ArticlePharmaceutics2023
The Neuroprotective Effects of Flavonoid Fisetin against Corticosterone-Induced Cell Death through Modulation of ERK, p38, and PI3K/Akt/FOXO3a-Dependent Pathways in PC12 Cells.
Article in Pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- PI3K-Akt signaling network crosstalk in cerebral ischemia/reperfusion injury: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Pharmacological mechanisms of fisetin in neurodegenerative disorders: regulation of neuroinflammatory, oxidative, and autophagic pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Flavonoids extract fromWorld journal of experimental medicine · 2025Review
- Fisetin alleviates oxidative stress and promotes porcine early embryonic development via activation of the NRF2-ARE signalling pathway.Animal bioscience · 2025Article
- Targeting mitochondria with natural polyphenols for treating Neurodegenerative Diseases: a comprehensive scoping review from oxidative stress perspective.Journal of translational medicine · 2025Article
- Fisetin: hormesis accounts for many of its chemoprotective effects.Biogerontology · 2025Review
- Corticosterone effects induced by stress and immunity and inflammation: mechanisms of communication.Frontiers in endocrinology · 2025Review
- Prevention of high-fat/high-sugar diet-induced type 2 diabetes mellitus-associated non-alcoholic fatty liver disease in rats with fermented and raw Rosa roxburghii Tratt (Cili) juice.Frontiers in nutrition · 2025Article
- Preparation and Characterization of Small-Size and Strong Antioxidant Nanocarriers to Enhance the Stability and Bioactivity of Curcumin.Foods (Basel, Switzerland) · 2024Article
- Fisetin attenuates AlClToxicology reports · 2024Article
- Fisetin reduces ovalbumin-triggered airway remodeling by preventing phenotypic switching of airway smooth muscle cells.Respiratory research · 2024Article
- Fisetin enhances cisplatin sensitivity in renal cell carcinoma via the CDK6/PI3K/Akt/mTOR signaling pathway.Oncology letters · 2024Article
- The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The overactive hypothalamic-pituitary-adrenal (HPA) axis is believed to trigger the overproduction of corticosterone, leading to neurotoxicity in the brain. Fisetin is a flavonoid commonly found in fruits and vegetables. It has been suggested to possess various biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. This study aims to explore the potential neuroprotective properties of fisetin against corticosterone-induced cell death and its underlying molecular mechanism in PC12 cells. Our results indicate that fisetin, at concentrations ranging from 5 to 40 μM, significantly protected PC12 cells against corticosterone-induced cell death. Fisetin effectively reduced the corticosterone-mediated generation of reactive oxygen species (ROS) in PC12 cells. Fisetin treatments also showed potential in inhibiting the corticosterone-induced apoptosis of PC12 cells. Moreover, inhibitors targeting MAPK/ERK kinase 1/2 (MEK1/2), p38 MAPK, and phosphatidylinositol 3-kinase (PI3K) were found to significantly block the increase in cell viability induced by fisetin in corticosterone-treated cells. Consistently, fisetin enhanced the phosphorylation levels of ERK, p38, Akt, and c-AMP response element-binding protein (CREB) in PC12 cells. Additionally, it was found that the diminished levels of p-CREB and p-ERK by corticosterone can be restored by fisetin treatment. Furthermore, the investigation of crosstalk between ERK and CREB revealed that p-CREB activation by fisetin occurred through the ERK-independent pathway. Moreover, we demonstrated that fisetin effectively counteracted the corticosterone-induced nuclear accumulation of FOXO3a, an apoptosis-triggering transcription factor, and concurrently promoted FOXO3a phosphorylation and its subsequent cytoplasmic localization through the PI3K/Akt pathway. In conclusion, our findings indicate that fisetin exerts its neuroprotective effect against corticosterone-induced cell death by modulating ERK, p38, and the PI3K/Akt/FOXO3a-dependent pathways in PC12 cells. Fisetin emerges as a promising phytochemical for neuroprotection.
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