g/ml$ of LSA-A had no cytotoxicity. In these concentrations, LSA-A inhibited the production of NO and prostaglandin $E_2$ ($PGE_2$), tumor necorsis factor-a (TNF-a), interleukin-1${\beta}$ (IL-1${\beta}$), interleukin-6 (IL-6) expression of inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2). LSA-A showed a 60% $PGE_2$ inhibition rate at 100 ${\mu}g/ml$. iNOS and COX-2 inhibition activities were 54%, and 65% at 100 ${\mu}g/ml$, respectively. In addition, LSA-A extract reduced the release of inflammatory cytokines including TNF-a, IL-1${\beta}$ and IL-6. These results suggest that LSA-A may have significant effects on inflammatory factors, and may be a potential anti-inflammatory therapeutic agent.

Total Phenolic Compound, Total Flavonoid Compound And Anti-Inflammatory Inhibitory Effects of Psidium Guajava Leaf Extract (구아바 잎 추출물의 총 폴리페놀과 플라보노이드 함량 및 항 염증 억제 효과)

  • Lee, Jeong-Seon;Kim, Chun-Dug
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.1
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    • pp.254-262
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    • 2018
  • It was intended to check a possibility of activity of Psidium guajava leaf extract as anti-oxidant and anti-inflammatory material. Total polyphenol and total flavonoid content of Psidium guajava leaf extract was checked. Cream having inhibitory effect on inflammation through toxicity and NO production inhibition in RAW 264.7 cell was manufactured, and skin safety was evaluated. It was confirmen that total polyphenol and flavonoid content of Psidium guajava leaf extract was 126.4 mg/g and 223.17 mg/g respectively, which was high content. According to the results of checking toxicity through cell viability in RAW 264.7 cell, cytotoxicity was not shown. And NO production indicating inflammatory disease was inhibited concentration-dependently. According to the results of carrying out single patch test after manufacturing the cream containing the Psidium guajava leaf extract, skin irritation did not occur for 24 h to put patch on skin or for 24 h after removing the patch. Putting these results together, it was verified that there was possibility of application as raw materials for cosmetics, which would have anti-oxidant activity owing to the high polyphenol and flavonoid content of Psidium guajava leaf extract and anti-inflammatory material through NO production inhibition.