Targeting PI3K/AKT signaling pathway in obesity

Savova, Martina S.; Mihaylova, Liliya; Tews, Daniel; Wabitsch, Martin; Georgiev, Milen I.

doi:10.1016/j.biopha.2023.114244

Cited by 36 publications

(6 citation statements)

References 147 publications

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“…Results from the KEGG enrichment analysis (Fig. 4(J–L); Supporting Information, Table S3) revealed that processed PK may combat hyperglycemia via regulating multiple pathways – that is, AGE‐RAGE, 31 PI3K‐Akt, 32 MAPK, 33 insulin 34 and FoxO 35 signaling. The activation of AGE‐RAGE signaling has been shown to cause oxidative stress and inflammatory response, consequently leading to vascular complications in diabetic animal models 36 .…”

Section: Resultsmentioning

confidence: 99%

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

Zhou,

Liu,

Yan

et al. 2023

J Sci Food Agric

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BACKGROUNDPolygonatum kingianum Coll. & Hemsl (PK), a prominent medicine and food homology plant, has been consumed as a decoction from boiling water for thousands of years. 'Nine Steaming Nine Sun‐drying' processing has been considered an effective method for enriching tonic properties, but studies investigating such impacts on PK and underlying mechanisms are extremely rare.RESULTSWe first demonstrated substantial improvements in the anti‐oxidative, anti‐inflammatory and anti‐hyperglycemia effects of the Nine Steaming Nine Sun‐drying processed PK water extracts compared with crude PK in cell models (i.e., HepG2 and Raw 264.7 cells). We then integrated foodomics and network pharmacology analysis to uncover the key compounds responsible for the improved benefits. A total of 551 metabolites of PK extracts were identified, including polyphenols, flavonoids, alkaloids, and organic acids. During processing, 204 metabolites were enhanced, and 32 metabolites were recognized as key constituents of processed PK responsible for the improved health‐promoting activities, which may affect PI3K‐Akt‐, MAPK‐, and HIF‐1 pathways. We further confirmed the high affinity between identified key constituents of processed PK and their predicted acting targets using molecular docking.CONCLUSIONOur results provide novel insights into bioactive compounds of processed PK, elaborating the rationality of processing from the perspective of tonic effects. Consuming processed PK could be an efficacious strategy to combat the high prevalence of metabolic diseases that currently affect millions of people worldwide. © 2023 Society of Chemical Industry.

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Section: Resultsmentioning

confidence: 99%

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

Zhou,

Liu,

Yan

et al. 2023

J Sci Food Agric

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“…Akt, the downstream of PI3K, is a key regulator of many cellular responses including protein synthesis, gene transcription, cell survival, proliferation, and differentiation [42]. And PI3K/Akt pathway regulates mechanically driven and receptorligand signaling [43]. The activation of eNOS can be triggered by the activation of protein kinase Akt and phosphoinositide-3-kinase (PI3K) [44].…”

Section: Discussionmentioning

confidence: 99%

Protective effects of phosphocreatine on human vascular endothelial cells against hydrogen peroxide-induced apoptosis and in the hyperlipidemic rat model

Tang

Zhang

Wang

et al. 2023

Preprint

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Phosphocreatine (PCr) has been shown to have a cardio-protective effect during cardiopulmonary resuscitation (CPR). However, little is known about its impact on atherosclerosis. In this study, we firstly evaluated the pharmacological effects of PCr on antioxidative defenses and mitochondrial protection against hydrogen peroxide (H2O2) induced human umbilical vascular endothelial cells (HUVECs) damage. Then we investigated the hypolipidemic and antioxidative effects of PCr on hyperlipidemic rat model. Via in vitro studies, H2O2 significantly reduced cell viability and increased apoptosis rate of HUVECs, while pretreatment with PCr abolished its apoptotic effect. PCr could reduce the generation of ROS induced by H2O2. Moreover, PCr could increase the activity of SOD and the content of NO, as well as decrease the activity of LDH and the content of MDA. PCr could also antagonize H2O2-induced up-regulation of Bax, cleaved-caspase3, cleaved-caspase9, and H2O2-induced down-regulation of Bcl-2 and p-Akt/Akt ratio. In addition, PCr reduced U937 cells’ adhesion to H2O2-stimulated HUVECs. Via in vivo study, PCr could decrease MDA, TC, TG and LDL-C levels in hyperlipidemic rats. Finally, different-concentration PCr could increase the leaching of TC, HDL, and TG from fresh human atherosclerotic plaques. In conclusion, PCr could suppress H2O2-induced apoptosis in HUVECs and reduce hyperlipidemia through inhibiting ROS generation and modulating dysfunctional mitochondrial system, which might be an effective new therapeutic strategy to further prevent atherosclerosis.

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“…Overactivation of the IGF‐1/PI3K/AKT/mTORC1 axis resulting from overnutrition provokes inflammation (Savova et al., 2023). Correspondingly, a chronic low‐grade inflammatory state is part of the vicious cycle that is formed in obesity, diabetes, and obesity‐related metabolic disorders that positively correlate with aging (Vasileva et al., 2018).…”

Section: “New” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Todorova,

Savova,

Mihaylova

et al. 2024

Food Frontiers

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The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

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Targeting PI3K/AKT signaling pathway in obesity

Cited by 36 publications

References 147 publications

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

Protective effects of phosphocreatine on human vascular endothelial cells against hydrogen peroxide-induced apoptosis and in the hyperlipidemic rat model

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

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