亚洲传统医药 ›› 2020, Vol. 15 ›› Issue (5): 239-254.

• Regular Article • 上一篇    下一篇

Main alkaloids of Rhizoma Coptidis improved palmitic acidinduced insulin resistance in HepG2 cells via AMPK and MAPK signaling pathway

Ming Qu 1, #, Ying Wang 4, #, Shijie Cao 2, Yalu Liu 1, Da Liu 1, Feng Qiu 3,*, Ning Kang 1,*   

  1. 1 Department of Biochemistry, School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 2 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 3 School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 4 Faculty of Life Sciences and Biological Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
  • 收稿日期:2020-07-31 修回日期:2020-09-22 接受日期:2020-09-22 出版日期:2020-10-20 发布日期:2020-10-30

Main alkaloids of Rhizoma Coptidis improved palmitic acidinduced insulin resistance in HepG2 cells via AMPK and MAPK signaling pathway

Ming Qu 1, #, Ying Wang 4, #, Shijie Cao 2, Yalu Liu 1, Da Liu 1, Feng Qiu 3,*, Ning Kang 1,*   

  1. 1 Department of Biochemistry, School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 2 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 3 School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 4 Faculty of Life Sciences and Biological Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
  • Received:2020-07-31 Revised:2020-09-22 Accepted:2020-09-22 Online:2020-10-20 Published:2020-10-30
  • Contact: Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China; Tel.:18920189618, 18622871485; E-mail: kangndd@163.com (N. Kang), fengqiu20070118@163.com (F. Qiu.). E-mail:kangndd@163.com;fengqiu20070118@163.com

摘要: Rhizoma Coptidis, a traditional Chinese herbal medicine, has been used for treating diabetes for thousands of years. However, the molecular basis for this action has not been elucidated. In the present study, the effects of seven main alkaloids of Rhizoma Coptidis on glycometabolism were investigated and the related molecular mechanism of five active compounds on insulin resistant (IR) cell model was explored for the first time. Results showed that berberine, palmatine, epiberberine, columbamine and groenlandicine enhanced glucose consumption in the palmitic acid (PA)-induced IR-HepG2 cells, indicating that these compounds could improve IR. In addition, we found that among these active alkaloids, berberine, columbamine, epiberberine and groenlandicine could inhibit the activation of ERK and p38 pathway, while berberine, columbamine, palmatine and epiberberine could activate AMPK pathway. Moreover, palmatine and columbamine regulated the mRNA expression of GLUT2 to ameliorate IR via activating AMPK and inactivating p38 MAPK signal pathway. To sum up, berberine, columbamine, palmatine, epiberberine and groenlandicine might be the active reagents, which contribute to the glucose lowering effects of Rhizoma Coptidis.

关键词: Rhizoma Coptidis, alkaloids, insulin resistance, AMPK pathway, MAPK pathway, GLUT2

Abstract: Rhizoma Coptidis, a traditional Chinese herbal medicine, has been used for treating diabetes for thousands of years. However, the molecular basis for this action has not been elucidated. In the present study, the effects of seven main alkaloids of Rhizoma Coptidis on glycometabolism were investigated and the related molecular mechanism of five active compounds on insulin resistant (IR) cell model was explored for the first time. Results showed that berberine, palmatine, epiberberine, columbamine and groenlandicine enhanced glucose consumption in the palmitic acid (PA)-induced IR-HepG2 cells, indicating that these compounds could improve IR. In addition, we found that among these active alkaloids, berberine, columbamine, epiberberine and groenlandicine could inhibit the activation of ERK and p38 pathway, while berberine, columbamine, palmatine and epiberberine could activate AMPK pathway. Moreover, palmatine and columbamine regulated the mRNA expression of GLUT2 to ameliorate IR via activating AMPK and inactivating p38 MAPK signal pathway. To sum up, berberine, columbamine, palmatine, epiberberine and groenlandicine might be the active reagents, which contribute to the glucose lowering effects of Rhizoma Coptidis.

Key words: Rhizoma Coptidis, alkaloids, insulin resistance, AMPK pathway, MAPK pathway, GLUT2