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  2. The inhibitory effect in Fraxinellone on oxidative stress-induced senescence correlates with AMP-activated protein kinase-dependent autophagy restoration

The inhibitory effect in Fraxinellone on oxidative stress-induced senescence correlates with AMP-activated protein kinase-dependent autophagy restoration

  • J Cell Physiol. 2018 May;233(5):3945-3954. doi: 10.1002/jcp.26169.
Xiaojuan Han 1 Honghan Chen 1 Jiao Zhou 1 Haoran Tai 1 Hui Gong 1 Xiaobo Wang 1 Ning Huang 1 Jianqiong Qin 1 Tingting Fang 1 Fei Wang 2 Hengyi Xiao 1
Affiliations

Affiliations

  • 1 Lab for Aging Research, Center of Gerontology and Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
  • 2 Key Laboratory of Natural Medicine and Clinical Translation, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
Abstract

As a natural metabolite of limonoids from Dictamnus dasycarpus, fraxinellone has been reported to be neuroprotective and anti-inflammatory. However, its influence on cellular metabolism remains largely unknown. In the present study, we investigated the effect of fraxinellone on cellular senescence-induced by oxidative stress and the potential mechanism. We found that fraxinellone administration caused growth arrest and certainly repressed the activity of senescence associated β-galactosidase as well as the expression of senescence-associated-genes. Interestingly, this effect of fraxinellone is closely correlated with the restoration of impaired Autophagy and the activation of AMPK. Notably, fraxinellone reacts in an AMPK-dependent but mTORC1-independent manner. Together, our study demonstrates for the first time that fraxinellone has the effect on senescence inhibition and AMPK activation, and supports the notion that autophagic mechanism is important for aging prevention. These findings expanded the list of natural compounds and will be potentially utilized for aging decay and/or AMPK activation.

Keywords

AMPK; autophagy; fraxinellone; oxidative stress; senescence.

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