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.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
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.

通过调节alcl3诱导的大鼠记忆损伤中的tau和β-分泌酶通路,揭示香豆乙醇提取物的神经保护潜力及其植物化学特征。
阿尔茨海默病(AD)是一种广泛存在的疾病,严重影响成年人和社区。除高龄和遗传易感性外,病因尚不清楚。天然产物由于其有效性、安全性和可及性,为AD的治疗提供了有利的优势。本研究以多奈哌齐为对照药,研究了化学表征的Ipomoea carnea乙醇提取物(IPC-EtOH)在行为学、生化、组织学和分子水平上对AlCl3暴露引起的大鼠认知损伤的促进作用。进行行为学测试(自发交替t迷宫和开放场试验)、GSK3β、CREB、FOXO1a、β-分泌酶、tau、氧化应激生物标志物、组织病理学和环氧化酶2 (COX-2)免疫组织化学检测。利用UPLC-ESI-qTOF-MS结合分子网络对IPC-EtOH进行化学分析,鉴定出83种生物活性代谢物,包括pyrrolizidine生物碱和肉桂酸衍生物,这些都是之前从该物种中描述过的。与对照组相比,注射AlCl3显著提高tau、β-分泌酶、GSSG、GSK-3β和FOXO3a水平,下调CAT、SOD和CREB,皮质和海马中COX-2免疫表达较强。口服多奈哌齐或IPC-EtOH对alcl3治疗的大鼠恢复了这些脑区接近正常的功能,显著减轻了空间学习、记忆和运动障碍。这些结果表明,IPC-EtOH可能是一种很有前景的治疗铝诱导的神经毒性的方法,尽管需要进一步的研究来阐明其确切的作用机制。这些结果强调了鸢尾草乙醇提取物作为一种有吸引力的治疗阿尔茨海默病的潜力,通过展示其对alcl3诱导的记忆损伤的大鼠的神经保护和记忆增强特性。
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来源期刊
Inflammopharmacology
Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY
CiteScore
8.00
自引率
3.40%
发文量
200
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 [...]
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