Neuroprotective effect of tangeretin against chromium-induced acute brain injury in rats: targeting Nrf2 signaling pathway, inflammatory mediators, and apoptosis

Abstract

Potassium dichromate (PD) is an environmental xenobiotic commonly recognized as teratogenic, carcinogenic, and mutagenic in animals and humans. The present study was conducted to investigate the role of tangeretin (TNG) as a neuro-protective drug against PD-induced brain injury in rats. Thirty-two male adult Wistar rats were blindly divided into four groups (8 rats/group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally), for 14 days followed by i.n. of PD on the last day of the experiment. The fourth group received TNG (100 mg/kg; orally) for 14 days followed by i.n. of PD on the last day of the experiment. Behavioral indices were evaluated 18 h after PD administration. Neuro-biochemical indices and histopathological studies were evaluated 24 h after PD administration. Results of the present study revealed that rats intoxicated with PD induced- oxidative stress and inflammation via an increase in malondialdehyde (MDA) and a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and glutathione(GSH) levels with an increase in brain contents of tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6). Pre-treatment with TNG (100 mg/kg; orally) ameliorated behavior, cholinergic activities, and oxidative stress and decreased the elevated levels of pro-inflammatory mediators; TNF-α and IL-6 with a decrease in brain content of chromium residues detected by Plasma–Optical Emission Spectrometer. Also, the histopathological picture of the brain was improved significantly in rats that received TNG (100 mg/kg). Additionally, TNG decreased caspase-3 expression in the brain of PD rats. In conclusion, TNG possesses a significant neuroprotective role against PD-induced acute brain injury via modulating the Nrf2 signaling pathway and quenching the release of inflammatory mediators and apoptosis in rats. Graphical abstract

Novel Targets for Chronic Inflammatory Diseases: Focus On Therapeutic Drugs and Natural Compounds, volume II

“…Tangeretin (Tan) is a naturally occurring flavonoid mainly found in the peel peel of citrus plants. It exhibits various pharmacological properties, such as antioxidant and antiinflammatory effects (Xin, et al, 2019;Sedik and Elgohary, 2023).Tan is absorbed by the gastrointestinal tract and primarily metabolized to 4′-demethyltangeretin by CYP1A1 and CYP1A2 enzymes (Surichan et al, 2018). Tan has the potential to mitigate acute lung injury induced by LPS through the inhibition of the Th17 response, TNF-α, and MPO activity via the Notch signaling pathway (M. Li, Zhao, Qi, et al, 2020).…”

An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders

“…In a recent study, the effect of TAN on brain injury induced by chromium was evaluated [108]. Potassium dichromate, a xenobiotic, was administered to Wistar rats and the neuroprotective potential of TAN was explored.…”

“…Life 2024, 14, x FOR PEER REVIEW 13 of 24 significantly reversed the potassium-dichromate-induced alterations in behavior and cholinergic activities. The authors suggest that the mechanism involved in the potential neuroprotective benefits exhibited by TAN might be the regulation of the Nrf2 and caspase-3 signaling pathways [108]. A schematic diagram of the possible signaling pathways involved in the neuroprotective benefits of TAN is shown in Figure 4.…”

Tangeretin attenuates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition via the PI3K/Akt pathway

“…Tangeretin (Tan) is a naturally occurring flavonoid mainly found in the peel peel of citrus plants. It exhibits various pharmacological properties, such as antioxidant and anti-inflammatory effects ( Xin, et al, 2019 ; Sedik and Elgohary, 2023 ).Tan is absorbed by the gastrointestinal tract and primarily metabolized to 4′-demethyltangeretin by CYP1A1 and CYP1A2 enzymes ( Surichan et al, 2018 ). Tan has the potential to mitigate acute lung injury induced by LPS through the inhibition of the Th17 response, TNF-α, and MPO activity via the Notch signaling pathway (M. Li, Zhao, Qi, et al, 2020 ).…”