Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the <scp>PI3K</scp>/Akt/<scp>TERT</scp> pathway

Zhu, Lin; Liu, Zhenchao; Ren, Yuqian; Wu, Xiaolin; Liu, Yingjuan; Wang, Tingting; Li, Yizhao; Cong, Yu‐Sheng; Guo, Yunliang

doi:10.1002/ptr.7235

Cited by 23 publications

(16 citation statements)

References 50 publications

(57 reference statements)

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“…Accumulated evidence indicated that extracts of Rhodiola Rosea L. or salidroside reversed DNA damage and altered the expression of cytokines and antioxidative enzymes induced by ROS [ 40 ]. Studies have shown that salidroside can reverse hypoxia injury in PC12 cells by mitochondrial protection via inhibiting oxidative stress events [ 41 ], salidroside promoted telomerase reverse transcriptase protein expression via the PI3K/Akt pathway, and maybe a therapeutic strategy for aging-related disease treatment [ 42 ]. Our results showed that salidroside increased the viability of Glu-injured HT22 cells and alleviate the cognitive impairment induced by Aβ 1−42 .…”

Section: Discussionmentioning

confidence: 99%

Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells

et al. 2022

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Background Alzheimer’s disease (AD) is a neurodegenerative disease. Ferroptosis plays a critical role in neurodegenerative diseases. Nuclear factor E2-related factor 2 (Nrf2) is considered an important factor in ferroptosis. Studies have demonstrated that salidroside has a potential therapeutic effect on AD. The intrinsic effect of salidroside on ferroptosis is unclear. The purpose of this study was to investigate the protective effects and pharmacological mechanisms of salidroside on alleviating neuronal ferroptosis in Aβ1−42-induced AD mice and glutamate-injured HT22 cells. Methods HT22 cells were injured by glutamate (Glu), HT22 cells transfected with siRNA Nrf2, and Aβ1−42-induced WT and Nrf2−/−AD mice were treated with salidroside. The mitochondria ultrastructure, intracellular Fe2+, reactive oxygen species, mitochondrial membrane potential, and lipid peroxidation of HT22 cells were detected. Malondialdehyde, reduced glutathione, oxidized glutathione disulfide, and superoxide dismutase were measured. The novel object recognition test, Y-maze, and open field test were used to investigate the protective effects of salidroside on Aβ1−42-induced WT and Nrf2−/−AD mice. The protein expressions of PTGS2, GPX4, Nrf2, and HO1 in the hippocampus were investigated by Western blot. Results Salidroside increased the cell viability and the level of MMP of Glu-injured HT22 cells, reduced the level of lipid peroxidation and ROS, and increased GPX4 and SLC7A11 protein expressions. These changes were not observed in siRNA Nrf2 transfected HT22 cells. Salidroside improved the ultrastructural changes in mitochondria of HT22 cells and Aβ1−42-induced AD mice, but not in Aβ1−42-induced Nrf2−/−AD mice. Salidroside increased protein expression levels of GPX4, HO1, and NQO1 and decreased protein expression of PTGS2 in Aβ1−42-induced AD mice but not in Aβ1−42-induced Nrf2−/−AD mice. Conclusions Salidroside plays a neuroprotective role by inhibiting neuronal ferroptosis in Aβ1−42-induced AD mice and Glu-injured HT22 cells, and its mechanism is related to activation of the Nrf2/HO1 signaling pathway. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells

et al. 2022

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“…Meanwhile, a 25-mg/kg/day for 8-week gavaging treatment profoundly improved cognition dysfunction in aged mice and alleviated neuronal degeneration in the aging mice hippocampal CA1 region. Further evaluation of the treated mice suggested that salidroside promotes telomerase reverse transcriptase expression via the PI3K/Akt pathway ( 62 ).…”

Section: Bbb Is a Challenging Boundary For Most Phytochemical Drugs W...mentioning

confidence: 99%

The Phytochemical Potential for Brain Disease Therapy and the Possible Nanodelivery Solutions for Brain Access

Liu

Chen

et al. 2022

Front. Oncol.

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Plant-derived phytochemicals have gifted humans with vast therapeutic potentials. Yet, the unique features of the blood–brain barrier significantly limit their accession to the target tissue and thus clinical translation in brain disease treatment. Herein, we explore the medicinal outcomes of both the rare examples of phytochemicals that can easily translocate across the blood–brain barrier and most of the phytochemicals that were reported with brain therapeutic effects, but a bizarre amount of dosage is required due to their chemical nature. Lastly, we offer the nanodelivery platform that is capable of optimizing the targeted delivery and application of the non-permeable phytochemicals as well as utilizing the permeable phytochemicals for boosting novel applications of nanodelivery toward brain therapies.

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“…Hypomethylation of the promoters of p16 INK4A and p21 CIP1/WAF1 , two cell-cycle inhibitors and senescence markers, may play a role in cellular senescence and aging. In naturally aging mouse models or human tissues, the increased level of p21 and p16 proteins in the old group as compared to the young group was observed [ 62 , 63 ]. It was experimentally determined that the cause of such an increase was due to the reduced methylation of the promoter regions of the genes.…”

Section: The Signaling Pathways Associated With Neuronal Senescence and Brain Agingmentioning

confidence: 99%

Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging

et al. 2021

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With an increased life expectancy among humans, aging has recently emerged as a major focus in biomedical research. The lack of in vitro aging models—especially for neurological disorders, where access to human brain tissues is limited—has hampered the progress in studies on human brain aging and various age-associated neurodegenerative diseases at the cellular and molecular level. In this review, we provide an overview of age-related changes in the transcriptome, in signaling pathways, and in relation to epigenetic factors that occur in senescent neurons. Moreover, we explore the current cell models used to study neuronal aging in vitro, including immortalized cell lines, primary neuronal culture, neurons directly converted from fibroblasts (Fib-iNs), and iPSC-derived neurons (iPSC-iNs); we also discuss the advantages and limitations of these models. In addition, the key phenotypes associated with cellular senescence that have been observed by these models are compared. Finally, we focus on the potential of combining human iPSC-iNs with genome editing technology in order to further our understanding of brain aging and neurodegenerative diseases, and discuss the future directions and challenges in the field.

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Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the PI3K/Akt/TERT pathway

Cited by 23 publications

References 50 publications

Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells

Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells

The Phytochemical Potential for Brain Disease Therapy and the Possible Nanodelivery Solutions for Brain Access

Human iPSC-Derived Neurons as A Platform for Deciphering the Mechanisms behind Brain Aging

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