Unveiling the neuroprotective potential of Ipomoea carnea ethanol extract via the modulation of tau and β-secretase pathways in AlCl3-induced memory impairment in rats in relation to its phytochemical profiling.
Walaa A El-Kashak, Ahmed F Essa, Mohamed F Abdelhameed, Yasmine H Ahmed, Asmaa S Abd Elkarim, Mai M Elghonemy, Bassant M M Ibrahim, Ahmed H Gaara, Tahia K Mohamed, Abdelsamed I Elshamy
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引用次数: 0
Abstract
Alzheimer's disease (AD) is a widespread condition that affects adults and the community considerably. The causes are yet unknown, except from advanced age and genetic predisposition. Natural products provided advantageous advantages for managing AD due to their efficacy, safety, and accessibility. The memory boosting effects of chemically characterized Ipomoea carnea ethanol extract (IPC-EtOH) on behavioral, biochemical, histological, and molecular levels against cognitive impairment induced by AlCl3 exposure in rats were assessed using donepezil as a reference drug. Behavioral tests (spontaneous alternation T-maze and open field test) and assays for GSK3β, CREB, FOXO1a, β-secretase, tau, oxidative stress biomarkers, histopathology, and immunohistochemistry for cyclooxygenase 2 (COX-2) were conducted. The chemical profiling of IPC-EtOH using UPLC-ESI-qTOF-MS coupled with molecular networking revealed the identification of 83 bioactive metabolites, including pyrrolizidine alkaloids and cinnamic acid derivatives which previously undescribed from this species. AlCl3 injection significantly elevated tau, β-secretase, GSSG, GSK-3β, and FOXO3a levels and down regulated CAT, SOD, and CREB, with strong COX-2 immunoexpression in the cortex and hippocampus compared to controls. Oral co-administration of donepezil or IPC-EtOH to AlCl3-treated rats restored near-normal function in these brain regions, significantly attenuating spatial learning, memory, and locomotor impairments. These results suggest that IPC-EtOH could be a promising therapy for mitigating aluminum-induced neurotoxicity, though further studies are needed to elucidate its precise mechanisms of action. These outcomes emphasize I. carnea ethanol extract's potential as an appealing therapy for AD by demonstrating its neuroprotective and memory-enhancing properties in rats having AlCl3-induced memory impairment.
期刊介绍:
Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas:
-Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states
-Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs
-Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents
-Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain
-Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs
-Muscle-immune interactions during inflammation [...]