Dual Anti-oxidative Effects of Fraxetin Isolated from Fraxinus rhinchophylla

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概要

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• Atherosclerosis is main cause of arteriosclerosis. The pivotal role of low-density lipoprotein (LDL) oxidation in atherogenesis suggests antioxidants may help prevent cardiovascular disease. Fraxinus rhynchophylla DENCE (Oleaceae) is a traditional medicinal plant from East Asia. During the course of characterizing potential drug candidates from natural products, we isolated two major coumarins, esculetin and fraxetin and found that fraxetin has dual-antioxidative functions. Low concentrations (1—5 μM) of fraxetin potently inhibited LDL oxidation induced by metal and free radicals. Moreover, treatment of vascular smooth muscle cells (VSMCs) with higher concentrations (above 30 μM) of fraxetin significantly increased the protein level of heme oxygenase-1 (HO-1), a key enzyme that inhibits vascular proliferation and atherosclerosis. Subcellular fractionation and reporter gene analysis using an antioxidant response element (ARE) construct revealed that fraxetin increased the level of nuclear factor (NF)-E2-related factor 2 (Nrf2) and reporter activity, and these were associated with the induction of antioxidant enzymes, such as HO-1 and glutathione S-transferase-α. In conclusion, fraxetin has direct protective properties against LDL oxidation at lower concentrations, and higher concentrations of fraxetin induce antioxidant enzymes via Nrf2/ARE activation. These effects suggest potential anti-atherosclerosis effects of Fraxinus rhynchophylla D.

• 日本薬学会の論文

著者

• BAE KiHwan

  College of Pharmacy, Chungnam National University

• Kang Keon

  Bk21 Project Team Chosun University : College Of Pharmacy Chosun University

• KIM Sang

  College of Veterinary Medicine, Chungnam National University

• Bae Kihwan

  College Of Pharmacy Chungnam National University

• Kim Sang

  College Of Pharmacy Seoul National University

• Pokharel Yuba

  Bk21 Project Team Chosun University : College Of Pharmacy Chosun University

• Thuong Phuong

  BK21 Project Team, College of Pharmacy, Chosun University

• Lee Moo

  College of Pharmacy, Chonnam National University

• Su Nguyen

  College of Pharmacy, Chungnam National University

• Oh Won

  BK21 Project Team, College of Pharmacy, Chosun University

• Kang Keon

  Bk21 Project Team Chosun University

• Su Nguyen

  College Of Pharmacy Chungnam National University

• Pokharel Yuba

  BK21 Project Team, College of Pharmacy, Chosun University

• Kang Keon

  BK21 Project Team, College of Pharmacy, Chosun University

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