Mairuae Nootchanat, Noisa Parinya, Palachai Nut
Biomedical Research Unit, Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand.
School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
Molecules. 2024 Dec 22;29(24):6046. doi: 10.3390/molecules29246046.
The rising prevalence of neurodegenerative disorders underscores the urgent need for effective interventions to prevent neuronal cell death. This study evaluates the neuroprotective potential of phytosome-encapsulated 6-gingerol- and 6-shogaol-enriched extracts from Roscoe (6GS), bioactive compounds renowned for their antioxidant and anti-inflammatory properties. The novel phytosome encapsulation technology employed enhances the bioavailability and stability of these compounds, offering superior therapeutic potential compared to conventional formulations. Additionally, the study investigates the role of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-signaling pathway, a key mediator of the neuroprotective effects of 6GS. Neurotoxicity was induced in SH-SY5Y cells (a human neuroblastoma cell line) using 200 μM of hydrogen peroxide (HO), following pretreatment with 6GS at concentrations of 15.625 and 31.25 μg/mL. Cell viability was assessed via the MTT assay alongside evaluations of reactive oxygen species (ROS), antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]), oxidative stress markers (malondialdehyde [MDA]), and molecular mechanisms involving the PI3K/Akt pathway, apoptotic factors (B-cell lymphoma-2 [Bcl-2] and caspase-3), and inflammatory markers (tumor necrosis factor-alpha [TNF-α]). The results demonstrated that 6GS significantly improved cell viability, reduced ROS, MDA, TNF-α, and caspase-3 levels, and enhanced antioxidant enzyme activities. Furthermore, 6GS treatment upregulated PI3K, Akt, and Bcl-2 expression while suppressing caspase-3 activation. Activation of the PI3K/Akt pathway by 6GS led to phosphorylated Akt-mediated upregulation of Bcl-2, promoting neuronal survival and attenuating oxidative stress and inflammation. Moreover, Bcl-2 inhibited ROS generation, further mitigating neurotoxicity. These findings suggest that phytosome encapsulation enhances the bioavailability of 6GS, which through activation of the PI3K/Akt pathway, exhibits significant neuroprotective properties. Incorporating these compounds into functional foods or dietary supplements could offer a promising strategy for addressing oxidative stress and neuroinflammation associated with neurodegenerative diseases.
神经退行性疾病患病率的上升凸显了采取有效干预措施预防神经元细胞死亡的迫切需求。本研究评估了植物脂质体包裹的、富含6-姜酚和6-姜烯酚的罗斯科提取物（6GS）的神经保护潜力，这些生物活性化合物以其抗氧化和抗炎特性而闻名。所采用的新型植物脂质体包封技术提高了这些化合物的生物利用度和稳定性，与传统制剂相比具有更高的治疗潜力。此外，该研究还调查了磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路的作用，这是6GS神经保护作用的关键介质。在用浓度为15.625和31.25μg/mL的6GS预处理后，使用200μM过氧化氢（HO）在SH-SY5Y细胞（一种人神经母细胞瘤细胞系）中诱导神经毒性。通过MTT法评估细胞活力，同时评估活性氧（ROS）、抗氧化酶活性（超氧化物歧化酶[SOD]、过氧化氢酶[CAT]、谷胱甘肽过氧化物酶[GSH-Px]）、氧化应激标志物（丙二醛[MDA]）以及涉及PI3K/Akt途径、凋亡因子（B细胞淋巴瘤-2[Bcl-2]和半胱天冬酶-3）和炎症标志物（肿瘤坏死因子-α[TNF-α]）的分子机制。结果表明，6GS显著提高了细胞活力，降低了ROS、MDA、TNF-α和半胱天冬酶-3水平，并增强了抗氧化酶活性。此外，6GS处理上调了PI3K、Akt和Bcl-2的表达，同时抑制了半胱天冬酶-3的激活。6GS对PI3K/Akt途径的激活导致磷酸化Akt介导的Bcl-2上调，促进神经元存活并减轻氧化应激和炎症。此外，Bcl-2抑制ROS的产生，进一步减轻神经毒性。这些发现表明，植物脂质体包封提高了6GS的生物利用度，6GS通过激活PI3K/Akt途径表现出显著的神经保护特性。将这些化合物纳入功能性食品或膳食补充剂可能为解决与神经退行性疾病相关的氧化应激和神经炎症提供一种有前景的策略。
