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 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.