秋葵籽多糖通过调节Nrf2/HO-1、HMGB1/RAGE/TLR4/NF-κB、NLRP3/Caspase-1、JAK-2/STAT-3、AMPK/SIRT1/m-TOR、PI3K/AKT/CREB/BDNF/TrkB和PERK/CHOP/Bcl-2轴减轻神经炎症和认知障碍。
Okra seed polysaccharides mitigate neuroinflammation and cognitive impairment via modulation of Nrf2/HO-1, HMGB1/RAGE/TLR4/NF-κB, NLRP3/Caspase-1, JAK-2/STAT-3, AMPK/SIRT1/m-TOR, PI3K/AKT/CREB/BDNF/TrkB and PERK/CHOP/Bcl-2 axes.
作者信息
Nazeam Jilan A, Black Ian, Mulamoottil Varughese A, Selim Nabil M, El Shiekh Riham A, Abu-Elfotuh Karema, Hamdan Ahmed M E, Gowifel Ayah M H, Hafez Shaimaa M, Mohamed Ehsan K, Atwa Ahmed M, El Hefnawy Hala Mohamed, Azadi Parastoo
机构信息
Department of Pharmacognosy, Faculty of Pharmacy, October 6 University, Giza, Egypt; Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
出版信息
Int Immunopharmacol. 2025 Feb 20;148:114110. doi: 10.1016/j.intimp.2025.114110. Epub 2025 Jan 24.
Global healthcare systems are under tremendous strain due to the increasing prevalence of neurodegenerative disorders. Growing data suggested that overconsumption of high-fat/high-carbohydrates diet (HFHCD) is associated with enhanced incidence of metabolic alterations, neurodegeneration, and cognitive dysfunction. Functional foods have gained prominence in curbing metabolic and neurological deficits. Consequently, this study endeavored to explore effects of purified Okra seed polysaccharides (OP) (Abelmoschus esculentus (L.) Moench) against HFHCD-induced metabolic alterations and cognitive dysfunction, with elucidating underlying contributed mechanistic pathways. OP hydrolysate was analyzed using GC-MS analysis. The biological study encompassed two phases, the first phase I (model establishment phase), for 3 months, involved a control group, fed standard diet, and HFHCD group. The second phase (phase II) where HFHCD fed rats were re-divided into 3 equal subgroups, 1st subgroup received HFHCD, whereas second and third subgroups received OP, 200 or 400 mg/kg/day, respectively, for 28 days. GC-MS characterized OP as an arabinogalactouranan and revealed the monosaccharide composition as galacturonic acid: arabinose: glucose: galactose: rhamnose: xylose in ratio of 28.2: 23.3: 11.5: 4.2: 3.5: 2.0. The findings demonstrated that OP dose-dependently mitigated HFHCD-induced rise in body weights, lipid profiles, levels of blood glucose and disruption in behavioral outcomes, neurotransmitters, together with histopathological alterations in brain. Moreover, OP dose-dependently improved redox, neuroinflammatory, endoplasmic reticulum (ER) stress, autophagic and apoptotic biomarkers. OP can be regarded as promising functional food candidate to hamper HFHCD-induced metabolic alterations and cognitive deficit, via enhancing Nrf2/HO-1, AMPK/SIRT1 and PI3K/AKT/CREB axes, long with dampening of HMGB1/RAGE/TLR4, NLRP3/Caspase-1, JAK-2/STAT-3 and PERK/CHOP axes.
由于神经退行性疾病的患病率不断上升，全球医疗保健系统承受着巨大压力。越来越多的数据表明，高脂肪/高碳水化合物饮食（HFHCD）的过度摄入与代谢改变、神经退行性变和认知功能障碍的发病率增加有关。功能性食品在抑制代谢和神经缺陷方面已受到关注。因此，本研究致力于探索纯化的秋葵种子多糖（OP）（黄秋葵）对HFHCD诱导的代谢改变和认知功能障碍的影响，并阐明其潜在的作用机制途径。使用气相色谱-质谱联用（GC-MS）分析法对OP水解产物进行分析。生物学研究包括两个阶段，第一阶段（模型建立阶段）为期3个月，包括一个喂食标准饮食的对照组和一个HFHCD组。第二阶段（阶段II），将喂食HFHCD的大鼠重新分为3个相等的亚组，第一个亚组继续喂食HFHCD，而第二个和第三个亚组分别接受200或400mg/kg/天的OP，持续28天。GC-MS将OP表征为阿拉伯半乳聚糖，并揭示其单糖组成为半乳糖醛酸：阿拉伯糖：葡萄糖：半乳糖：鼠李糖：木糖，比例为28.2:23.3:11.5:4.2:3.5:2.0。研究结果表明，OP剂量依赖性地减轻了HFHCD诱导的体重增加、血脂水平、血糖水平升高以及行为结果、神经递质的紊乱，以及大脑的组织病理学改变。此外，OP剂量依赖性地改善了氧化还原、神经炎症、内质网（ER）应激、自噬和凋亡生物标志物。OP可被视为一种有前景的功能性食品候选物，通过增强Nrf2/HO-1、AMPK/SIRT1和PI3K/AKT/CREB轴，以及抑制HMGB1/RAGE/TLR4、NLRP3/Caspase-1、JAK-2/STAT-3和PERK/CHOP轴，来减轻HFHCD诱导的代谢改变和认知缺陷。
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