Neuroprotective effect of Geijigadaehwang-tang against trimethyltin-induced hippocampal neurodegeneration: An in vitro and in vivo study. (5th October 2022)

• Record Type: Journal Article
• Authors: Lee, Sueun; Ryu, Seung Mok; Kim, Do-Hyun; Lee, Ye Eun; Lee, Sung-Jun; Kang, Sohi; Kim, Joong Sun; Lee, Soong-In
• Is Part Of: Journal of ethnopharmacology. Volume 296(2022)
• Publication Date: 2022-10-05
• Subjects: Neurodegenerative disorders -- Inflammation -- Alzheimer -- Dementia -- Epilepsy; ASC apoptosis-associated speck-like protein containing a CARD -- cDNA complementary DNA -- CO2 carbon dioxide -- DG dentate gyrus -- DMEM Dulbecco's modified Eagle's medium -- FBS fetal bovine serum -- FJB Fluoro-Jade B -- GDT Geijigadaehwang-tang -- HO1 heme oxygenase 1 -- IL interleukin -- iNOS inducible nitric oxide synthase -- mRNA messenger RNA -- NF nuclear factor -- NLRP3 nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 -- NRF2 nuclear factor erythroid-2-related factor 2 -- qRT-PCR quantitative reverse transcription polymerase chain -- RT room temperature -- SDS sodium dodecyl sulfate -- TNF-α tumor necrosis factor alpha -- TMT trimethyltin -- UPLC ultra-performance liquid chromatography -- vs. versus; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115451
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Patients with dementia are diagnosed with deficiency patterns and interior patterns in traditional Chinese medicine due to decreased physical strength, mental atrophy including cognitive function, and decreased motor function in the gastrointestinal tract. Since "greater yin symptom" in Shanghanlun has been interpreted as interior, deficiency, and cold pattern in traditional Chinese medicine, it is necessary to determine whether Geijigadaehwang-tang (GDT) has therapeutic effects on neurodegenerative diseases and the underlying mechanism if it has such effects. Aims of the study: Trimethyltin (TMT), a neurotoxic organotin compound, has been used to induce several neurodegenerative diseases, including epilepsy and Alzheimer's disease. This study aimed to evaluate the therapeutic efficacy of GDT for TMT-induced hippocampal neurodegeneration and seizures and to determine the mechanisms involved at the molecular level. Materials and methods: The main components of GDT were analyzed using ultra-performance liquid chromatography. TMT was used to induce neurotoxicity in microglial BV-2 cells and C57BL6 mice. GDT was administered at various doses to determine its neuroprotective and seizure inhibition effects. The inhibitory effects of GDT on TMT-induced apoptosis, inflammatory pathways, and oxidative stress pathways were determined in the mouse hippocampal tissues. Results: GDT contained emodin, chrysophanol, albiflorin, paeoniflorin, 6-gingerol, and liquiritin apioside. In microglial BV-2 cells treated with TMT, GDT showed dose-dependent neuroprotective effects. Oral administration of GDT five times for 2.5 days before and after TMT injection inhibited seizures at doses of 180 and 540 mg/kg and inhibited neuronal death in the hippocampus. In hippocampal tissues extracted from mice, GDT inhibited the protein expression of ionized calcium binding adaptor molecule 1, glial fibrillary acidic protein, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3, and phosphorylated nuclear factor (NF)-κB/total-NFκB ratio. Additionally, GDT inhibited the messenger RNA levels of tumor necrosis factor-α, inducible nitric oxide synthase, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, interleukin-1β, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1. Conclusion: This study's results imply that GDT might have neuroprotective potential in neurodegenerative diseases through neuronal death inhibition and anti-inflammatory and antioxidant mechanisms. Graphical abstract: Image 1