Al Omairi Naif E, Albrakati Ashraf, Alsharif Khalaf F, Almalki Abdulraheem S, Alsanie Walaa, Abd Elmageed Zakaria Y, Zaafar Dalia, Lokman Maha S, Bauomy Amira A, Belal Saied K, Abdel-Daim Mohamed M, Abdel Moneim Ahmed E, Alyami Hussain, Kassab Rami B
Department of Internal Medicine, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Biology (Basel). 2022 Feb 23;11(3):354. doi: 10.3390/biology11030354.
Prodigiosin (PDG) is a red pigment synthesized by bacterial species with important pharmaceutical and biological activities. Here, we investigated the neuroprotective and anticonvulsant activities of green biosynthesized selenium formulations with PDG (SeNPs-PDG) versus pentylenetetrazole (PTZ)-induced epileptic seizures.
Rats were assigned into six experimental groups: control; PTZ (60 mg/kg, epileptic model); sodium valproate (200 mg/kg) + PTZ; PDG (300 mg/kg) + PTZ; sodium selenite (0.5 mg/kg) + PTZ; and SeNPs-PDG (0.5 mg/kg) + PTZ. The treatment duration is extended to 28 days.
SeNPs-PDG pre-treatment delayed seizures onset and reduced duration upon PTZ injection. Additionally, SeNPs-PDG enhanced the antioxidant capacity of hippocampal tissue by activating the expression of nuclear factor erythroid 2-related factor 2 and innate antioxidants (glutathione and glutathione derivatives, in addition to superoxide dismutase and catalase) and decreasing the levels of pro-oxidants (lipoperoxidation products and nitric oxide). SeNPs-PDG administration inhibited inflammatory reactions associated with epileptic seizure development by suppressing the production and activity of glial fibrillary acidic protein and pro-inflammatory mediators, including interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, SeNPs-PDG protected against hippocampal cell loss following PTZ injection by decreasing the levels of cytosolic cytochrome c, Bax, and caspase-3 and enhancing the expression of anti-apoptotic Bcl-2. Interestingly, SeNPs-PDG restored the PTZ-induced imbalance between excitatory and inhibitory amino acids and improved monoaminergic and cholinergic transmission.
These promising antioxidative, anti-inflammatory, anti-apoptotic, and neuromodulatory activities indicate that SeNPs-PDG might serve as a naturally derived anticonvulsant agent.
灵菌红素（PDG）是一种由细菌合成的红色色素，具有重要的药理和生物学活性。在此，我们研究了绿色生物合成的含PDG的硒制剂（SeNPs-PDG）对戊四氮（PTZ）诱导的癫痫发作的神经保护和抗惊厥活性。
将大鼠分为六个实验组：对照组；PTZ（60mg/kg，癫痫模型）；丙戊酸钠（200mg/kg）+PTZ；PDG（300mg/kg）+PTZ；亚硒酸钠（0.5mg/kg）+PTZ；以及SeNPs-PDG（0.5mg/kg）+PTZ。治疗持续时间延长至28天。
SeNPs-PDG预处理延迟了PTZ注射后的癫痫发作起始并缩短了发作持续时间。此外，SeNPs-PDG通过激活核因子红细胞2相关因子2和天然抗氧化剂（除超氧化物歧化酶和过氧化氢酶外，还有谷胱甘肽和谷胱甘肽衍生物）的表达并降低促氧化剂（脂质过氧化产物和一氧化氮）的水平，增强了海马组织的抗氧化能力。给予SeNPs-PDG通过抑制胶质纤维酸性蛋白和促炎介质（包括白细胞介素-1β、肿瘤坏死因子-α、环氧合酶-2、诱导型一氧化氮合酶和核因子κB）的产生和活性，抑制了与癫痫发作发展相关的炎症反应。此外，SeNPs-PDG通过降低细胞溶质细胞色素c、Bax和半胱天冬酶-3的水平并增强抗凋亡蛋白Bcl-2的表达，保护大鼠免受PTZ注射后海马细胞丢失的影响。有趣的是，SeNPs-PDG恢复了PTZ诱导的兴奋性和抑制性氨基酸之间的失衡，并改善了单胺能和胆碱能传递。
这些有前景的抗氧化、抗炎、抗凋亡和神经调节活性表明，SeNPs-PDG可能作为一种天然来源的抗惊厥药物。
