Schematic drawing presenting signaling pathways affected by ferulic acid

A schematic drawing presenting signaling pathways affected by ferulic acid. (A) Under normal conditions, Nrf2 is sequestered in cytoplasm by keap1. Ferulic acid (FA) induces the translocation of Nrf2 from the cytoplasm to the nucleus and promotes the expression of Nrf2, which activates antioxidant response element (ARE) and increases transcription of Nrf2-regulated genes, such as HO-1. FA activates the Nrf2/HO-1 signaling, exerting an anti-oxidative effect. (B) The process of activating p38 MAPK and NF-κB signal cascades through TLR4 signaling, leading to the expression of inflammatory cytokines. NF-κB signaling requires IKK subunits, which regulate pathway activation through IκB phosphorylation. The JAK/STAT signaling pathway is activated by cytokines and STATs are dephosphorylated in the nucleus, leading to the activation of downstream inflammatory cytokines. FA acts as an anti-inflammatory agent by inhibiting the p38 MAPK, NF-κB, and JAK/STAT pathways. (C) FA can block the activation of TGF-β1/Smads signaling and reverse the nuclear translocation of Smads to resist fibrosis. Furthermore, FA has the ability to alleviate ECM by regulating MMPs. (D) FA promotes tumor regression and cell apoptosis by increasing the expression of p53 and Bax, while inhibiting proliferation by decreasing the expression of ERK and AKT. AKT: protein kinase B; Bax: Bcl2-associated X protein; ECM: extracellular matrix; ERK: extracellular signal-regulated kinase; HO-1: heme oxygenase-1; IκB: inhibitor of NF-κB; IKK: IkappaB kinase; JAK: Janus kinase; Keap1: Kelch-like-ECH-associated protein 1; MAPK: mitogen-activated protein kinase; MMPs: matrix metalloproteinases; NF-κB: nuclear factor-kappaB; Nrf2: nuclear factor erythroid-2-related factor-2; Smads: small mothers against decapentaplegics; STAT: signal transducer and activator of transcription; TGF-β1: transforming growth factor-β1; TLR4: toll-like receptor 4.

Publication

Ferulic Acid: A Review of Pharmacology, Toxicology, and Therapeutic Effects on Pulmonary Diseases (2023) Yiman Zhai, et al. Int J Mol Sci. 2023 May;24(9). Figure: F2. Homo sapiens

Disease mentions