Dietary phytochemicals targeting neuroinflammation: mechanisms, bioavailability and translational challenges
5 affiliations
- 1Department of Anatomy, Kasturba Medical College, Manipal Academy of Higher Education
- 2Department of Biotherapeutics Research, Manipal Academy of Higher Education
- 3Department of Anatomy, Manipal Tata Medical College, Manipal Academy of Higher Education
- 4Department of Pharmacology, Manipal Tata Medical College, Manipal Academy of Higher Education
- 5Department of Physiology, Kasturba Medical College, Manipal Academy of Higher Education
Abstract
Neuroinflammation and oxidative stress are among the most common and fundamental biochemical mechanisms underlying many neurological disorders, and both are promising therapeutic targets. Neuroinflammation and oxidative stress are bidirectional, and each could trigger and amplify the other. Since activated immune cells during neuroinflammation produce high levels of ROS, creating a vicious biochemical cycle, targeting neuroinflammation is an ideal opportunity to curtail both neuroinflammation and oxidative stress. The initiation and progression of neuroinflammation cause structural and functional damage to both neurons and glial cells in the central nervous system. Early intervention to inhibit neuroinflammation could prevent irreversible damage to the nervous tissue. The current application of glucocorticosteroids and nonsteroidal anti-inflammatory drugs in neurological disorders poses a risk of injury to the cardiovascular, gastrointestinal, respiratory, hepatic, and renal systems. Bioactive phytochemicals derived from dietary herbal medicines with demonstrated anti-inflammatory activity could serve as effective substitutes. Although very few of these phytochemicals have undergone clinical trials demonstrating efficacy and safety, several limitations, including lower bioavailability, solubility, and stability, hinder their clinical use. The purpose of this review is to identify preclinical data on multiple dietary bioactive phytochemicals with robust anti-neuroinflammatory effects that could be considered for clinical trials. Based on sufficient, efficacious, predominantly preclinical data, this review highlights the need for future modifications to enhance bioavailability while maintaining or improving therapeutic efficacy, with reduced systemic side effects, for these phytochemicals, rather than evaluating their potency in newer disease models or exploring new mechanisms. Further, prioritizing the identification of top-tier phytochemicals or their combinations that exhibit high bioavailability, optimal dosing, and proven long-term safety, while minimizing drug interactions and systemic toxicity through a standardized set of preclinical studies, is essential to manage chronic neuroinflammation with phytochemicals.
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BibTeX
@article{bhat2026dietary,
title = {{Dietary phytochemicals targeting neuroinflammation: mechanisms, bioavailability and translational challenges}},
author = {Kumar M. R. Bhat and Raghavendra Upadhya and Aashika Nayak and Anjaneyulu Konuri and Praveen Kumar S. E. and Murali Adiga and Vasanthalaxmi K Rao and Dinesh Upadhya},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1943126},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1943126/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dietary phytochemicals targeting neuroinflammation: mechanisms, bioavailability and translational challenges
AU - Kumar M. R. Bhat
AU - Raghavendra Upadhya
AU - Aashika Nayak
AU - Anjaneyulu Konuri
AU - Praveen Kumar S. E.
AU - Murali Adiga
AU - Vasanthalaxmi K Rao
AU - Dinesh Upadhya
PY - 2026
DA - 2026/10/26
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1943126
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1943126/full
AB - Neuroinflammation and oxidative stress are among the most common and fundamental biochemical mechanisms underlying many neurological disorders, and both are promising therapeutic targets. Neuroinflammation and oxidative stress are bidirectional, and each could trigger and amplify the other. Since activated immune cells during neuroinflammation produce high levels of ROS, creating a vicious biochemical cycle, targeting neuroinflammation is an ideal opportunity to curtail both neuroinflammation and oxidative stress. The initiation and progression of neuroinflammation cause structural and functional damage to both neurons and glial cells in the central nervous system. Early intervention to inhibit neuroinflammation could prevent irreversible damage to the nervous tissue. The current application of glucocorticosteroids and nonsteroidal anti-inflammatory drugs in neurological disorders poses a risk of injury to the cardiovascular, gastrointestinal, respiratory, hepatic, and renal systems. Bioactive phytochemicals derived from dietary herbal medicines with demonstrated anti-inflammatory activity could serve as effective substitutes. Although very few of these phytochemicals have undergone clinical trials demonstrating efficacy and safety, several limitations, including lower bioavailability, solubility, and stability, hinder their clinical use. The purpose of this review is to identify preclinical data on multiple dietary bioactive phytochemicals with robust anti-neuroinflammatory effects that could be considered for clinical trials. Based on sufficient, efficacious, predominantly preclinical data, this review highlights the need for future modifications to enhance bioavailability while maintaining or improving therapeutic efficacy, with reduced systemic side effects, for these phytochemicals, rather than evaluating their potency in newer disease models or exploring new mechanisms. Further, prioritizing the identification of top-tier phytochemicals or their combinations that exhibit high bioavailability, optimal dosing, and proven long-term safety, while minimizing drug interactions and systemic toxicity through a standardized set of preclinical studies, is essential to manage chronic neuroinflammation with phytochemicals.
SN - 1663-9812
ER -