Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling

(1) Background: Various epidemiological studies suggest that oxidative stress and disrupted neuronal function are mechanistically linked to neurodegenerative diseases (NDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). DNA damage, oxidative stress, lipid peroxidation, and eventua...

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Main Authors: Betul Cicek, Sidika Genc, Yesim Yeni, Mehmet Kuzucu, Ahmet Cetin, Serkan Yildirim, Ismail Bolat, Mecit Kantarci, Ahmet Hacimuftuoglu, Georgios Lazopoulos, Aristidis Tsatsakis, Konstantinos Tsarouhas, Ali Taghizadehghalehjoughi
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Journal of Personalized Medicine
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Online Access:https://www.mdpi.com/2075-4426/12/12/2012
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author Betul Cicek
Sidika Genc
Yesim Yeni
Mehmet Kuzucu
Ahmet Cetin
Serkan Yildirim
Ismail Bolat
Mecit Kantarci
Ahmet Hacimuftuoglu
Georgios Lazopoulos
Aristidis Tsatsakis
Konstantinos Tsarouhas
Ali Taghizadehghalehjoughi
author_facet Betul Cicek
Sidika Genc
Yesim Yeni
Mehmet Kuzucu
Ahmet Cetin
Serkan Yildirim
Ismail Bolat
Mecit Kantarci
Ahmet Hacimuftuoglu
Georgios Lazopoulos
Aristidis Tsatsakis
Konstantinos Tsarouhas
Ali Taghizadehghalehjoughi
author_sort Betul Cicek
collection DOAJ
description (1) Background: Various epidemiological studies suggest that oxidative stress and disrupted neuronal function are mechanistically linked to neurodegenerative diseases (NDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). DNA damage, oxidative stress, lipid peroxidation, and eventually, cell death such as NDs can be induced by nitrosamine-related compounds, leading to neurodegeneration. A limited number of studies have reported that exposure to diethylnitrosamine (DEN), which is commonly found in processed/preserved foods, causes biochemical abnormalities in the brain. Artichoke leaves have been used in traditional medicine as a beneficial source of bioactive components such as hydroxycinnamic acids, cynarine, chlorogenic acid, and flavonoids (luteolin and apigenin). The aim of this study is to investigate the favorable effects of exogenous artichoke (Cynara scolymus) methanolic leaf extract supplementation in ameliorating DEN-induced deleterious effects in BALB/c mouse brains. (2) Methods: This study was designed to evaluate DEN (toxicity induction by 100 mg/kg) and artichoke (protective effects of 0.8 and 1.6 g/kg treatment) for 14 days. All groups underwent a locomotor activity test to evaluate motor activity. In brain tissue, oxidative stress indicators (TAC, TOS, and MDA), Klotho and PPARγ levels, and apoptotic markers (Bax, Bcl-2, and caspase-3) were measured. Brain slices were also examined histopathologically. (3) Results: Artichoke effectively ameliorated DEN-induced toxicity with increasing artichoke dose. Impaired motor function and elevated oxidative stress markers (decreasing MDA and TOS levels and increasing TAC level) induced by DEN intoxication were markedly restored by high-dose artichoke treatment. Artichoke significantly improved the levels of Klotho and PPARγ, which are neuroprotective factors, in mouse brain tissue exposed to DEN. In addition, caspase-3 and Bax levels were reduced, whereas the Bcl-2 level was elevated with artichoke treatment. Furthermore, recovery was confirmed by histopathological analysis. (4) Conclusions: Artichoke exerted neuroprotective effects against DEN-induced brain toxicity by mitigating oxidant parameters and exerting antioxidant and antiapoptotic effects. Further research is needed to fully identify the favorable impact of artichoke supplementation on all aspects of DEN brain intoxication.
