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  2. Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms

Carnosol as a Nrf2 Activator Improves Endothelial Barrier Function Through Antioxidative Mechanisms

  • Int J Mol Sci. 2019 Feb 18;20(4):880. doi: 10.3390/ijms20040880.
Xi Li 1 2 Qiao Zhang 3 4 Ning Hou 5 6 Jing Li 7 8 Min Liu 9 10 Sha Peng 11 12 Yuxin Zhang 13 14 Yinzhen Luo 15 16 Bowen Zhao 17 18 Shifeng Wang 19 20 Yanling Zhang 21 22 Yanjiang Qiao 23 24
Affiliations

Affiliations

  • 1 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. xixili1994@163.com.
  • 2 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. xixili1994@163.com.
  • 3 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhangqiao0824@foxmail.com.
  • 4 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. zhangqiao0824@foxmail.com.
  • 5 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. 13821117290@163.com.
  • 6 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. 13821117290@163.com.
  • 7 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. lijing20171008@163.com.
  • 8 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. lijing20171008@163.com.
  • 9 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. liumin_94@163.com.
  • 10 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. liumin_94@163.com.
  • 11 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. moonshadow0406@163.com.
  • 12 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. moonshadow0406@163.com.
  • 13 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhangyuxinwjzy@163.com.
  • 14 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. zhangyuxinwjzy@163.com.
  • 15 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. lyz985472@163.com.
  • 16 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. lyz985472@163.com.
  • 17 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhaobw9504@163.com.
  • 18 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. zhaobw9504@163.com.
  • 19 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. alana6268@126.com.
  • 20 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. alana6268@126.com.
  • 21 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. zhangyanling@bucm.edu.cn.
  • 22 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. zhangyanling@bucm.edu.cn.
  • 23 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. yjqiao@bucm.edu.cn.
  • 24 Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China. yjqiao@bucm.edu.cn.
Abstract

Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of Lactate Dehydrogenase (LDH) as well as Reactive Oxygen Species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.

Keywords

HMVEC cells; antioxidant activity; carnosol; microvascular endothelial protection.

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