Ferulic Acid as an Anti-Inflammatory Agent: Insights into Molecular Mechanisms, Pharmacokinetics and Applications

Abstract

Ferulic acid (FA), a hydroxycinnamic acid derivative, is a key bioactive component in traditional medicinal plants including Angelica sinensis and Asafoetida. Accumulating evidence supports its therapeutic efficacy in inflammatory disorders, such as rheumatoid arthritis (RA) and ulcerative colitis (UC). FA exerts anti-inflammatory effects through (1) the regulation of inflammatory cytokine levels; (2) modulation of signaling pathways such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and janus kinase/signal transducer and activator of transcription (JAK/STAT); (3) amelioration of oxidative stress; and (4) regulation of immune cell homeostasis. At the pharmacokinetic level, studies show that FA is rapidly absorbed but exhibits low bioavailability, mainly due to the influence of metabolic pathways and food matrix characteristics. This review systematically summarizes the literature on the anti-inflammatory effects of FA, covering molecular mechanisms, pharmacokinetic characteristics, and application scenarios. Preclinical studies show that FA has low toxicity and good safety, demonstrating potential for development as a novel anti-inflammatory drug. However, its clinical translation is hindered by bottlenecks such as low bioavailability and insufficient human clinical data. Future research should prioritize developing novel drug delivery systems and conducting large-scale clinical trials to facilitate its clinical translation.

Keywords: anti-inflammatory mechanism; clinical translation; cytotoxicity; ferulic acid; inflammatory diseases; pharmacokinetics.

Figure 1

Chemical structure of FA.

Figure 2

Molecular Mechanisms of the Anti-inflammatory Effects of FA. (IL-1β: Interleukin-1β; caspase-1: Cysteine-aspartic protease 1; NLRP3: NOD-like receptor protein 3; FA: Ferulic acid; LPS: Lipopolysaccharide; TLR4: Toll-like receptor 4; TRAF: Tumor necrosis factor receptor associated factor; MyD88: Myeloid differentiation primary response protein 88; IKK: IkappaB kinase; NF-κB: Nuclear factor kappa B; PPARγ: Peroxisome proliferator-activated receptor gamma; AP-1: Activator protein 1; MAPKs: Mitogen-activated protein kinases; JNK: c-Jun N-terminal kinase; ERK: Extracellular regulated kinase; c-Jun: c-Jun proto-oncogene protein; c-Fos: c-Fos proto-oncogene protein; iNOs: Inducible nitric oxide synthase; ICAM-1: Intercellular adhesion molecule 1; VCAM-1: Vascular cell adhesion molecule 1; PTP1B: Protein tyrosine phosphatase 1B; AMPK: AMP-activated protein kinase; mTOR: Mammalian target of rapamycin; TNF-α: tumor necrosis factor-α; JAK: Janus kinase; STAT: Signal transducer and activator of transcription; TGF-β: Transforming growth factor-β; MCP-1: Monocyte chemoattractant protein-1; COX-2: Cyclooxygenase-2; CXCL2: C-X-C Chemokine Ligand 2).

Figure 3

Molecular Mechanisms of the Antioxidant Effects of FA. (FA: Ferulic acid; LPS: Lipopolysaccharide; TLR4: Toll-like receptor 4; ROS: Reactive oxygen species; NF-κB: Nuclear factor kappa B; Keap1: Kelch-like ECH-associated protein 1; Nrf2: Nuclear factor erythroid 2-related factor 2; HO-1: Heme oxygenase-1; ARE: Antioxidant response element; SOD: Superoxide dismutase; CAT: Catalase; GSH: Glutathione; PIP2: Phosphatidylinositol-4,5-bisphosphate; PIP3: Phosphatidylinositol-3,4,5-trisphosphate; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; mTOR: Mammalian target of rapamycin; AMPK: AMP-activated protein kinase; eNOS: Endothelial nitric oxide synthase; NO: Nitric oxide).