Camphorquinone Promotes the Antisenescence Effect via Activating AMPK/SIRT1 in Stem Cells and D-Galactose-Induced Aging Mice.

Nagarajan Maharajan,Gwang-Won Cho

doi:10.3390/antiox10121916

Abstract

Terpenoids are a wide class of secondary metabolites with geroprotective properties that can alter the mechanism of aging and aging-related diseases. Camphorquinone (CQ) is a bicyclic monoterpenoid compound that can be efficiently synthesized through the continuous bromination and oxidation reaction of camphor. The purpose of this study is to investigate the effects of CQ on oxidative-stress-induced senescence and its underlying mechanisms. To generate oxidative stress in human bone marrow mesenchymal stem cells (hBM-MSCs) and mice, we used hydrogen peroxide (200 μM twice) and D-galactose (D-Gal) (150 mg/kg for 10 weeks), respectively. Our findings suggest that CQ potentially reduces senescence in hBM-MSCs and mouse heart tissue. In addition, we found that CQ boosted AMPK/SIRT1 activation and autophagy in both models. These results were subsequently verified in hBM-MSCs using compound C (an AMPK inhibitor) but AMPK inhibition by CC did not significantly reduce the SIRT1 and the autophagy markers. CQ treatment also reduced the gene expression of inflammation markers in D-Gal-induced aging mouse heart tissue. Furthermore, we determined that CQ fits all of the pharmacological parameters using the freely available SwissADME Web tool. Collectively, our findings demonstrate that CQ possesses antisenescence and cardioprotective properties, and that oxidative-stress-induced senescence could be suppressed by AMPK/SIRT1 and autophagy mechanisms.

Highlights

Published: 29 November 2021Cellular senescence is a state of persistent cell cycle arrest that is considered to be a hallmark of aging [1,2,3]
Oxidative stress is a type of stress-induced premature senescence (SIPS) that can be utilized to investigate the mechanism of cellular senescence both in vitro and in vivo [8,9,10,11]
We evaluated the effect of CQ on oxidative-stress-induced senescence, as described previously [11]

Summary

Introduction

Cellular senescence is a state of persistent cell cycle arrest that is considered to be a hallmark of aging [1,2,3]. Researchers are searching for new therapeutic medications or targets to eradicate or reduce the negative consequences of these senescent cells while animals age [6,7]. Oxidative stress is a type of stress-induced premature senescence (SIPS) that can be utilized to investigate the mechanism of cellular senescence both in vitro and in vivo [8,9,10,11]. Activation of AMPK, SIRT1, and autophagy mechanisms has been shown to prevent oxidative-stress-induced senescence [11,12,13]. To alleviate oxidative-stress-induced senescence and aging, a novel medication or compound that can activate AMPK, SIRT1, and autophagy is required

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