State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, PR China; Natural Products Research Center of Guizhou Province, Guiyang 550014, PR China.
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Phytomedicine. 2024 Oct;133:155893. doi: 10.1016/j.phymed.2024.155893. Epub 2024 Jul 26.
Depression is a serious and complex mental disease that has attracted worldwide attention because of its high incidence rate, high disability rate and high mortality. Excitotoxicity is one of the most important mechanisms involved in the pathophysiological process of depression. In our previous studies, n-butanol extract from maize roots was found to have good neuroprotective effects due to its antioxidative activity. However, the antidepressive effective constituents, efficacy in vivo and mechanism of action of maize root extracts have not been determined.
This study aimed to determine the main active neuroprotective compound in maize root extract and investigate its antidepressant effects and possible underlying mechanism in vitro and in vivo.
Sixteen extracts were isolated and purified from maize roots. The active components of the most active extracts of maize roots (hereafter referred to as EM 2) were identified using UF-HPLC-QTOF/MS. In vitro cell models of NMDA-induced excitotoxicity in SH-SY5Y cells were used to analyze the anti-excitatory activity of the extracts. The MTT assay and Annexin V-FITC/PI Apoptosis Detection were used to evaluate cell viability. Several network pharmacological strategies have been employed to investigate the potential mechanism of action of EM 2. The effects of EM 2 on depressive-like behaviors were evaluated in CUMS mice. Changes in the levels of related proteins were detected via western blotting.
Among the 16 extracts extracted by n-butanol, EM 2 was determined to be the most active extract against NMDA-induced excitotoxicity by n-butanol extraction. Meanwhile, seventeen compounds were further identified as the main active components of EM 2. Mechanistically, EM 2 inhibited NMDA-induced excitatory injury in SH-SY5Y cells and alleviated the depressive-like behaviors of CUMS mice by suppressing NR2B and subsequently mediating the downstream CREB/TRKB/BDNF, PI3K/Akt and MAPK pathways, as well as the Nrf2/HO-1 antioxidant signaling pathway.
The study indicated that EM 2 could potentially be developed as a potential therapeutic candidate to cure depression in NMDA-induced excitatory damage.
抑郁症是一种严重且复杂的精神疾病，由于其高发病率、高致残率和高死亡率而引起了全球关注。兴奋性毒性是抑郁症病理生理过程中最重要的机制之一。在我们之前的研究中，发现玉米根的正丁醇提取物由于其抗氧化活性而具有良好的神经保护作用。然而，玉米根提取物的抗抑郁有效成分、体内疗效和作用机制尚未确定。
本研究旨在确定玉米根提取物中的主要活性神经保护化合物，并在体外和体内研究其抗抑郁作用及其可能的作用机制。
从玉米根中分离和纯化了 16 种提取物。使用 UF-HPLC-QTOF/MS 鉴定玉米根最活跃提取物（以下简称 EM 2）的活性成分。在 SH-SY5Y 细胞中使用 NMDA 诱导的兴奋性毒性体外细胞模型分析提取物的抗兴奋性作用。MTT 测定和 Annexin V-FITC/PI 凋亡检测用于评估细胞活力。采用几种网络药理学策略研究 EM 2 的潜在作用机制。在 CUMS 小鼠中评估 EM 2 对抑郁样行为的影响。通过 Western blot 检测相关蛋白水平的变化。
在正丁醇提取的 16 种提取物中，通过正丁醇提取，确定 EM 2 是对抗 NMDA 诱导兴奋性毒性最活跃的提取物。同时，进一步鉴定出 17 种化合物为 EM 2 的主要活性成分。在机制上，EM 2 通过抑制 NMDA 诱导的 SH-SY5Y 细胞兴奋损伤，并通过抑制 NR2B 及其下游 CREB/TRKB/BDNF、PI3K/Akt 和 MAPK 通路以及 Nrf2/HO-1 抗氧化信号通路，缓解 CUMS 小鼠的抑郁样行为。
该研究表明，EM 2 可能成为治疗 NMDA 诱导兴奋性损伤的潜在候选药物。
