TY - JOUR
T1 - The mechanisms and therapeutic applications of phenolic acids in vascular cognitive impairment
T2 - A comprehensive review
AU - Zhang, Qiudong
AU - Shi, Yajun
AU - Zhang, Xingfang
AU - Liang, Shan
AU - Xu, Huailiang
AU - Quan, Wei
AU - Zhong, Chuanxin
AU - Ding, Yi
N1 - Funding information:
This work was supported by the National Natural Science Foundation of China [grant numbers: 82274313 and 82501062], the Key R&D Program of Xianyang (L2024-ZDYF-ZYF-SF-0060), the Hospital Pharmacy High Quality Development Project of Shaanxi Province (XM-2024–1–2–17), and Projects of Shaanxi Administration of Traditional Chinese Medicine (2022-SLRH-YQ-010) and Key Laboratory of Pharmacology of Traditional Chinese Medicine.
Publisher Copyright:
© 2025 The Author(s). Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.
PY - 2025/9/27
Y1 - 2025/9/27
N2 - Vascular cognitive impairment (VCI), the second most common form of cognitive dysfunction after Alzheimer's disease (AD), is characterized by a multifactorial pathogenesis involving cerebrovascular injury, neuroinflammatory responses, and oxidative stress-mediated neuronal damage. As a growing global health concern with limited treatment options, novel therapeutic strategies are urgently needed. Phenolic acids (PAs), a class of naturally occurring bioactive compounds widely found in plants, have shown great potential as therapeutic agents for VCI owing to their potent antioxidant, anti-inflammatory, and neuroprotective effects. The pleiotropic activities of VCI are particularly valuable for tackling the complex pathology of VCI. Preclinical studies have substantiated their efficacy in ameliorating cognitive deficits, but their favorable pharmacokinetic properties and synergistic interactions with existing therapeutic regimens underscore their strong translational potential for clinical applications. Nevertheless, significant challenges hinder the clinical translation of PAs, including unresolved issues regarding their systemic bioavailability and nonlinear dosesingle bond-response relationships, the unmet need for brain-targeted delivery systems to improve spatial precision, and the imperative to decipher their pleiotropic mechanisms via integrated multiomics approaches. Future investigations should adopt interdisciplinary strategies to propel the implementation of PAs in VCI precision medicine, encompassing advanced pharmacogenomics, nanodelivery platforms, and AI-driven target prediction. This review systematically summarizes the classification and structure–activity relationships of PAs, elucidating their molecular mechanisms in VCI therapy while critically examining the current opportunities and challenges in clinical translation. Its overarching aim is to accelerate the clinical application of PAs and to foster the development of innovative strategies for addressing VCI.
AB - Vascular cognitive impairment (VCI), the second most common form of cognitive dysfunction after Alzheimer's disease (AD), is characterized by a multifactorial pathogenesis involving cerebrovascular injury, neuroinflammatory responses, and oxidative stress-mediated neuronal damage. As a growing global health concern with limited treatment options, novel therapeutic strategies are urgently needed. Phenolic acids (PAs), a class of naturally occurring bioactive compounds widely found in plants, have shown great potential as therapeutic agents for VCI owing to their potent antioxidant, anti-inflammatory, and neuroprotective effects. The pleiotropic activities of VCI are particularly valuable for tackling the complex pathology of VCI. Preclinical studies have substantiated their efficacy in ameliorating cognitive deficits, but their favorable pharmacokinetic properties and synergistic interactions with existing therapeutic regimens underscore their strong translational potential for clinical applications. Nevertheless, significant challenges hinder the clinical translation of PAs, including unresolved issues regarding their systemic bioavailability and nonlinear dosesingle bond-response relationships, the unmet need for brain-targeted delivery systems to improve spatial precision, and the imperative to decipher their pleiotropic mechanisms via integrated multiomics approaches. Future investigations should adopt interdisciplinary strategies to propel the implementation of PAs in VCI precision medicine, encompassing advanced pharmacogenomics, nanodelivery platforms, and AI-driven target prediction. This review systematically summarizes the classification and structure–activity relationships of PAs, elucidating their molecular mechanisms in VCI therapy while critically examining the current opportunities and challenges in clinical translation. Its overarching aim is to accelerate the clinical application of PAs and to foster the development of innovative strategies for addressing VCI.
KW - blood-brain barrier
KW - neuroprotection
KW - oxidative stress
KW - Phenolic acids
KW - therapeutic applications
KW - vascular cognitive impairment
UR - https://www.scopus.com/pages/publications/105020931823
UR - https://www.sciencedirect.com/science/article/pii/S1874467225000078?via%3Dihub#sec0125
U2 - 10.1016/j.cmp.2025.09.002
DO - 10.1016/j.cmp.2025.09.002
M3 - Journal article
AN - SCOPUS:105020931823
SN - 1874-4672
VL - 18
SP - 32
EP - 47
JO - Current Molecular Pharmacology
JF - Current Molecular Pharmacology
IS - 1
ER -
