Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress-induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 µM for double time) and D-galactose (D-Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow-mesenchymal stem cells (hBM-MSCs) and mice, respectively. We performed the SA-β-gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress-induced senescence by upregulating AMPK-mediated activation of autophagy in hBM-MSCs. D-Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti-senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress-induced senescence.

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.

High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein—an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.

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