4.7 Article

Naturally-derived diterpenoid sphaeropsidin C as an activator of Nrf2/ARE pathway and its potential capability of relieving intracellular oxidative stress in human lung epithelial cells

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 121, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2019.109669

Keywords

Sphaeropsidin C; Diterpenoid; Nrf2; Oxidative stress

Funding

  1. National Natural Science Foundation of China [81874341, 81673558]
  2. Young Scholars Program of Shandong University [2015WLJH50]

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Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway. Our data indicated that SC was able to stimulate Nrf2-mediated defensive system through promoting Nrf2 translocation, inhibiting Nrf2 ubiquitination, and enhancing Nrf2 stability in normal human lung epithelial Beas-2B cells. Furthermore, SC-induced Nrf2 activation required the involvement of protein kinases, exemplified by protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It alleviated sodium arsenite [As(III)]-induced intracellular oxidative stress in an Nrf2-dependent manner. These results suggested that SC displayed potential application for the prevention and therapy against oxidative stress-induced diseases. Moreover, isopimarane-type diterpenoid represents a promising skeleton for developing Nrf2 activators.

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