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4(α-L-鼠李糖氧基)-苄基异硫氰酸酯,一种生物活性植物化学物质,可减轻脊髓损伤实验模型中的继发性损伤。

4(α-l-rhamnosyloxy)-benzyl isothiocyanate, a bioactive phytochemical that attenuates secondary damage in an experimental model of spinal cord injury.

作者信息

Giacoppo Sabrina, Galuppo Maria, De Nicola Gina Rosalinda, Iori Renato, Bramanti Placido, Mazzon Emanuela

机构信息

IRCCS Centro Neurolesi 'Bonino-Pulejo', Via Provinciale Palermo, contrada Casazza, 98124 Messina, Italy.

Consiglio per la Ricerca e la sperimentazione in Agricoltura, Centro di Ricerca per le Colture Industriali (CRA-CIN), Via di Corticella 133, 40128 Bologna, Italy.

出版信息

Bioorg Med Chem. 2015 Jan 1;23(1):80-8. doi: 10.1016/j.bmc.2014.11.022. Epub 2014 Nov 22.

DOI:10.1016/j.bmc.2014.11.022
PMID:25497964
Abstract

4(α-l-Rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) is released from the precursor 4(α-l-rhamnosyloxy)-benzyl glucosinolate (glucomoringin; GMG) by myrosinase (β-thioglucoside glucohydrolase; E.C. 3.2.1.147) catalyzed hydrolysis. GMG is an uncommon member of the glucosinolate group as it presents a unique characteristic consisting in a second glycosidic residue within the side chain. It is a typical glucosinolate found in large amounts in the seeds of Moringa oleifera Lam., the most widely distributed plant of the Moringaceae family. GMG was purified from seed-cake of M. oleifera and was hydrolyzed by myrosinase at neutral pH in order to form the corresponding GMG-ITC. This bioactive phytochemical can play a key role in counteracting the inflammatory response connected to the oxidative-related mechanisms as well as in the control of the neuronal cell death process, preserving spinal cord tissues after injury in mice. Spinal cord trauma was induced in mice by the application of vascular clips (force of 24g) for 1 min., via four-level T5-T8 after laminectomy. In particular, the purpose of this study was to investigate the dynamic changes occurring in the spinal cord after ip treatment with bioactive GMG-ITC produced 15 min before use from myrosinase-catalyzed hydrolysis of GMG (10mg/kg body weight+5 μl Myr mouse/day). The following parameters, such as histological damage, distribution of reticular fibers in connective tissue, nuclear factor (NF)-κB translocation and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) degradation, expression of inducible Nitric Oxide Synthases (iNOS), as well as apoptosis, were evaluated. In conclusion, our results show a protective effect of bioactive GMG-ITC on the secondary damage, following spinal cord injury, through an antioxidant mechanism of neuroprotection. Therefore, the bioactive phytochemical GMG-ITC freshly produced before use by myrosinase-catalyzed hydrolysis of pure GMG, could prove to be useful in the treatment of spinal cord trauma.

摘要

4(α-L-鼠李糖氧基)-苄基异硫氰酸酯(葡糖辣木素异硫氰酸酯;GMG-ITC)由黑芥子酶(β-硫代葡萄糖苷葡萄糖水解酶;E.C. 3.2.1.147)催化水解,从其前体4(α-L-鼠李糖氧基)-苄基硫代葡萄糖苷(葡糖辣木素;GMG)释放而来。GMG是硫代葡萄糖苷基团中一个不常见的成员,因为它具有一个独特的特征,即在侧链内含有第二个糖苷残基。它是一种典型的硫代葡萄糖苷,大量存在于辣木科分布最广的植物辣木(Moringa oleifera Lam.)的种子中。GMG从辣木种子饼中纯化出来,并在中性pH条件下被黑芥子酶水解,以形成相应的GMG-ITC。这种生物活性植物化学物质在对抗与氧化相关机制有关的炎症反应以及控制神经元细胞死亡过程中可能发挥关键作用,在小鼠脊髓损伤后保护脊髓组织。通过在椎板切除术后经四级T5-T8施加血管夹(24g力)1分钟,诱导小鼠脊髓损伤。具体而言,本研究的目的是调查腹腔注射在使用前15分钟由黑芥子酶催化水解GMG产生的生物活性GMG-ITC(10mg/kg体重 + 5μl黑芥子酶/小鼠/天)后脊髓中发生的动态变化。评估了以下参数,如组织学损伤、结缔组织中网状纤维的分布、核因子(NF)-κB易位、B细胞抑制剂κ轻链多肽基因增强子的核因子α(IκB-α)降解、诱导型一氧化氮合酶(iNOS)的表达以及细胞凋亡。总之,我们的结果表明生物活性GMG-ITC通过神经保护的抗氧化机制对脊髓损伤后的继发性损伤具有保护作用。因此,在使用前由黑芥子酶催化水解纯GMG新鲜产生的生物活性植物化学物质GMG-ITC可能被证明对治疗脊髓创伤有用。

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