Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
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Inhibitory Effect of Cynaroside Isolated from Lonicera japonia Thunb on Doxorubicin-induced Necrosis in Human Renal Proximal Tubular HK-2 Cells

인동덩굴로부터 분리된 Cynaroside이 Doxorubicin으로 유도된 인간 근위세뇨관 HK-2 세포의 괴사에 미치는 저해 효과

  • Nho, Jong Hyun (National Development Institute of Korean Medicine) ;
  • Jung, Ho Kyung (National Development Institute of Korean Medicine) ;
  • Lee, Mu Jin (National Development Institute of Korean Medicine) ;
  • Jang, Ji Hun (National Development Institute of Korean Medicine) ;
  • Sim, Mi Ok (National Development Institute of Korean Medicine) ;
  • Jung, Ja Kyun (National Development Institute of Korean Medicine) ;
  • Jung, Da Eun (National Development Institute of Korean Medicine) ;
  • An, Byeong Kwan (National Development Institute of Korean Medicine) ;
  • Cho, Hyun Woo (National Development Institute of Korean Medicine)
  • Received : 2017.08.22
  • Accepted : 2017.10.16
  • Published : 2017.10.30
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Abstract

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

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