食品科学 ›› 2019, Vol. 40 ›› Issue (5): 156-161.doi: 10.7506/spkx1002-6630-20171109-105

• 营养卫生 • 上一篇    下一篇

p-辛弗林通过激活AMPK-FoxO1信号通路抑制肝细胞葡萄糖生成

郭莉霞1,2,张永红3,殷钟意1,2,蒲语涵1,郑旭煦1,2,*   

  1. 1.天然药物研究重庆高校市级重点实验室,重庆工商大学,重庆 400067;2.废油资源化技术与装备教育部工程研究中心,重庆工商大学,重庆 400067;3.重庆医科大学药学院,重庆 400016
  • 出版日期:2019-03-15 发布日期:2019-04-02
  • 基金资助:
    国家自然科学基金青年科学基金项目(81603173);重庆市科学技术委员会研究项目(cstc2018jcyjAX0754);重庆市教委科学技术研究项目(KJ1600607);重庆高校市级重点实验室开放课题(1456032)

p-Synephrine Suppresses Hepatic Glucose Production via the AMPK-FoxO1 Signaling Pathway in HepG2 Cells

GUO Lixia1,2, ZHANG Yonghong3, YIN Zhongyi1,2, PU Yuhan1, ZHENG Xuxu1,2,*   

  1. 1. Key Laboratory of Natural Medicine Research of Chongqing Education Commission, Chongqing Technology and Business University, Chongqing 400067, China; 2. Engineering Research Centre for Waste Oil Recovery Technology and Equipment, Ministry of Education, Chongqing Technology and Business University, Chongqing 400067, China; 3. College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
  • Online:2019-03-15 Published:2019-04-02

摘要: 目的:探讨p-辛弗林对肝细胞葡萄糖生成的影响及其作用机制。方法:采用MTS法检测p-辛弗林对HepG2肝细胞株的细胞活力的影响,确定受试物的作用浓度后,比色法测定葡萄糖的生成、葡萄糖-6-磷酸酶(glucose-6-phosphatase,G6Pase)和磷酸烯醇丙酮酸羧基激酶(phosphoenolpyruvate carboxykinase,PEPCK)活力,Western blot蛋白印迹法检测腺苷酸活化蛋白激酶(adenosine 5’-monophosphate-activated protein kinase,AMPK)、磷酸化AMPK(p-AMPK)、乙酰辅酶A羧化酶(acetyl coenzyme A synthetase,ACC)、磷酸化ACC(p-ACC)、叉头框转录因子1(forkhead box class O1,FoxO1)以及磷酸化FoxO1(p-FoxO1)的表达;利用AMPK选择性抑制剂Compound C和AMPK siRNA作用HepG2肝细胞株后,检测p-辛弗林对HepG2肝细胞株葡萄糖的生成、G6Pase和PEPCK活力的影响。结果:p-辛弗林能剂量依赖性地抑制肝细胞葡萄糖的生成,激活AMPK信号通路,促进p-AMPK、p-ACC和p-FoxO1水平增加,极显著抑制G6Pase和PEPCK的活性(P<0.01)。p-辛弗林的这些影响部分地被Compound C和AMPK siRNA所抑制(P<0.01)。结论:p-辛弗林能够通过激活AMPK-FoxO1信号通路抑制肝细胞葡萄糖生成。

关键词: p-辛弗林, 腺苷酸活化蛋白激酶信号通路, 葡萄糖生成

Abstract: Objective: This study was designed to determine the effect of p-synephrine, the primary protoalkaloid of bitter orange and other citrus species, on hepatic glucose production in HepG2 cells and to elucidate the underlying mechanisms. Methods: The cell viability was detected by MTS assay. Glucose production and the activity of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were measured by colorimetry. The protein expression levels of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), acetyl coenzyme A synthetase (ACC), phosphorylated ACC (p-ACC), forkhead box class O1 (FoxO1) and phosphorylated FoxO1 (p-FoxO1) were analyzed by Western blot. The cells were incubated in the presence of selective AMPK inhibitor Compound C or AMPK siRNA to examine the impact of p-synephrine on glucose production and G6Pase and PEPCK activity. Results: p-Synephrine significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, ACC and FoxO1 phosphorylation were stimulated by different concentrations of p-synephrine. In addition, both enzyme activities were significantly suppressed (P < 0.01). These effects were partially reversed by Compound C and AMPK siRNA. Conclusion: p-Synephrine suppresses hepatic glucose production via the AMPK-FoxO1 signaling pathway in HepG2 cells.

Key words: p-synephrine, adenosine 5’-monophosphate-activated protein kinase signaling pathway, glucose production

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