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Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro.

Title: Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro.
Authors: Pukhov SA; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Department of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.; Semakov AV; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Pukaeva NE; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Department of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.; Kukharskaya OA; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Department of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.; Ivanova TV; Department of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.; Kryshkova VS; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Department of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.; Bachurin SO; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Kukharsky MS; Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Russia.; Department of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Source: Molecules (Basel, Switzerland) [Molecules] 2025 Jan 06; Vol. 30 (1). Date of Electronic Publication: 2025 Jan 06.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, c1995-
MeSH Terms: Artemisinins*/pharmacology ; Artemisinins*/chemistry ; Neuroprotective Agents*/pharmacology ; Neuroprotective Agents*/chemistry ; Neurons*/drug effects ; Neurons*/metabolism ; Neurons*/cytology; Cell Survival/drug effects ; Endoplasmic Reticulum Stress/drug effects ; Oxidative Stress/drug effects ; Hippocampus/cytology ; Hippocampus/drug effects ; Humans ; HEK293 Cells ; Animals ; Cell Line, Tumor
Abstract: Artemisinin is a sesquiterpene lactone derived from the plant Artemisia annua L., renowned for its antimalarial activity. Based on this compound, various derivatives and analogues have been obtained that exhibit diverse biological activities, including clinically approved drugs. Recently, increasing evidence has highlighted the neuroprotective potential of artemisinin. In this study, we evaluated the effects of artemisinin on the viability of neuronal-like cells, including primary hippocampal neuronal cultures. Artemisinin exhibited a stimulating effect on SH-SY5Y and HEK-293 cells and enhanced the survival of primary neurons at low concentrations (1 µM). In contrast, artemisinin derivatives, such as dihydroartemisinin, anhydrodihydroartemisinin, and artemisitene, did not display similar stimulatory activity, suggesting that the intact lactone ring is crucial for this property. Furthermore, artemisinin demonstrated a protective effect against endoplasmic reticulum (ER) stress induced by the proteasome inhibitor MG132 in SH-SY5Y cells. However, it did not exhibit protective activity against oxidative stress induced by sodium arsenite. Additionally, artemisinin effectively inhibited the aggregation of mutated TDP-43 protein in transfected SH-SY5Y cells. These findings suggest that artemisinin exerts neuroprotective effects by targeting key molecular pathways associated with neurodegeneration, offering potential therapeutic insights for related conditions.
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Grant Information: FFSG-2024-0023 IPAC RAS State Target
Contributed Indexing: Keywords: ER stress; aggregation; artemisinin; neurodegeneration; neuroprotection; sesquiterpene lactone
Substance Nomenclature: 0 (Artemisinins); 0 (Neuroprotective Agents); 9RMU91N5K2 (artemisinin)
Entry Date(s): Date Created: 20250111 Date Completed: 20250430 Latest Revision: 20250521
Update Code: 20260130
PubMed Central ID: PMC11723108
DOI: 10.3390/molecules30010198
PMID: 39795253
Database: MEDLINE

Journal Article