ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Identification, Biotransformation, and Neuroprotective Potential of the Ethanol Extract of Alpiniae Oxyphyllae Fructus in Neuroinflammation-Related Cognitive Impairment
Provisionally accepted
Zirong Yi1Xinyu Wang1Lin Wang2Renfang Yin2
Dongying Qi1Huan Liu1Yuxin Chen1Yamei Xie1Yuming Ma1Mengqi Hu1Nan Zhang1Yanli Pan2*
Yang Liu1*
Guopeng Wang3*- 1Beijing University of Chinese Medicine School of Chinese Materia Medica, Beijing, China
- 2Institute of Information on Traditional Chinese Medicine China Academy of Chinese Medical Sciences, Beijing, China
- 3Zhongcai Health (Beijing) Biological Technology Development Co., Ltd., Beijing, China
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Background: Neuroinflammation is a key pathological mechanism underlying various central nervous system (CNS) disorders. Alpiniae Oxyphyllae Fructus (AOF), the dried fruit of Alpinia oxyphylla, has shown therapeutic potential for these disorders. This study aimed to characterize the chemical constituents, biotransformation profiles, and neuroprotective potential of the ethanol extract of AOF in neuroinflammation-related cognitive impairment. Methods: The ethanol extract of AOF was analyzed using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) and Global Natural Products Social Molecular Networking (GNPS). Sequential metabolism experiments were performed to investigate its dynamic biotransformation and blood–brain barrier (BBB) permeability. Neuroprotective effects of sesquiterpenoid-enriched fractions from AOF (SE-AOF) were evaluated in a lipopolysaccharide (LPS)-induced mouse model of neuroinflammation-associated cognitive impairment. Results: A total of 108 bioactive compounds were identified from the ethanol extract of AOF. Among them, 34 compounds, mainly sesquiterpenoids, were also detected in the cerebrospinal fluid and brain tissue, indicating BBB penetration. SE-AOF significantly improved cognitive function, reduced inflammatory cytokine levels, and alleviated oxidative stress in plasma and brain tissues of LPS-treated mice. Conclusion: These findings demonstrate that the ethanol extract of AOF exerted neuroprotective effects via its bioactive sesquiterpenoids, providing insights into the therapeutic potential of natural products (NPs) against neuroinflammation-related CNS disorders.
Keywords: Alpiniae oxyphyllae Fructus, Sesquiterpenoids, GNPs, sequential metabolism method, blood-brain barrier permeability, Anti-neuroinflammation
Received: 27 Sep 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Yi, Wang, Wang, Yin, Qi, Liu, Chen, Xie, Ma, Hu, Zhang, Pan, Liu and Wang. 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:
Yanli Pan, panyl@mail.cintcm.ac.cn
Yang Liu, liuyang@bucm.edu.cn
Guopeng Wang, binglelly@163.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.