Xanthatin‐13‐(Pyrrolidine‐2‐Carboxylic Acid), a Sesquiterpene Lactone Isolated From Burdock Leaf, Attenuated Aβ 25‐35 Toxicity and Memory Deficits in a Pharmacological Mouse Model of Alzheimer's Disease
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2026
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| author | Charlyne Barry‐Simonnet Lucie Crouzier Tristan Moujellil‐Legagneur Hamza Chaieb‐Errass Yanis A. Idres Karine Ferrare Marc Rolland Guillaume Cazals Patrick Poucheret Tangui Maurice Didier Tousch |
| author_facet | Charlyne Barry‐Simonnet Lucie Crouzier Tristan Moujellil‐Legagneur Hamza Chaieb‐Errass Yanis A. Idres Karine Ferrare Marc Rolland Guillaume Cazals Patrick Poucheret Tangui Maurice Didier Tousch Charlyne Barry‐Simonnet Lucie Crouzier Tristan Moujellil‐Legagneur Hamza Chaieb‐Errass Yanis A. Idres Karine Ferrare Marc Rolland Guillaume Cazals Patrick Poucheret Tangui Maurice Didier Tousch |
| collection | Wiley Open Access |
| contents | Xanthatin‐13‐(Pyrrolidine‐2‐Carboxylic Acid), a Sesquiterpene Lactone Isolated From Burdock Leaf, Attenuated Aβ 25‐35 Toxicity and Memory Deficits in a Pharmacological Mouse Model of Alzheimer's Disease Charlyne Barry‐Simonnet Lucie Crouzier Tristan Moujellil‐Legagneur Hamza Chaieb‐Errass Yanis A. Idres Karine Ferrare Marc Rolland Guillaume Cazals Patrick Poucheret Tangui Maurice Didier Tousch Phytotherapy Research ABSTRACT Alzheimer's disease (AD) is a severe form of dementia, which occurrence increases with age and lifestyle conditions. It is characterized by amyloid protein accumulation forming senile plaques, hyperphosphorylated tau protein forming neurofibrillary tangles, neuroinflammation, and oxidative stress, leading to synapse loss and cell death. Pharmacological alternatives to conventional treatments include alkaloids with anti‐inflammatory and antioxidant properties. Sesquiterpene lactones, such as Xanthatin‐13‐(pyrrolidine‐2‐carboxylic acid) (XPc) from burdock leaf, show promise due to their antioxidant activity targeting glucose‐6‐phosphate dehydrogenase. This study evaluated XPc's protective effects in vivo using Aβ 25‐35 ‐treated mice, a pharmacological AD model, and explores its synergistic potential with neuroprotective agents like TSPO activators or sigma‐1 receptor agonists. Mice were administered Aβ 25‐35 peptide (9 nmol ICV) and XPc (0.3–3 mg/kg) daily for 4 days. Behavioral tests assessed memory deficits and anxiety. Post‐sacrifice, brains were analyzed for neuroinflammation and oxidative stress markers. Combination studies involved XPc with the TSPO activator PK11195 or the sigma‐1 receptor agonist PRE‐084, with memory evaluated in two behavioral tests. Combination indices were calculated to assess synergy. XPc (1–3 mg/kg) prevented Aβ 25‐35 ‐induced memory impairments and anxiety. It reduced astroglial reaction, blocked microglial activation, and confirmed antioxidant activity by lowering lipid peroxidation and protein nitrosylation. Combinations with PK11195 or PRE‐084 showed synergistic protection in memory tests. XPc is a potent neuroprotective agent against AD‐like toxicity in this murine model, effective alone or in synergistic combinations with other drugs. 10.1002/ptr.70294 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/ptr.70294 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_70294 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Xanthatin‐13‐(Pyrrolidine‐2‐Carboxylic Acid), a Sesquiterpene Lactone Isolated From Burdock Leaf, Attenuated Aβ 25‐35 Toxicity and Memory Deficits in a Pharmacological Mouse Model of Alzheimer's Disease Charlyne Barry‐Simonnet Lucie Crouzier Tristan Moujellil‐Legagneur Hamza Chaieb‐Errass Yanis A. Idres Karine Ferrare Marc Rolland Guillaume Cazals Patrick Poucheret Tangui Maurice Didier Tousch Phytotherapy Research Xanthatin‐13‐(Pyrrolidine‐2‐Carboxylic Acid), a Sesquiterpene Lactone Isolated From Burdock Leaf, Attenuated Aβ 25‐35 Toxicity and Memory Deficits in a Pharmacological Mouse Model of Alzheimer's Disease Charlyne Barry‐Simonnet Lucie Crouzier Tristan Moujellil‐Legagneur Hamza Chaieb‐Errass Yanis A. Idres Karine Ferrare Marc Rolland Guillaume Cazals Patrick Poucheret Tangui Maurice Didier Tousch Phytotherapy Research ABSTRACT Alzheimer's disease (AD) is a severe form of dementia, which occurrence increases with age and lifestyle conditions. It is characterized by amyloid protein accumulation forming senile plaques, hyperphosphorylated tau protein forming neurofibrillary tangles, neuroinflammation, and oxidative stress, leading to synapse loss and cell death. Pharmacological alternatives to conventional treatments include alkaloids with anti‐inflammatory and antioxidant properties. Sesquiterpene lactones, such as Xanthatin‐13‐(pyrrolidine‐2‐carboxylic acid) (XPc) from burdock leaf, show promise due to their antioxidant activity targeting glucose‐6‐phosphate dehydrogenase. This study evaluated XPc's protective effects in vivo using Aβ 25‐35 ‐treated mice, a pharmacological AD model, and explores its synergistic potential with neuroprotective agents like TSPO activators or sigma‐1 receptor agonists. Mice were administered Aβ 25‐35 peptide (9 nmol ICV) and XPc (0.3–3 mg/kg) daily for 4 days. Behavioral tests assessed memory deficits and anxiety. Post‐sacrifice, brains were analyzed for neuroinflammation and oxidative stress markers. Combination studies involved XPc with the TSPO activator PK11195 or the sigma‐1 receptor agonist PRE‐084, with memory evaluated in two behavioral tests. Combination indices were calculated to assess synergy. XPc (1–3 mg/kg) prevented Aβ 25‐35 ‐induced memory impairments and anxiety. It reduced astroglial reaction, blocked microglial activation, and confirmed antioxidant activity by lowering lipid peroxidation and protein nitrosylation. Combinations with PK11195 or PRE‐084 showed synergistic protection in memory tests. XPc is a potent neuroprotective agent against AD‐like toxicity in this murine model, effective alone or in synergistic combinations with other drugs. 10.1002/ptr.70294 http://creativecommons.org/licenses/by/4.0/ |
| title | Xanthatin‐13‐(Pyrrolidine‐2‐Carboxylic Acid), a Sesquiterpene Lactone Isolated From Burdock Leaf, Attenuated Aβ 25‐35 Toxicity and Memory Deficits in a Pharmacological Mouse Model of Alzheimer's Disease |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.70294 |