The pathophysiology of diabetes-induced brain injury involves pyroptosis, an inflammatory programmed cell death. This study aimed to investigate the potential protective effect of cranberry extract (CE) against diabetes-induced brain injury. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin in rats. Brain tissue samples were investigated for biochemical determination of the reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), and the quantitative RT-PCR for the gene expression of glial cell-derived neurotrophic factor (GDNF), lncRNA GAS-5, and pyroptosis markers. ELISA was used to determine the caspase-1 level and immunohistochemical staining for assessing IL-1beta. Prophylactic dosing of the CE in diabetic rats improved cognitive behavior and significantly suppressed MDA concentration, pyroptosis genes expression (gasdermin D and caspase 1), and lncRNA GAS-5. In addition, CE significantly elevated GSH concentration, SOD activity, and gene expression of GDNF and markedly reduced IL-1beta positive stained cells score in the brain. Phytochemical characterization of the CE by FT-IR and UPLC-PDA-MS/MS revealed cyanidin arabinoside, procyanidins, quercetin, and isorhamnetin as key components. CE protects against diabetes-induced cognitive dysfunction in rats by targeting redox-related signaling pathways and inducing an anti-inflammatory effect. LncRNA GAS-5 downregulation and pyroptosis pathway inhibition may contribute to its beneficial effects, suggesting its therapeutic potential.

BACKGROUND: Cranberry (Vaccinium macrocarpon) is a small, red fruit that has been widely recognized for its potential health benefits. The cranberry is rich in antioxidant-rich bioactive chemicals and nutritious components like essential vitamins, minerals, and antioxidants; for example, vitamin C, vitamin E, magnesium, copper, potassium, anthocyanins, flavonoids, phenolic acid, etc. Cranberries are thought to offer a variety of health advantages because they are high in Polyphenols (PPs), which have significant antioxidant activity. 

OBJECTIVES: The objective of the current study was to evaluate the neuroprotective effect of cranberries on behavioural and neurochemical abnormalities induced by Quinolinic Acid (QA) treatment through Intracerebroventricular (ICV) injection in Wistar rats, as well as to identify the synaptic plasticity and cognition by modulating signaling cascades, such as the ERK and PI3K/AKT pathways, which offer an adjunct treatment to slow or enhance the effects of conventional treatment. 

MATERIAL AND METHODS: A total of thirty Wistar rats were randomly assigned to several experimental groups. QA (240 nM in normal saline) was administered via ICV. Thereafter, cranberry (0.5g/kg p.o.) with QA, and high-dose cranberry group (2g/kg p.o.) with QA were administered to the animals for 21 days. The dosage of QA and cranberries was chosen based on earlier experimental research. 

RESULT: The study found that cranberries significantly decrease cognitive deficits and motor impairments caused by Quinolinic Acid (QA) in rats. QA treatment affected cognitive function, as demonstrated by the Novel object recognition and the Morris water maze tests, and caused substantial disturbances in motor activity, as demonstrated by rotarod and footprint analyses. QA-treated rats also exhibited higher oxidative and nitrosative stress, lower Glutathione (GSH) levels, higher nitrite and lipid peroxidation, cholinergic dysfunction, and abnormalities in mitochondrial complexes I, II, and IV in the striatum and hippocampus regions. Cranberry (2 g/kg p.o.) significantly enhanced memory, learning, and motor coordination. Cranberry supplementation enhanced GSH levels, decreased MDA concentration, and improved mitochondrial function and cholinergic activity. According to a histological study, cranberries can protect against neuronal degeneration and inflammation. 

CONCLUSION: These findings indicate that cranberries may have neuroprotective properties, presumably through antioxidant, anti-inflammatory, and anti-excitotoxic processes that promote brain plasticity, neurogenesis, and neurotransmitter systems. This establishes the potential of cranberries as a prospective natural treatment for cognitive deficits and neurodegenerative illnesses, suggesting the need for additional research to understand the underlying mechanisms and human application better.

Rich in polyphenols, cranberry juice (CJ) with high antioxidant activity is believed to contribute to various health benefits. However, our knowledge of the neuroprotective potential of cranberries is limited. Previously, we have demonstrated that CJ treatment controls oxidative stress in several organs, with the most evident effect in the brain. In this study, we examined the capability of CJ for protection against Parkinson’s disease (PD) in a rotenone (ROT) rat model. Wistar rats were administered with CJ in a dose of 500 mg/kg b.w./day (i.g.) and subcutaneously injected with ROT (1.3 mg/kg b.w./day). The experiment lasted 45 days, including 10 days pre-treatment with CJ and 35 days combined treatment with CJ and ROT. We quantified the expression of α-synuclein and apoptosis markers in the midbrain, performed microscopic examination, and assessed postural instability to evaluate the CJ neuroprotective effect. Our results indicate that the juice treatment provided neuroprotection, as evidenced by declined α-synuclein accumulation, Bax and cleaved/active caspase-9 expression, and normalized cytochrome c level that was accompanied by the enhancement of neuronal activity survival and improved postural instability. Importantly, we also found that long-term administration of CJ alone in a relatively high dose may exert a deleterious effect on cell survival in the midbrain.