# Research progress on the molecular mechanisms of chlorogenic acid’s pharmacological effects and its advanced drug delivery systems

**Authors:** Linran Gao, Tianci Zhang, Xianyu Zhang, Wenbo Ding, Jianyu Yang, Yu Luo, Jingjing Wang, Xin Yuan, Yundong Zhao

PMC · DOI: 10.3389/fphar.2026.1746172 · Frontiers in Pharmacology · 2026-03-18

## TL;DR

This review explores how chlorogenic acid works in the body and new delivery methods to improve its effectiveness as a drug.

## Contribution

The paper highlights novel drug delivery systems to overcome bioavailability issues of chlorogenic acid.

## Key findings

- Chlorogenic acid modulates TLR2/NF-κB and MAPK pathways to exert anti-inflammatory effects.
- Drug delivery systems like nanoparticles and liposomes improve CGA stability and bioavailability.
- CGA shows therapeutic potential for hypertension, atherosclerosis, and metabolic disorders.

## Abstract

Chlorogic acid (CGA), a prevalent polyphenol formed in plants, is recognized for its broad spectrum of biological activities, including potent antioxidant, anti-inflammatory, antimicrobial, andmetabolic regulatory effects. This review synthesizes evidence demonstrating CGA’s therapeutic potential across various conditions, such as hypertension, gout, atherosclerosis, and metabolic disorders. Key mechanisms involve neutralizing reactive oxygen species, modulating critical signaling pathways like TLR2/NF-κB and MAPK, enhancing insulin sensitivity, and influencing endothelial function by boosting NO production via eNOS phosphorylation. Despite these promising attributes, CGA’s clinical translation is hindered by significant bioavailability challenges stemming from poor solubility, rapid metabolism, and instability in physiological environments. To address these limitations, innovative drug delivery systems are being investigated. These systems, including polymeric nanoparticles, liposomes, micelles, and hydrogels, offer strategies to encapsulate CGA, thereby protecting it from degradation, improving its dissolution properties, and enabling controlled or targeted release at specific sites of action. Such advancements in delivery technology are crucial for enhancing CGA’s stability and bioavailability, ultimately bridging the gap between its demonstrated in vitro and preclinical efficacy and its realization as an effective therapeutic agent in human medicine.

## Linked entities

- **Proteins:** NOS3 (nitric oxide synthase 3)
- **Chemicals:** chlorogenic acid (PubChem CID 1794427), NO (PubChem CID 24822)
- **Diseases:** gout (MONDO:0005393), atherosclerosis (MONDO:0005311)

## Full-text entities

- **Genes:** NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** inflammatory (MESH:D007249), atherosclerosis (MESH:D050197), gout (MESH:D006073), hypertension (MESH:D006973), metabolic disorders (MESH:D008659)
- **Chemicals:** chlorogenic acid (MESH:D002726), polyphenol (MESH:D059808), NO (MESH:D009614), CGA (-), reactive oxygen species (MESH:D017382)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13038915/full.md

## References

140 references — full list in the complete paper: https://tomesphere.com/paper/PMC13038915/full.md

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Source: https://tomesphere.com/paper/PMC13038915