Gentiopicroside Attenuates Lithium/Pilocarpine-Induced Epilepsy Seizures by Down-Regulating NR2B/CaMKII/CREB and TLR4/NF-κB Signaling Pathways in the Hippocampus of Mice.

Autor: Tian MM; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Liu G; New Drug Screening Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China., Du J; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Liu Y; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Wei W; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Lan XB; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Hai DM; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Ma L; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Yu JQ; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China., Liu N; School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China.; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Yinchuan 750004, China.; Colaborative Innovation Center for Ningxia Characteristic Traditional Chinese Medicine by Ningxia Hui Autonomous Region & Education Ministry of P.R. China, Yinchuan 750004, China.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 Oct 22; Vol. 17 (11). Date of Electronic Publication: 2024 Oct 22.
DOI: 10.3390/ph17111413
Abstrakt: Background: Epilepsy is a prevalent and disabling neurological condition characterized by recurrent seizures. Approximately 50% of adults with active epilepsy have at least one comorbidity and they are at a greater risk of premature death than the general population. Gentiopicroside (Gent) is a primary component of Gentiana macrophylla Pall. that has been shown to have diverse pharmacological properties. However, its role in epileptic seizures in adult mice and its underlying mechanism of action remain obscure. We aimed to explore the anti-epileptic effect and mechanism of Gent on lithium/pilocarpine (Pilo)-induced epilepsy seizures in mice. Methods: In this study, we established a lithium/Pilo-induced epilepsy model, and Gent was first given to mice 30 min before Pilo administration. Then, we detected behavioral and histopathological changes through electrocorticographic (ECoG) measurements, Nissl staining, Fluoro-Jade B (FJB) staining, and immunohistochemical staining. We then used molecular biology techniques, such as Western blotting, quantitative polymerase chain reaction (qPCR) analysis, and the enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms of Gent in lithium/Pilo-induced epileptic seizures in mice and lipopolysaccharide (LPS)-induced inflammatory astrocytes. Results: We confirmed that Gent could prevent abnormal ECoG activity, behavioral changes, and neurodegeneration. Subsequently, we found Gent could downregulate the factors that could promote apoptosis (i.e., the NR2B/CaMKII/CREB signaling cascade) and neuroinflammatory-related factors (i.e., the TLR4/NF-κB signaling cascade). Conclusions: Gent could be a potential therapeutic agent for epilepsy, offering possibilities for both prevention and treatment. Our research establishes a preliminary experimental framework for ongoing studies into Gent's efficacy as a treatment for epilepsy.
Databáze: MEDLINE
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