Chlorogenic Acid Alleviates Chronic Stress-Induced Intestinal Damage by Inhibiting the P38MAPK/NF-κB Pathway

Abstract

Chronic stress can cause intestinal barrier damage. MAPK and NF-κB are closely related to it. Chlorogenic acid (CGA), a dietary polyphenol, has been shown to have intestinal protective effects, but whether by regulating MAPK and NF-κB is not known. Therefore, in this experiment, 24 Wistar rats were randomly divided into 4 groups (C group, CS group, CS + SB203580, and CS + CGA group). Rats in the CS group were restrained stress for 6 h per day for 21 days. Rats in the CS + SB203580 group were given SB203582 (0.5 mg/kg, intraperitoneal injection) 1 h before restraint stress every other day. Rats in the CS + CGA group were given CGA (100 mg/kg, gavage) 1 h before restraint stress. In chronic stress, intestinal barrier damage was evident, while being restored after CGA treatment. After chronic stress, the levels of p-P38 were increased (P < 0.01), while the levels of p-JNK and p-ERK were not changed. The levels of p-p38 were elevated after CGA treatment (P < 0.01). These results suggested that p38MAPK played an important role in chronic stress-induced intestinal injury, and CGA could inhibit p38MAPK activity. Therefore, we chose SB203582 (P38MAPK inhibitor) to elucidate the role of p38. After chronic stress, intestinal tight junction key proteins Occludin, ZO-1, and Claudin3 protein and gene expression were reduced (P < 0.01), while being elevated after CGA or SB203582 intervention (P < 0.05). After CGA treatment, the levels of p-IκB, p-p65, p-p38, and TNF-α were reduced (P < 0.01). SB203582 intervention reduced p-p65 and TNF-α levels significantly (P < 0.01). These results suggested that CGA could inhibit the NF-κB pathway by suppressing p38MAPK, thereby alleviating chronic stress-induced intestinal damage.

Antioxidant, Anti-Inflammatory and Pro-Differentiative Effects of Chlorogenic Acid on M03-13 Human Oligodendrocyte-like Cells

“…Many studies on CGA, carried out in vivo and in vitro on cell lines of the gastrointestinal tract and heart, have demonstrated its antioxidant and anti-inflammatory role. Studies on rats have shown that CGA inhibits the NF-κB pathway and suppresses p38 MAPK, alleviating intestinal damage induced by chronic stress [51]. Further studies have confirmed that in cardiomyocytes obtained from rats, CGA reduces chemotherapy-induced oxidative stress and apoptosis, through mechanisms involving Nrf2/HO-1 and dityrosine signaling [52].…”

Evaluating the Neuroprotective Potential of Caffeinated Coffee in the Context of Aluminum-Induced Neurotoxicity: Insights from a PC12 Cell Culture Model

“…Its activation increases along with the activation of MAPK (Al activates MAPK, as it was already mentioned in this paragraph) and leads to an elevation in the production of pro-inflammatory factors, potentially causing cell damage [ 78 ]. As indicated by the latest research, CGA inhibits NF-κB by suppressing p38 MAPK activation, contributing to the prevention of cell death [ 79 , 80 , 81 ]. It can be concluded that constituents of caffeinated coffee, likely primarily CGA, mitigate the neurotoxicity of Al and thus reduce the risk of neurodegenerative diseases development.…”