Puerarin inhibits amyloid β-induced NLRP3 inflammasome activation in retinal pigment epithelial cells via suppressing ROS-dependent oxidative and endoplasmic reticulum stresses

Journal Article · Tue Aug 15 04:00:00 EDT 2017 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2017.05.030· OSTI ID:22738148

Wang, Ke ^[1]; Zhu, Xue; Zhang, Kai ^[1]; Yao, Yong ^[2]; Zhuang, Miao; Tan, Chengye ^[2]; Zhou, Fanfan ^[3]; Zhu, Ling ^[4]

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1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine. Wuxi 214063, Jiangsu Province (China)
2. Department of Ophthalmology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu Province (China)
3. Faculty of Pharmacy, University of Sydney, NSW 2006 (Australia)
4. Save Sight Institute, University of Sydney, NSW 2000 (Australia)

Amyloid β (Aβ) is a critical stimulator that promotes the progression of age-related macular degeneration (AMD). NLRP3 inflammasome activation induced by Aβ is estimated to be responsible for retinal pigment epithelium (RPE) dysfunction in such disease. Puerarin, one of the major active constituents of Kudzu root, has been widely used in the clinical treatment of AMD in China for decades; however, the detailed molecular mechanism remains far from clear. In this study, we investigated the protective effect and underlying mechanism of puerarin against Aβ{sub 1–40}-induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells. The results showed that Aβ{sub 1–40} induced NLRP3 inflammasome activation mainly via triggering ROS-dependent oxidative stress, particularly lipid peroxidation, and endoplasmic reticulum stress in LPS-primed ARPE-19 cells; however, such effect could be significantly reversed by puerarin in a dose-dependent manner. Furthermore, the effect of puerarin was potentially mediated through activating Nrf2/HO-1 antioxidant signaling pathway and inhibiting Aβ{sub 1–40}-induced phosphorylation of IRE1 and PERK as well as nuclear expression of ATF6α. Therefore, the significance of the current study is to reveal the novel mechanism of puerarin in the prevention of AMD. - Highlights: • Puerarin attenuates Aβ{sub 1-40}-induced NLRP3 inflammasome activation in ARPE-19 cells. • Puerarin attenuates NLRP3 inflammasome activation via suppressing ROS-dependent oxidative and endoplasmic reticulum stresses. • The protective effect of puerarin is mediated through activating Nrf2/HO-1 and inhibiting IRE1/PERK/ATF6 signaling pathways.

• OSTI ID: 22738148
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 357; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL STRESS
ENDOPLASMIC RETICULUM
INHIBITION
OXIDATION
RHODOPSIN
STRESSES