Cis-Nerolidol Inhibits MAP Kinase and NF-κB Signaling Pathways and Prevents Epithelial Tight Junction Dysfunction in Colon Inflammation: In Vivo and In Vitro Studies

Abstract

Inflammation of the GI tract leads to compromised epithelial barrier integrity, which increases intestine permeability. A compromised intestinal barrier is a critical event that leads to microbe entry and promotes inflammatory responses. Inflammatory bowel diseases that comprise Crohn’s disease (CD) and ulcerative colitis (UC) show an increase in intestinal permeability. Nerolidol (NED), a naturally occurring sesquiterpene alcohol, has potent anti-inflammatory properties in preclinical models of colon inflammation. In this study, we investigated the effect of NED on MAPKs, NF-κB signaling pathways, and intestine epithelial tight junction physiology using in vivo and in vitro models. The effect of NED on proinflammatory cytokine release and MAPK and NF-κB signaling pathways were evaluated using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages. Subsequently, the role of NED on MAPKs, NF-κB signaling, and the intestine tight junction integrity were assessed using DSS-induced colitis and LPS-stimulated Caco-2 cell culture models. Our result indicates that NED pre-treatment significantly inhibited proinflammatory cytokine release, expression of proteins involved in MAP kinase, and NF-κB signaling pathways in LPS-stimulated RAW macrophages and DSS-induced colitis. Furthermore, NED treatment significantly decreased FITC-dextran permeability in DSS-induced colitis. NED treatment enhanced tight junction protein expression (claudin-1, 3, 7, and occludin). Time-dependent increases in transepithelial electrical resistance (TEER) measurements reflect the formation of healthy tight junctions in the Caco-2 monolayer. LPS-stimulated Caco-2 showed a significant decrease in TEER. However, NED pre-treatment significantly prevented the fall in TEER measurements, indicating its protective role. In conclusion, NED significantly decreased MAPK and NF-κB signaling pathways and decreased tight junction permeability by enhancing epithelial tight junction protein expression.

Integrated HS-GC–IMS and UPLC-Q-Orbitrap HRMS-based metabolomics revealed the characteristics and differential volatile and nonvolatile metabolites of different citrus peels

“…3-Hydroxy-2-butanone can serve as the characteristic compound of BZH, while methyl 2-nonynoate and nerolidol can serve the same purpose for CLU. Nerolidol is used medicinally to treat colon cancer and can also be used in cosmetics and food regulators ( Chan et al, 2016 ; Raj et al, 2023 ; Zhao et al, 2023 ). 1-Nonanol, 1-hexanol, 2-methylpropan-1-ol, and 1-heptanol can be used as characteristic compounds of QJ and XC.…”

Gallic acid attenuates LPS-induced inflammation in Caco-2 cells by suppressing the activation of the NF-κB/MAPK signaling pathway

“…LPS-stimulated cells can activate ERK, JNK and p38 and subsequently act on their substrates to affect the activity of various transcription factors, thus regulating the expressions of diverse cytokines, including TNF, IL-6 and IL-8. Therefore, it can trigger an inflammatory response in the colon through ERK, JNK and p38 [ 61 , 62 ]. In previous studies, several herbal ingredients, such as Ganoderma lucidum polysaccharide, were shown to relieve colitis through the MAPK signaling pathway [63] .…”

Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells

“…The inhibitory effect on the NF-κB pathway can significantly suppress the secretion of inflammatory indicators [35][36][37]; the inhibitory effect on the NF-κB pathways is considered an effective approach to control the occurrence and development of inflammatory diseases [38].…”