• Title/Summary/Keyword: target gene FOXO3a

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Antioxidant Activity and Its Mechanism of Paeonia lactiflora Pall Extract

  • Heo, Jee-In;Kim, Jeong-Hyeon;Lee, Jeong-Min;Kim, Sung-Chan;Park, Jae-Bong;Kim, Jaebong;Lee, Jae-Yong
    • Natural Product Sciences
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    • v.19 no.1
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    • pp.49-53
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    • 2013
  • Paeonia lactiflora Pall (PL) has been used as a traditional herbal medicine in China, Korea, and Japan for more 1,200 years. PL has reported to have antioxidant activity and protective effect of cells from oxidative stress, although the mechanism has not been verified. FOXO3a is a transcription factor that binds to its target gene's consensus FOXO binding site. FOXO3a protein modulates the various biological functions including cell cycle control, apoptosis, DNA repair, and ROS detoxification. Therefore, FOXO3a activity is associated with cancer, aging, diabetes, infertility, neurodegeneration, and immune system dysfunction. Here we found that FOXO3a was activated by PL extract. Transcriptional target genes such as MnSOD, p27, and GADD45 were activated by PL extract. Protein levels of MnSOD and catalase were increased, consequently, ROS level was reduced in HEF cells by PL extract. These findings suggest that PL extract has an antioxidant activity through FOXO activation and thereby activation of FOXO target genes, MnSOD and catalase.

AntagomiR-27a Targets FOXO3a in Glioblastoma and Suppresses U87 Cell Growth in Vitro and in Vivo

  • Ge, Yun-Fei;Sun, Jun;Jin, Chun-Jie;Cao, Bo-Qiang;Jiang, Zhi-Feng;Shao, Jun-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.963-968
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    • 2013
  • Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells.

Protective Effects of Pyrrosiae Folium on the 2% Glucose-Induced Toxicity in Caenorhabditis elegans (석위가 예쁜꼬마선충에서 Glucose로 유도된 독성에 미치는 영향)

  • Kim, Bong Seok;Lee, Byung Ju;Lee, Hyun Joo;An, Soon Young;Park, Zi Won;Yoon, Seon Hwa;Oh, Mi Jin;Kwon, Jin;Lee, Se Youn;Cha, Dong Seok;Oh, Chan Ho;Jeon, Hoon
    • Korean Journal of Pharmacognosy
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    • v.48 no.3
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    • pp.179-186
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    • 2017
  • Pyrrosia lingua which belongs to Polypodiaceae has been used as a traditional medicine for the treatment of urinary system inflammation, urination disorder, and bronchitis. However, there are not enough phytochemical and pharmacological studies of P. lingua up to now. Here in this study, the protective effect of MeOH extract of whole plant of Pyrrosia lingua (MPL) against 2% glucose-induced toxicity was investigated using Caenorhabditis elegans (C. elegans) model system. We found that MPL significantly extended the lifespan of wild-type nematode under normal culture condition. MPL also effectively recovered the decreased lifespan caused by 2% glucose-toxicity. In addition, MPL efficiently attenuated the increased glucose concentration inside of nematode. Further studies evaluating diabetes-related factors revealed that MPL reduced both intracellular ROS and lipid accumulation which were up-regulated under 2% glucose supplement condition. Our data also showed that MPL improved the 2% glucose-induced shortened body movement of nematode. Lastly, we carried out genetic studies using several single gene knockout mutants to establish the possible target of MPL. Our results demonstrated that genes such as daf-2 and daf-16 were responsible for the protective activity of MPL against 2% glucose-induced toxicity. These results indicate that MPL exerts protective action against 2% glucose via regulation of insulin/IGF-1 sinaling pathway and FOXO activation.