Muke Suraj, Kaikini Aakruti, Peshattiwar Vaibhavi, Bagle Sneha, Dighe Vikas, Sathaye Sadhana
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.
Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health, Mumbai, India.
Front Pharmacol. 2018 Sep 3;9:992. doi: 10.3389/fphar.2018.00992. eCollection 2018.
Epilepsy is a brain disorder characterized by sudden recurrent seizures. Considering the fact that epileptogenesis is a process that affects the quality of life, our goal is to delay the process of epileptogenesis and to increase the latency of epileptic attacks, offering better quality of life to patients. Traditional system of medicines has a promise in some of the medicines, which have been used for the treatment of epilepsy. One such medicinal plant is (EA). According to Ayurvedic philosophy, the juice of leaves of EA is pounded with garlic and pepper for the treatment of epilepsy. Taking clue from the Ayurvedic system of medicines, we formulated coumarin fraction of EA, namely, coumarin nasal formulation (CNF) for its nasal delivery. CNF was analyzed by using high performance liquid chromatography (HPLC) and ultraviolet absorption spectroscopy for its drug content determination. drug release studies were performed in simulated nasal electrolyte solution (SNES) maintaining constant pH of 5.5 at 37°C. Irritation by CNF was evaluated using hen's egg test chorioallantoic membrane (HET-CAM) assay. Formulation was found to be non-irritant in HET-CAM assay. CNF was further assessed by measuring the progress and attainment of pentylenetetrazole (PTZ) kindling in mice. Neuronal changes were assessed by hematoxylin and eosin (H&E) and Nissl staining technique. Glial fibrillary acidic protein (GFAP) a neuroinflammatory marker and tumor necrosis factor alpha (TNF-α) an inflammatory marker were also measured. CNF (10 mg/kg, nasal route) when given as a pretreatment lowered seizure score and delayed the progression of seizure similar to diazepam. CNF decreased the PTZ induced oxidative damage, TNF-α as well as GFAP levels in the midbrain tissue particularly in hippocampus region. The results suggest that CNF may be a promising therapeutic approach to offer protection from sudden recurrent seizures alone or in combination with current drugs in management of epilepsy.
癫痫是一种以突然反复发作性癫痫发作为特征的脑部疾病。鉴于癫痫发生是一个影响生活质量的过程，我们的目标是延缓癫痫发生过程并延长癫痫发作的潜伏期，从而为患者提供更好的生活质量。传统医学体系中的一些药物在癫痫治疗方面具有前景，一种这样的药用植物是（EA）。根据阿育吠陀医学理念，EA叶片的汁液与大蒜和胡椒一起捣碎用于治疗癫痫。借鉴阿育吠陀医学体系，我们制备了EA的香豆素部分，即用于鼻腔给药的香豆素鼻腔制剂（CNF）。使用高效液相色谱法（HPLC）和紫外吸收光谱法对CNF进行药物含量测定分析。在37°C下维持恒定pH值为5.5的模拟鼻电解质溶液（SNES）中进行药物释放研究。使用鸡胚绒毛尿囊膜（HET - CAM）试验评估CNF的刺激性。在HET - CAM试验中发现该制剂无刺激性。通过测量小鼠戊四氮（PTZ）点燃的进程和程度进一步评估CNF。通过苏木精和伊红（H&E）染色及尼氏染色技术评估神经元变化。还测量了神经炎症标志物胶质纤维酸性蛋白（GFAP）和炎症标志物肿瘤坏死因子α（TNF -α）。作为预处理给予的CNF（10mg/kg，鼻腔途径）降低了癫痫发作评分并延缓了癫痫发作进程，类似于地西泮。CNF降低了PTZ诱导的中脑组织特别是海马区的氧化损伤、TNF -α以及GFAP水平。结果表明，CNF可能是一种有前景的治疗方法，可单独或与当前药物联合用于癫痫管理，以预防突然反复发作性癫痫发作。
