Neurotherapeutic effects of quercetin-loaded nanoparticles and Biochanin-A extracted from Trifolium alexandrinum on PI3K/Akt/GSK-3β signaling in the cerebral cortex of male diabetic rats.
Al-Sayeda Al-Sayed NewairyFatma Ahmad HamaadMayssaa Moharm WahbyMamdooh H GhoneumHeba Mohamed AbdouPublished in: PloS one (2024)
Diabetes mellitus (DM) is a severe metabolic disease that can have significant consequences for cognitive health. Bioflavonoids such as Trifolium alexandrinum (TA), quercetin (Q), and Biochanin-A (BCA) are known to exert a wide range of pharmacological functions including antihyperglycemic activity. This study aimed to investigate the neurotherapeutic effects of quercetin-loaded nanoparticles (Q-LNP) and BCA extracted from TA against diabetes-induced cerebral cortical damage through modulation of PI3K/Akt/GSK-3β and AMPK signaling pathways. Adult male Wistar albino rats (N = 25) were randomly assigned to one of five groups: control, diabetics fed a high-fat diet (HFD) for 2 weeks and intraperitoneally (i.p.) injected with STZ (40 mg/kg), and diabetics treated with Q-LNP (50 mg/kg BW/day), BCA (10 mg/kg BW/day), or TA extract (200 mg/kg BW/day). Treatments were applied by oral gavage once daily for 35 days. Diabetic rats treated with Q-LNP, BCA, and TA extract showed improvement in cognitive performance, cortical oxidative metabolism, antioxidant parameters, and levels of glucose, insulin, triglyceride, and total cholesterol. In addition, these treatments improved neurochemical levels, including acetylcholine, dopamine, and serotonin levels as well acetylcholinesterase and monoamine oxidase activities. Furthermore, these treatments lowered proinflammatory cytokine production for TNF-α and NF-κB; downregulated the levels of IL-1β, iNOS, APP, and PPAR-γ; and attenuated the expressions of PSEN2, BACE, IR, PI3K, FOXO 1, AKT, AMPK, GSK-3β, and GFAP. The histopathological examinations of the cerebral cortical tissues confirmed the biochemical results. Overall, the present findings suggest the potential therapeutic effects of TA bioflavonoids in modulating diabetes-induced cerebral cortical damage.
Keyphrases
- diabetic rats
- pi k akt
- oxidative stress
- signaling pathway
- high fat diet
- glycemic control
- cell proliferation
- type diabetes
- cell cycle arrest
- subarachnoid hemorrhage
- induced apoptosis
- insulin resistance
- epithelial mesenchymal transition
- adipose tissue
- drug delivery
- rheumatoid arthritis
- cardiovascular disease
- blood glucose
- physical activity
- cancer therapy
- mental health
- cerebral ischemia
- brain injury
- skeletal muscle
- uric acid
- immune response
- gene expression
- high glucose
- inflammatory response
- early onset
- endothelial cells
- social media
- nitric oxide synthase
- endoplasmic reticulum stress
- blood brain barrier
- nitric oxide