Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer's disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid ß42 (Aß42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3ß/GSK3ß, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aß42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aß42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.

Reversal Effects of Royal Jelly and Propolis Against Cadmium-Induced Hepatorenal Toxicity in Rats.

Heavy metal toxicity is an exponentially growing health problem. In this study, we aimed to assess the protective properties of propolis and royal jelly against cadmium adverse effects. Thirty-two adult male rats were included in our study; kidney and liver functions, histopathological changes, and the level of oxidative stress were evaluated in rats exposed to a daily dose of 4.5 mg cadmium per kilogram of body weight for 1 month and those cotreated simultaneously with either propolis (50 mg/kg/day) or royal jelly (200 mg/kg/day) with cadmium compared to control animals. Cadmium-mediated hepatorenal toxicity was manifested as per the increased oxidative stress, function deterioration, and characteristic histopathological aberrations. The supplementation of royal jelly or propolis restores most of the affected parameters to a level similar to the control group. However, the parameters describing the grade of DNA damage and the interleukin-1ß expression in the liver, as well as the levels of malondialdehyde and metallothionein, were slightly elevated compared to controls, despite the regular use of royal jelly or propolis. It is worth noting that better results were found in the case of royal jelly compared to propolis administration. Most likely, the ability of both products to chelate cadmium and contribute in reducing oxidative stress is of great importance. However, further investigations are needed to complement the knowledge about the expected nutritional and medicinal values.

Cerium oxide nanoparticles could ameliorate behavioral and neurochemical impairments in 6-hydroxydopamine induced Parkinson's disease in rats.

BACKGROUND: Cerium oxide nanoparticles (CeO2NPs) showed promising effects in neurodegenerative diseases including some animal models of Parkinsonism. However, the implication of CeO2NPs in 6-hydroxydopamine (6-OHDA) induced Parkinsonism remains to be investigated. AIM: This study was designed to assess whether CeO2NPs treatment could alleviate neurobehavioral and neurobiochemical deficits in 6-OHDA induced neurotoxicity in rats. MATERIAL AND METHODS: 50 rats received left intrastriatal (IS) injection of either saline (control, n = 10) or 6-OHDA (n = 40). At the third week post-lesion, motor dysfunction was verified using neurobehavioral tests. Then diseased rats received intraperitoneal injection of 0.1, 0.5 or 1 mg/kg of CeO2NPs or vehicle (10 rats each) for 3 weeks. Rats were subjected to behavioral assessments and then sacrificed for biochemical analyses of the striatum. Striatal dopamine levels, oxidative stress markers including total antioxidant capacity (TAC) and malondialdehyde (MDA), and caspase 3 activity as an apoptotic marker were assessed. RESULTS: Different doses of CeO2NPs variably improved motor dysfunctions induced by 6-OHDA injection in open field, Rota Rod and stepping tests. In addition, the neurobiochemical derangements were almost reversed by the 0.5 mg/kg dose of CeO2NPs, while 0.1 mg/kg dose was not sufficient to alter biochemical measurements in the striatum. Administration of 1 mg/kg of CeO2NPs partially ameliorated striatal dopamine and decreased apoptosis without significant effect on oxidative stress. CONCLUSION: The present study showed a putative therapeutic role of CeO2NPs in the treatment of 6-OHDA-induced Parkinsonian rats, and suggested their antioxidant and antiapoptotic effects as possible mechanisms for elevated striatal dopamine level and improved motor performance.