肉豆蔻提取物对锂-匹罗卡品诱导的大鼠自发性反复癫痫发作及相关心律失常的保护作用。

Protective effect of Nardostachys jatamansi extract against lithium-pilocarpine-induced spontaneous recurrent seizures and associated cardiac irregularities in a rat model.

机构信息

Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, 176061, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

J Ethnopharmacol. 2023 May 23;308:116280. doi: 10.1016/j.jep.2023.116280. Epub 2023 Feb 20.

DOI:10.1016/j.jep.2023.116280

PMID:36813245

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Nardostachys jatamansi (D.Don) DC. is a perennial herbaceous medicinal plant widely used for the ethnomedical treatment of various ailments. The underground parts of the plants are used in traditional medicine to manage epilepsy and other cardiovascular conditions.

AIM OF THE STUDY

The present study was undertaken to investigate the efficacy of a characterized hydroalcoholic extract (NJET) of Nardostachys jatamansi in the lithium-pilocarpine rat model of spontaneous recurrent seizures (SRS) and associated cardiac irregularities.

MATERIALS AND METHODS

NJET was prepared by percolation using 80% ethanol. The dried NEJT was subjected to UHPLC-qTOF-MS/MS for chemical characterization. Molecular docking studies were performed using the characterized compounds to understand mTOR interactions. The animals showing SRS following lithium-pilocarpine administration were treated with NJET for 6 weeks. Afterward, seizure severity, cardiac parameters, serum biochemistry, and histopathological parameters were studied. The cardiac tissue was processed for specific protein and gene expression studies.

RESULTS

The UHPLC-qTOF-MS/MS characterized 13 compounds in NJET. The identified compounds subjected to molecular docking showed promising binding affinities toward mTOR. There was a dose-dependent decrease in the severity of SRS following the extract administration. A reduction in mean arterial pressure and serum biochemical markers (lactate dehydrogenase and creatine kinase) was also observed following NJET treatment in epileptic animals. Histopathological investigations revealed reduced degenerative changes and decreased fibrosis following the extract treatment. The cardiac mRNA level of Mtor, Rps6, Hif1a, and Tgfb3 was reduced in the extract-treated groups. Further, a similar reduction in the protein expression of p-mTOR and HIF-1α was also observed following NJET treatment in the cardiac tissue.

CONCLUSIONS

The results concluded that NJET treatment reduces lithium-pilocarpine-induced recurrent seizures and associated cardiac irregularities via downregulation of the mTOR signalling pathway.

摘要

民族药理学相关性

甘松香（D.Don）DC. 是一种多年生草本药用植物，广泛用于治疗各种疾病的民族医学。植物的地下部分用于传统医学，以治疗癫痫和其他心血管疾病。

研究目的

本研究旨在研究甘松香（Nardostachys jatamansi）的一种特征性水醇提取物（NJET）在锂匹鲁卡品大鼠自发性复发性癫痫发作（SRS）模型中的疗效及其相关的心脏异常。

材料和方法

NJET 通过 80%乙醇渗漉法制备。干燥的 NEJT 进行 UHPLC-qTOF-MS/MS 化学特征分析。使用特征化合物进行分子对接研究，以了解 mTOR 相互作用。在给予锂匹鲁卡品后出现 SRS 的动物用 NJET 治疗 6 周。之后，研究了癫痫发作严重程度、心脏参数、血清生化和组织病理学参数。对心脏组织进行特定蛋白和基因表达研究。

结果

UHPLC-qTOF-MS/MS 鉴定出 NJET 中的 13 种化合物。经分子对接鉴定的化合物对 mTOR 表现出良好的结合亲和力。在提取物给药后，SRS 的严重程度呈剂量依赖性下降。在癫痫动物中，NJET 治疗还观察到平均动脉压和血清生化标志物（乳酸脱氢酶和肌酸激酶）降低。组织病理学研究表明，在提取物治疗后，退行性变化和纤维化减少。在提取物治疗组中，心脏组织中 Mtor、Rps6、Hif1a 和 Tgfb3 的 mRNA 水平降低。此外，在心脏组织中，NJET 治疗后也观察到 p-mTOR 和 HIF-1α 的蛋白表达类似减少。