Martínez María-Aránzazu, Lopez-Torres Bernardo, Maximiliano Jorge-Enrique, Martínez Marta, Martínez-Larrañaga María-Rosa, Ares Irma, Anadón Arturo, Peteiro Cesar, Aymerich Teresa, Casal-Silva Andrea, Cueto Mercedes
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040, Madrid, Spain.
Eur J Pharmacol. 2025 Sep 15;1003:177977. doi: 10.1016/j.ejphar.2025.177977. Epub 2025 Jul 19.
The brown seaweed Bifurcaria bifurcata has gained particular interest in recent years due to its abundance in bioactive linear diterpenes with potential high-value applications. Evidences suggests that oxidative stress is an important mediator of neurodegenerative disorders. In this research study, the aim was to evaluate the potential protective effect of eleganolone, diterpene isolated from the brown seaweed B. bifurcata, on oxidative stressed human neuroblastoma SH-SY5Y cells by tert-butyl hydroperoxide (tert-BOOH). The protective effects of eleganolone on the oxidative stressed SH-SY5Y cells were measured by cell viability, cytotoxicity, oxidative stress biomarkers and antioxidative enzyme activity assays, as well as associated intracellular signaling pathways. The mRNA expression of apoptosis, inflammation, oxidative stress and neuronal development signaling pathway-related genes was analyzed by real-time RT-PCR. Eleganolone prevented the elevation of oxidative stress markers, such as reactive oxygen species, malondialdehyde, nitric oxide and caspase 3/7 activity, as well as induced an increase in reduced glutathione and antioxidant enzyme activities in a dose-dependent manner on oxidative stressed SH-SY5Y cells. Additionally, our data showed that eleganolone downregulated the expression of genes associated with apoptosis (BAX, BNIP3, p53, p38, APAF1), inflammation (NFKB1, TNF-α, IL-6, IL-1β), oxidative stress (HO-1) and neuronal development (CAMK2A, WNT5A, WNT7A) pathways in SH-SY5Y cells exposed to oxidative stressor tert-BOOH. These findings suggest that eleganolone offers neuroprotective potential in ameliorating diverse pathological aspects associated with oxidative stress.
近年来,棕色海藻二叉仙菜因其富含具有潜在高价值应用的生物活性线性二萜而备受关注。有证据表明,氧化应激是神经退行性疾病的重要介导因素。在本研究中,目的是评估从棕色海藻二叉仙菜中分离出的二萜eleganolone对叔丁基过氧化氢(tert-BOOH)诱导的氧化应激人神经母细胞瘤SH-SY5Y细胞的潜在保护作用。通过细胞活力、细胞毒性、氧化应激生物标志物和抗氧化酶活性测定以及相关的细胞内信号通路来测量eleganolone对氧化应激SH-SY5Y细胞的保护作用。通过实时RT-PCR分析凋亡、炎症、氧化应激和神经元发育信号通路相关基因的mRNA表达。Eleganolone可防止氧化应激标志物如活性氧、丙二醛、一氧化氮和半胱天冬酶3/7活性的升高,并以剂量依赖的方式诱导氧化应激的SH-SY5Y细胞中还原型谷胱甘肽和抗氧化酶活性增加。此外,我们的数据表明,eleganolone下调了暴露于氧化应激剂叔丁基过氧化氢的SH-SY5Y细胞中与凋亡(BAX、BNIP3、p53、p38、APAF1)、炎症(NFKB1、TNF-α、IL-6、IL-1β)、氧化应激(HO-1)和神经元发育(CAMK2A、WNT5A、WNT7A)途径相关基因的表达。这些发现表明,eleganolone在改善与氧化应激相关的各种病理方面具有神经保护潜力。