The anti-inflammatory effect of ferulic acid is via the modulation of NFκB-TNF-α-IL-6 and STAT1-PIAS1 signaling pathways in 2-methoxyethanol-induced testicular inflammation in rats
Olubisi E. Adeyi, Oluwatobi T. Somade, Babajide O. Ajayi, Adewale Segun James, Taiwo R. Adeboye, Daniel A. Olufemi, Ebunoluwa V. Oyinlola, Ebenezer T. Sanyaolu, Iyabode O. Mufutau
Abstract
Ferulic acid (FAC) is a component of plant cell walls, where it serves as a building block of lignin and pectin. As such, it is abundantly found in vegetables and other plants. In contrast, 2-methoxyethanol (2METH) is a testicular toxin commonly found in products used by humans. This study is aimed to investigate the effect of FAC on 2METH-induced testicular inflammation in rats. Four groups of 5 animals each were used: Group I served as the control, Group II was exposed to 2METH only (100 mg/kg), Group III was administered 2METH (100 mg/kg) plus FAC (50 mg/kg), and Group IV served as the FAC (50 mg/kg) only group. All administrations were done orally for 30 days. At the end of the study, rats administered 2METH only showed a significant increase in the testicular levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and nuclear factor κB (NF-κB), as well as RNA gene expressions of Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1), and suppressor of cytokine signaling 1 (SOCS1) compared to the control group. In contrast, treatment with FAC led to a significant decrease in the testicular levels of IL-6, TNF-α, iNOS, COX-2, NF-κB, and gene expression of STAT1, while significantly increasing the testicular gene expression of protein inhibitor of activated STAT 1 (PIAS1) compared to rats exposed to 2METH only. Based on the data gathered from this study, FAC demonstrated an anti-inflammatory effect by inhibiting the testicular activation of NF-κB through the downregulation of pro-inflammatory markers (IL-6, TNF-α, iNOS, and COX-2) and the inhibition of the STAT1-PIAS1 signaling pathway in rats.