Activation of the miR-34a-Mediated SIRT1/mTOR Signaling Pathway by Urolithin A Attenuates d-Galactose-Induced Brain Aging in Mice

Chen, Peng; Chen, Fuchao; Lei, Jiexin; Li, Qiaoling; Zhou, Benhong

doi:10.1007/s13311-019-00753-0

Cited by 153 publications

(122 citation statements)

References 41 publications

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“…The in vivo D-galactose-induced brain aging model showed that urolithin A significantly suppressed the upregulation of miR-34a induced by D-galactose. The overall conclusion was that urolithin A may have neuroprotective effects, especially in preventing D-gal-induced brain aging through the activation of the miR-34a-mediated SIRT1/mTOR signaling pathway [53].…”

Section: Urolithin Activity In the Modulation Of Oxidative Stressmentioning

confidence: 99%

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Djedjibegović

Marjanović

Panieri³

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a state of excess of prooxidative species relative to the antioxidant defenses (enzymatic and nonenzymatic) in a living organism. The consequence of this imbalance is damage of the major cellular macromolecules (carbohydrates, lipids, proteins, and DNA), which further leads to a gradual loss of tissue and organ function. It has been shown that oxidative stress plays an important role in the pathogenesis of many chronic diseases (cardiovascular, metabolic, and neurodegenerative diseases and cancer) and in the process of aging. Thus, many strategies to combat oxidative stress have been proposed and tested. In this context, food rich in antioxidants has received great attention. Pomegranate, berries, and walnuts have been recognized as “superfood” particularly for their cardioprotective effects. The common characteristic of these foods is the high content of ellagitannins. Since tannins are not bioavailable, they have been neglected in nutrition science and even considered antinutrients for a long time. However, this view has changed dramatically once it was recognized that ellagic acid, released from ellagitannins in the gastrointestinal system, is further metabolized by colonic microbiota to bioavailable compounds—known as urolithins. Thus, urolithins (3,4-benzocoumarin derivatives) have emerged as novel natural bioactive compounds and are now the focus of extensive investigations. So far, urolithins were shown to be powerful modulators of oxidative stress and agents with potential anti-inflammatory, antiproliferative, and antiaging properties. Furthermore, a few synthetic derivatives of urolithins were recognized as lead compounds for new drug development. Available data on urolithin synthesis, physicochemical and pharmacokinetic characteristics, biological activity, and safety will be presented in this review.

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Section: Urolithin Activity In the Modulation Of Oxidative Stressmentioning

confidence: 99%

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Djedjibegović

Marjanović

Panieri³

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…glucose deprivation, cytoprotective drugs and genetic suppression of inflammasome activity) act to simultaneously up-regulate SIRT1/PGC-1α and suppresses the Akt/mTOR pathway. 20 , 91–93 Furthermore, drugs that act to directly up-regulate SIRT1 (e.g. resveratrol and SIRT1 activators) also serve to inhibit Akt/mTOR, 85 , 94–98 and conversely, suppression of SIRT1 leads to up-regulation of Akt/mTOR.…”

Section: Sirt1 and Akt/mtor Signalling In The Regulation Of Organismamentioning

confidence: 99%

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Packer

2020

European Heart Journal

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The two primary molecular regulators of lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). Each plays a central role in two highly interconnected pathways that modulate the balance between cellular growth and survival. The activation of SIRT1 [along with peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) and adenosine monophosphate-activated protein kinase (AMPK)] and the suppression of mTORC1 (along with its upstream regulator, Akt) act to prolong organismal longevity and retard cardiac ageing. Both activation of SIRT1/PGC-1α and inhibition of mTORC1 shifts the balance of cellular priorities so as to promote cardiomyocyte survival over growth, leading to cardioprotective effects in experimental models. These benefits may be related to direct actions to modulate oxidative stress, organellar function, proinflammatory pathways, and maladaptive hypertrophy. In addition, a primary shared benefit of both SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 inhibition is the enhancement of autophagy, a lysosome-dependent degradative pathway, which clears the cytosol of dysfunctional organelles and misfolded proteins that drive the ageing process by increasing oxidative and endoplasmic reticulum stress. Autophagy underlies the ability of SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 suppression to extend lifespan, mitigate cardiac ageing, alleviate cellular stress, and ameliorate the development and progression of cardiomyopathy; silencing of autophagy genes abolishes these benefits. Loss of SIRT1/PGC-1α/AMPK function or hyperactivation of Akt/mTORC1 is a consistent feature of experimental cardiomyopathy, and reversal of these abnormalities mitigates the development of heart failure. Interestingly, most treatments that have been shown to be clinically effective in the treatment of chronic heart failure with a reduced ejection fraction have been reported experimentally to exert favourable effects to activate SIRT1/PGC-1α/AMPK and/or suppress Akt/mTORC1, and thereby, to promote autophagic flux. Therefore, the impairment of autophagy resulting from derangements in longevity gene signalling is likely to represent a seminal event in the evolution and progression of cardiomyopathy.

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“…Uro-A regulates the expression of intercellular adhesion factor-1 via the ERK/peroxisome proliferator activated receptor-γ signaling pathway, which exerts anti-inflammatory effects (39). Uro-A also induces mitophagy, prolongs the lifespan of Caenorhabditis elegans and increases muscle function in rodents (40,41). In the present study, it was speculated that uro-A was the active component that induced the antioxidant effect of cassia seeds (12,42).…”

Section: Discussionmentioning

confidence: 70%

Metabolite identification of gut microflora‑cassia seed interactions using UPLC‑QTOF/MS

et al. 2020

Exp Ther Med

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Cassia seed is the dried ripe seed of Cassia obtusifolia L. or Cassia tora L., which is widely used as a food or traditional Chinese medicine. The aim of the present study was to detect the components and metabolites in the culture of human or rat intestinal microflora suspension with the water decoction of cassia seed in vitro, using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry system equipped with a negative ion scan mode. Initially, ellagic acid was identified in the cassia seed decoction. Subsequently, six different metabolites, including urolithin (uro)-A, uro-B, uro-D, uro-M6, uro-M7 and uro-B-glucuronide (glur), were detected after co-culture of the cassia seed decoction with intestinal microflora, but not in the cassia seed decoction alone. Uro-M6, uro-M7, uro-A and uro-B were common metabolites in the culture of human or rat intestinal microflora suspension with the water decoction of cassia seed. However, uro-D was only detected in the culture of rat intestinal microflora suspension with the water decoction of cassia seed, and uro-B-glur was only detected in the culture of human intestinal microflora with the water decoction of cassia seed. The uro and intermediate metabolites were produced by ellagic acid in the cassia seed decoction under the action of the intestinal microflora. The production of metabolites might be related to the abundance and diversity of the intestinal microflora in humans and rats. The present study provided rationale for further pharmacological and clinical studies on the mechanisms of action of cassia seeds.

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Activation of the miR-34a-Mediated SIRT1/mTOR Signaling Pathway by Urolithin A Attenuates d-Galactose-Induced Brain Aging in Mice

Cited by 153 publications

References 41 publications

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Metabolite identification of gut microflora‑cassia seed interactions using UPLC‑QTOF/MS

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