ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1661706
This article is part of the Research TopicNeuroinflammation: Mechanisms and Therapeutic InterventionsView all 20 articles
Neuroprotective Synergy of Curcumin and Glycyrrhiza glabra in an Alzheimer's Model: Implications for Inflammation and Redox Pathways
Provisionally accepted
- Union Jiangbei Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province 430100, China, Wuhan, China
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Word count: 277 Objective:Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive impairment, amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, and chronic neuroinflammation. Despite symptomatic treatments, no current therapies halt disease progression. Traditional Chinese Medicine (TCM) offers potential multi-targeted interventions in complex diseases like AD. In this study, we evaluated the individual and combined neuroprotective effects of curcumin and Glycyrrhiza glabra in a D-galactose/sodium nitrite-induced mouse model of AD. Behavioral analysis, biochemical assays, and molecular profiling were conducted to assess cognitive function, inflammatory cytokine expression, oxidative stress, and AD-related protein levels. Methods: Mice were randomly assigned to five groups: control, AD model, curcumin-treated, Glycyrrhiza glabra-treated, and combination-treated groups. Cognitive function was assessed using the Morris water maze. Levels of neuroinflammatory cytokines (IL-6, TNF-α), AD-related proteins (APP, MAPT), oxidative stress (MDA), and antioxidant capacity (SOD) were evaluated via quantitative PCR and Western blotting. Results:Curcumin alone modestly improved spatial learning and reduced IL-6 (p < 0.05), whereas Glycyrrhiza glabra had limited effects. The combination therapy yielded the strongest outcomes, significantly reducing escape latency (p < 0.01), IL-6 and TNF-α levels (p < 0.01 and p < 0.05), and downregulating APP and MAPT expression. Additionally, oxidative damage was attenuated, as indicated by decreased MDA and elevated SOD activity (p < 0.001). Although direct measurement of TLR4/NF-κB phosphorylation was not performed, the observed anti-inflammatory and antioxidant effects suggest possible modulation of this pathway. Conclusion: Co-administration of curcumin and Glycyrrhiza glabra exerts synergistic neuroprotective effects by attenuating neuroinflammation, oxidative stress, and AD-related protein expression, surpassing monotherapy outcomes.These findings suggest a synergistic neuroprotective mechanism via modulation of TLR4/MyD88/NF-κB and redox pathways. This study provides preclinical evidence supporting the development of TCM-based combination strategies for AD intervention.
Keywords: Alzheimer's disease, Curcumin, Glycyrrhiza glabra, Neuroinflammation, Oxidative Stress, cognitive dysfunction
Received: 08 Jul 2025; Accepted: 25 Sep 2025.
Copyright: © 2025 LIU, DONG and YAN. 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: JIAN DONG, liyu19781111@126.com
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