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Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review)

  • Authors:
    • Xiaoyan Xue
    • Yongchang Lai
    • Shasha Song
    • Liping Wu
    • Lifang Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Ganzhou Hospital‑Nanfang Hospital, Southern Medical University (Ganzhou People's Hospital), Ganzhou, Jiangxi 341099, P.R. China, Department of Pharmaceutical Administration, School of Medical Business, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China, Department of Pharmacy, Ganzhou Hospital‑Nanfang Hospital, Southern Medical University (Ganzhou People's Hospital), Ganzhou, Jiangxi 341099, P.R. China
    Copyright: © Xue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 211
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    Published online on: May 29, 2026
       https://doi.org/10.3892/mmr.2026.13921
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Abstract

Neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, anxiety and depression pose significant global public health challenges due to their high prevalence and complex pathological mechanisms. Current therapeutic strategies primarily offer symptomatic relief, with limited efficacy in mitigating disease progression. Neuroprotection involves interventions aimed at preserving neuronal structure and function through mechanisms such as reducing oxidative stress, modulating inflammation and inhibiting apoptosis, presenting a promising avenue for treating these conditions. Protocatechuic acid (PCA), a natural phenolic acid compound prevalent in a variety of foods and herbal medicines, has received considerable attention for its notable antioxidant, anti‑inflammatory and neuroprotective properties. The present study systematically reviews the neuroprotective effects and molecular mechanisms of PCA in various neurological disorders (including AD, PD and cerebral ischemia). The present review highlights the multi‑target mechanisms of PCA, which act by mitigating oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis, while promoting neuronal regeneration. Furthermore, the present review integrates the body of evidence across neurological contexts to identify conserved protective pathways and discusses the translational potential of PCA, providing a foundation for its clinical application in treating neurological diseases.
View Figures

Figure 1

Interaction among
neuroprotection-related pathways. Abnormal protein aggregation,
toxin-induced nerve injury through REDOX homeostasis modulation,
the neurotrophic factor/TrkB/PI3K/Akt pathway, glutamate-mediated
excitotoxicity, microglia activation and mitochondrial dysfunction
are the basis of the crosstalk among CNS injury-related molecules.
CNS, central nervous system; α-syn, α-synuclein; Aβ, amyloid-β;
mHTT, mutant huntingtin; TDP-43, TAR DNA-binding protein 43; ROS,
reactive oxygen species; TrkB, tropomyosin receptor kinase B; GDNF,
glial cell line-derived neurotrophic factor; MDA, malondialdehyde;
BBB, blood-brain barrier; BDNF, brain-derived neurotrophic factor;
NGF, nerve neurotrophic factor; 5-HT, 5-hydroxytryptamine; DA,
dopamine; NE, norepinephrine; TNF-α, tumor necrosis factor-α; IL,
interleukin-6.

Figure 2

Roles and mechanisms of PCA in
neuroprotection-related signaling pathways. Antioxidant activity,
anti-inflammatory modulation, anti-apoptotic regulation,
mitochondrial protection and homeostasis maintenance of PCA are
summarized. PCA, protocatechuic acid; TNF-α, tumor necrosis
factor-α; IL, interleukin-6; IκB, inhibitor of nuclear factor-κB;
NF-κB, nuclear factor-κB; AKT, protein kinase B; MAPK,
mitogen-activated protein kinases; ERK, extracellular regulated
protein kinases; PI3K, phosphatidylinositol-4,5-bisphosphate
3-kinase; α-syn, α-synuclein; Aβ, amyloid-β; BDNF, brain-derived
neurotrophic factor; TrkB, tropomyosin receptor kinase B; ROS,
reactive oxygen species.
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Xue X, Lai Y, Song S, Wu L and Wang L: Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review). Mol Med Rep 34: 211, 2026.
APA
Xue, X., Lai, Y., Song, S., Wu, L., & Wang, L. (2026). Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review). Molecular Medicine Reports, 34, 211. https://doi.org/10.3892/mmr.2026.13921
MLA
Xue, X., Lai, Y., Song, S., Wu, L., Wang, L."Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review)". Molecular Medicine Reports 34.1 (2026): 211.
Chicago
Xue, X., Lai, Y., Song, S., Wu, L., Wang, L."Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review)". Molecular Medicine Reports 34, no. 1 (2026): 211. https://doi.org/10.3892/mmr.2026.13921
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Spandidos Publications style
Xue X, Lai Y, Song S, Wu L and Wang L: Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review). Mol Med Rep 34: 211, 2026.
APA
Xue, X., Lai, Y., Song, S., Wu, L., & Wang, L. (2026). Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review). Molecular Medicine Reports, 34, 211. https://doi.org/10.3892/mmr.2026.13921
MLA
Xue, X., Lai, Y., Song, S., Wu, L., Wang, L."Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review)". Molecular Medicine Reports 34.1 (2026): 211.
Chicago
Xue, X., Lai, Y., Song, S., Wu, L., Wang, L."Elucidating the multitarget neuroprotective mechanisms of protocatechuic acid in neurological disorders (Review)". Molecular Medicine Reports 34, no. 1 (2026): 211. https://doi.org/10.3892/mmr.2026.13921
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