Antiepileptic and Neuroprotective Effects of Rheum tanguticum Root Extract on Trimethyltin-Induced Epilepsy and Neurodegeneration: In Vivo and in Silico Analyses.

Autor:	Choi JY; Namdaemun Sehwa Korean Medical Clinic, 04529 Seoul, Republic of Korea., Kang S; Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea., Tran MN; Korean Medicine Data Division, Korea Institute of Oriental Medicine, 34054 Daejeon, Republic of Korea.; Korean Convergence Medical Science, University of Science and Technology, 34113 Daejeon, Republic of Korea.; Faculty of Traditional Medicine, Hue University of Medicine and Pharmacy, Hue University, 49000 Thua Thien Hue, Vietnam., Lee S; Korean Medicine Data Division, Korea Institute of Oriental Medicine, 34054 Daejeon, Republic of Korea.; Korean Convergence Medical Science, University of Science and Technology, 34113 Daejeon, Republic of Korea., Ryu SM; Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 58245 Naju-si, Jeollanam-do, Republic of Korea., Chae SW; Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 58245 Naju-si, Jeollanam-do, Republic of Korea.; Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, 56212 Jeongeup, Jeollabuk-do, Republic of Korea., Kim DH; Department of Oriental Medicine, College of Oriental Medicine, Dongshin University, 58245 Naju-si, Jeollanam-do, Republic of Korea., Lee YE; Department of Oriental Medicine, College of Oriental Medicine, Dongshin University, 58245 Naju-si, Jeollanam-do, Republic of Korea., Jeong S; Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea., Moon C; Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea., Kim JS; Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea., Lee SI; Department of Oriental Medicine, College of Oriental Medicine, Dongshin University, 58245 Naju-si, Jeollanam-do, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Journal of integrative neuroscience [J Integr Neurosci] 2024 Jun 21; Vol. 23 (6), pp. 122.
DOI:	10.31083/j.jin2306122
Abstrakt:	Background: Rheum tanguticum root, cataloged as " Daehwang " in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. Methods: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. Results: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor ( TNF-α ), glial fibrillary acidic protein ( GFAP ), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration ( p = 4.35 × 10-5) and TNF signaling pathway ( p = 9.94 × 10-5). Conclusions: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications. Competing Interests: The authors declare no conflict of interest. Changjong Moon is serving as one of the Editorial Board members/Guest editors of this journal. We declare that Changjong Moon had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jesús Pastor and Gernot Riedel. (© 2024 The Author(s). Published by IMR Press.)
Databáze:	MEDLINE
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