HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

Tammaro, Alessandra; Daniels, Eileen G.; Hu, Iman M.; ‘t Hart, Kelly C.; Reid, Kim; Juni, Rio P.; Butter, Loes M.; Vasam, Goutham; Kamble, Rashmi; Jongejan, Aldo; Aviv, Richard I.; Roelofs, Joris J.T.H.; Aronica, Eleonora; Boon, Reinier A.; Menzies, Keir J.; Houtkooper, Riekelt H.; Janssens, Georges E.

doi:10.1016/j.isci.2023.108681

Cited by 3 publications

(3 citation statements)

References 64 publications

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“…The organ index is an important macro-index used to evaluate the health status of organs [ 43 ]. When the organ declines due to damage, the organ’s index will decrease, which is also combined with organ failures [ 44 ]. In this study, QE treatment significantly decreases the organ index of the brain, liver, and kidneys, caused by the D-gal treatment, indicating that QE treatment could dramatically relieve the atrophy of the brain, liver, and kidneys in D-gal-treated mice.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway

Wang,

Zhao

et al. 2024

Molecules

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Que Zui tea (QT) is an important herbal tea in the diet of the ‘Yi’ people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6′-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1β and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6′-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway

Wang,

Zhao

et al. 2024

Molecules

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“…Therefore, piperlongumine has been shown to epigenetically promote cell proliferation through inhibition of both expression and activity of histone deacetylase 1 (HDAC1) . This enzyme, which is a key repressor of cell cycle progression, − has been reported to be overexpressed during aging and to promote senescence, while its pharmacological inhibition leads to in vivo aging-protective effects in mice …”

Section: Introductionmentioning

confidence: 99%

“…A panel of compounds with known health-beneficial properties has been tested for their capacity to induce FOXO factors activity and to prevent senescence. Among the natural products evaluated, piperlongumine was shown to stimulate FOXO-dependent transcription through activation of its nuclear translocation . While the mechanism involved is still unclear, data suggested that it is independent of the PI3K/AKT pathway and the CRM1-mediated nuclear export.…”

Section: Introductionmentioning

confidence: 99%

Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases

Dotou,

L’honoré,

Moumné

et al. 2024

J. Nat. Prod.

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Nature is an important source of bioactive compounds and has continuously made a large contribution to the discovery of new drug leads. Particularly, plant-derived compounds have long been identified as highly interesting in the field of aging research and senescence. Many plants contain bioactive compounds that have the potential to influence cellular processes and provide health benefits. Among them, Piper alkaloids have emerged as interesting candidates in the context of age-related diseases and particularly senescence. These compounds have been shown to display a variety of features, including antioxidant, anti-inflammatory, neuroprotective, and other bioactive properties that may help counteracting the effects of cellular aging processes. In the review, we will put the emphasis on piperlongumine and other related derivatives, which belong to the Piper alkaloids, and whose senomodulating potential has emerged during the last several years. We will also provide a survey on their potential in therapeutic perspectives of age-related diseases.

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Epigenetic modifications and emerging therapeutic targets in cardiovascular aging and diseases

Qiu,

Xu,

Xie

et al. 2025

Pharmacological Research

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HDAC1/2 inhibitor therapy improves multiple organ systems in aged mice

Cited by 3 publications

References 64 publications

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway

Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases

Epigenetic modifications and emerging therapeutic targets in cardiovascular aging and diseases

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