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spelling doaj.art-fdf067311e4242919b079743db0e28b12023-11-24T16:02:07ZengMDPI AGJournal of Personalized Medicine2075-44262022-12-011212201210.3390/jpm12122012Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ SignalingBetul Cicek0Sidika Genc1Yesim Yeni2Mehmet Kuzucu3Ahmet Cetin4Serkan Yildirim5Ismail Bolat6Mecit Kantarci7Ahmet Hacimuftuoglu8Georgios Lazopoulos9Aristidis Tsatsakis10Konstantinos Tsarouhas11Ali Taghizadehghalehjoughi12Department of Physiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum 25240, TurkeyDepartment of Biology, Faculty of Arts and Sciences, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Biology, Graduate School of Natural and Applied Sciences, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, TurkeyDepartment of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, TurkeyDepartment of Radiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum 25240, TurkeyDepartment of Cardiac Surgery, University General Hospital of Heraklion, Medical School, University of Crete, 71003 Heraklion, GreeceDepartment of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, GreeceDepartment of Cardiology, University General Hospital of Larissa, 41110 Larissa, GreeceDepartment of Medical Pharmacology, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, Turkey(1) Background: Various epidemiological studies suggest that oxidative stress and disrupted neuronal function are mechanistically linked to neurodegenerative diseases (NDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). DNA damage, oxidative stress, lipid peroxidation, and eventually, cell death such as NDs can be induced by nitrosamine-related compounds, leading to neurodegeneration. A limited number of studies have reported that exposure to diethylnitrosamine (DEN), which is commonly found in processed/preserved foods, causes biochemical abnormalities in the brain. Artichoke leaves have been used in traditional medicine as a beneficial source of bioactive components such as hydroxycinnamic acids, cynarine, chlorogenic acid, and flavonoids (luteolin and apigenin). The aim of this study is to investigate the favorable effects of exogenous artichoke (Cynara scolymus) methanolic leaf extract supplementation in ameliorating DEN-induced deleterious effects in BALB/c mouse brains. (2) Methods: This study was designed to evaluate DEN (toxicity induction by 100 mg/kg) and artichoke (protective effects of 0.8 and 1.6 g/kg treatment) for 14 days. All groups underwent a locomotor activity test to evaluate motor activity. In brain tissue, oxidative stress indicators (TAC, TOS, and MDA), Klotho and PPARγ levels, and apoptotic markers (Bax, Bcl-2, and caspase-3) were measured. Brain slices were also examined histopathologically. (3) Results: Artichoke effectively ameliorated DEN-induced toxicity with increasing artichoke dose. Impaired motor function and elevated oxidative stress markers (decreasing MDA and TOS levels and increasing TAC level) induced by DEN intoxication were markedly restored by high-dose artichoke treatment. Artichoke significantly improved the levels of Klotho and PPARγ, which are neuroprotective factors, in mouse brain tissue exposed to DEN. In addition, caspase-3 and Bax levels were reduced, whereas the Bcl-2 level was elevated with artichoke treatment. Furthermore, recovery was confirmed by histopathological analysis. (4) Conclusions: Artichoke exerted neuroprotective effects against DEN-induced brain toxicity by mitigating oxidant parameters and exerting antioxidant and antiapoptotic effects. Further research is needed to fully identify the favorable impact of artichoke supplementation on all aspects of DEN brain intoxication.https://www.mdpi.com/2075-4426/12/12/2012DENartichokeoxidative stressapoptosisKlothoPPARγ
spellingShingle Betul Cicek
Sidika Genc
Yesim Yeni
Mehmet Kuzucu
Ahmet Cetin
Serkan Yildirim
Ismail Bolat
Mecit Kantarci
Ahmet Hacimuftuoglu
Georgios Lazopoulos
Aristidis Tsatsakis
Konstantinos Tsarouhas
Ali Taghizadehghalehjoughi
Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
Journal of Personalized Medicine
DEN
artichoke
oxidative stress
apoptosis
Klotho
PPARγ
title Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
title_full Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
title_fullStr Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
title_full_unstemmed Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
title_short Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
title_sort artichoke cynara scolymus methanolic leaf extract alleviates diethylnitrosamine induced toxicity in balb c mouse brain involvement of oxidative stress and apoptotically related klotho pparγ signaling
topic DEN
artichoke
oxidative stress
apoptosis
Klotho
PPARγ
url https://www.mdpi.com/2075-4426/12/12/2012
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