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

Artemisinin is a sesquiterpene lactone derived from the plant <i>Artemisia annua</i> 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. R...

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Main Authors: Sergey A. Pukhov, Alexey V. Semakov, Nadezhda E. Pukaeva, Olga A. Kukharskaya, Tatyana V. Ivanova, Viktoriya S. Kryshkova, Sergey O. Bachurin, Michail S. Kukharsky
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Language:English
Published: MDPI AG 2025-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/1/198
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author Sergey A. Pukhov
Alexey V. Semakov
Nadezhda E. Pukaeva
Olga A. Kukharskaya
Tatyana V. Ivanova
Viktoriya S. Kryshkova
Sergey O. Bachurin
Michail S. Kukharsky
author_facet Sergey A. Pukhov
Alexey V. Semakov
Nadezhda E. Pukaeva
Olga A. Kukharskaya
Tatyana V. Ivanova
Viktoriya S. Kryshkova
Sergey O. Bachurin
Michail S. Kukharsky
author_sort Sergey A. Pukhov
collection DOAJ
description Artemisinin is a sesquiterpene lactone derived from the plant <i>Artemisia annua</i> 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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spelling doaj-art-a303b26759054f5d8423e149d2b51d762025-01-10T13:19:10ZengMDPI AGMolecules1420-30492025-01-0130119810.3390/molecules30010198Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In VitroSergey A. Pukhov0Alexey V. Semakov1Nadezhda E. Pukaeva2Olga A. Kukharskaya3Tatyana V. Ivanova4Viktoriya S. Kryshkova5Sergey O. Bachurin6Michail S. Kukharsky7Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaInstitute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaInstitute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaInstitute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaDepartment of General and Cell Biology, Faculty of Medical Biology, Pirogov Russian National Research Medical University, 117997 Moscow, RussiaInstitute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaInstitute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaInstitute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, RussiaArtemisinin is a sesquiterpene lactone derived from the plant <i>Artemisia annua</i> 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.https://www.mdpi.com/1420-3049/30/1/198artemisininsesquiterpene lactoneneuroprotectionneurodegenerationER stressaggregation
spellingShingle Sergey A. Pukhov
Alexey V. Semakov
Nadezhda E. Pukaeva
Olga A. Kukharskaya
Tatyana V. Ivanova
Viktoriya S. Kryshkova
Sergey O. Bachurin
Michail S. Kukharsky
Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro
Molecules
artemisinin
sesquiterpene lactone
neuroprotection
neurodegeneration
ER stress
aggregation
title Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro
title_full Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro
title_fullStr Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro
title_full_unstemmed Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro
title_short Artemisinin Stimulates Neuronal Cell Viability and Possess a Neuroprotective Effect In Vitro
title_sort artemisinin stimulates neuronal cell viability and possess a neuroprotective effect in vitro
topic artemisinin
sesquiterpene lactone
neuroprotection
neurodegeneration
ER stress
aggregation
url https://www.mdpi.com/1420-3049/30/1/198
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