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昆明植物所在雷公藤紅素抵抗肝損傷研究中取得新進展

文章來源:昆明植物研究所   發布時間:2019-03-22  【字號:     】  

  雷公藤紅素(Celastrol)是從中藥雷公藤(Tripterygium Wilfordi)中分離得到的一種三萜類化學成分。研究證明Celastrol具有抗炎、抗癌的作用,還可以抑制多種腫瘤細胞的增殖、發生、發展以及遷移。2007年,Celastrol被Cell雜志列為最有可能發展為藥物的五種天然產物之一。最近還報道Celastrol具有較好的抵抗肥胖的作用。因此,Celastrol的活性及機制研究備受國內外研究機構的關注。

  中國科學院昆明植物研究所天然藥物化學前沿交叉團隊李飛研究組長期關注于核受體與重大疾病的藥物研發。最近發現Celastrol顯著降低膽汁淤積性肝損傷模型的炎癥反應,恢復膽汁酸代謝的動態平衡,從而治療膽汁淤積性的肝損傷。應用代謝組學方法進一步揭示Celastrol通過調節SIRT1-FXR信號通路發揮肝保護作用。并與昆明醫科大學第二附屬醫院、云南省第一人民醫院合作,證實Celastrol可以通過調節SIRT1-FXR信號通路來抵抗膽汁淤積性肝損傷。當機體發生膽汁淤積性肝損傷時,不但膽汁酸代謝發生紊亂,而且脂質代謝也異常。研究組采用脂質組學方法發現Celastrol可以調節多種脂類化合物的代謝,例如鞘磷脂和磷脂酰乙醇胺,它對脂質代謝的調節作用也依賴于FXR受體的表達水平。這表明Celastrol有望開發作為治療膽汁淤積性肝病的藥物。上述研究結果發表論文兩篇,其中以Celastrol Protects from Cholestatic Liver Injury through Modulation of SIRT1-FXR Signaling 為題發表在Molecular & Cellular Proteomics 雜志上,博士生趙琦為該文章的第一作者,李飛與唐映梅為共同通訊作者。另外,以Modulation of Lipid Metabolism by Celastrol 為題發表在Journal of Proteome Research 雜志上,碩士生張婷及博士生趙琦為該文章的第一作者,李飛為該文章的通訊作者。該研究得到特色所服務項目、西部之光B類項目等的支持。

  文章鏈接:1 2

 

圖1 Celastrol抵抗ANIT誘導的膽汁淤積性肝損傷

 

圖2 Celastrol抵抗膽汁淤積性肝病的機制




(責任編輯:葉瑞優)

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