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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Neuropharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1638068

This article is part of the Research TopicPharmacology of Natural Products against Neurodegenerative DisordersView all 17 articles

Spirodelae Herba ethanol extract attenuates neurotoxicity in hippocampal cells and improves scopolamine-induced cognitive impairment in mice

Provisionally accepted
  • 1Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of Korea
  • 2Hallym University Hangang Sacred Heart Hospital, Seoul, Republic of Korea
  • 3Kyungpook National University, Daegu, Republic of Korea

The final, formatted version of the article will be published soon.

Background: Spirodelae Herba (SH) is a herb that has been used in traditional medicine in East Asia. While its anti-inflammatory, anti-allergic, and antioxidant activities have recently been demonstrated, the effects of SH ethanol extract (SHE) on neurotoxicity in hippocampal neurons, neuroinflammation in microglia, and cognitive impairment in mice have not been studied. Methods: This study explored the protective effect of SHE on neurotoxicity related to oxidative stress and the related molecular mechanisms in a hippocampal cell model. We also examined the inhibitory effect of SHE on neuroinflammation and related mechanisms in endotoxin-stimulated microglia. We also explored the ameliorative effect of SH ethanol extract (SHE) on cognitive impairment in mice through behavioral tests and examined histopathological changes in the hippocampus and cortex using Nissl staining. In addition, we conducted a comprehensive analysis of the related mechanisms, including the microbiota-gut-brain axis. Results: SHE inhibited glutamate-induced neurotoxicity in HT22 cells and induced changes in related mechanisms. SHE effectively inhibited lipopolysaccharide-induced neuroinflammation in BV2 cells and regulated the activation of related mechanisms. Also, SHE administration significantly alleviated scopolamine (SCO)-induced decreases in memory and learning ability in mice. SHE suppressed damage to hippocampal neurons in the mice’s brain and significantly increased the expression of brain-derived neurotrophic factor and related pathway proteins in hippocampal tissue. Furthermore, microbiome analysis revealed that SHE administration normalized SCO-induced gut microbiota imbalance (dysbiosis). These findings indicate that the cognitive improvement effects of SHE may be mediated through the modulation of the gut microbiota composition and the microbiota–gut–brain axis. Conclusion: The results of this study demonstrate the neuroprotective and anti-neuroinflammatory effects of SHE and its strong potential as a preventive and therapeutic agent for cognitive impairment.

Keywords: Spirodelae Herba, Neuronal protection, antioxidant, Neuroinflammation, cognitive impairment, Microbiota-gut-brain axis

Received: 30 May 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Jeong, Jung, Li, Yang, Oh and Bae. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
You-Chang Oh, Korean Medicine Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of Korea
Jong-Sup Bae, Kyungpook National University, Daegu, Republic of Korea

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