Juglone Mediates Inflammatory Bowel Disease Through Inhibition of TLR-4/NF KappaB Pathway in Acetic Acid-induced Colitis in Rats

Abstract

Background: Juglone is a phenolic bioactive compound with antimicrobial, anti tumour, antioxidant, and anti inflammatory characteristics. Given its anti inflammatory and an-tioxidant effects, it was selected for evaluation in the inflammatory bowel diseases (IBD) model. Objective: The current study was performed to evaluate the therapeutic impacts of the juglone in acetic acid induced colitis in male Wistar rats. Methods: Juglone was extracted from Pterocarya fraxinifolia via maceration method. Colitis was induced in 36 male Wistar rats (n = 6), except in the sham group, 1 ml of acetic acid 4% was administered intrarectally. Twenty four hours after induction of colitis, in 3 groups, juglone was administered orally (gavage) at 3 doses of 50, 100, and 150 mg/kg for 2 successive days (once a day). Other groups included the control group (only treated with acetic acid), sham group (nor-mal saline), and standard group (Dexamethasone). To evaluate the inflammation sites, macro-scopic and microscopic markers were assessed. The mRNA expression of interleukin ( 1β, and tumor necrosis factor alpha ( α were assessed by real time PCR, while myeloperoxidase (MPO) was measured spectrophotometrically. ELISA assay kits were used to determine the colonic levels of SOD, ROS, NF κB, and TLR 4. Results: Results: Macroscopic and microscopic assessments revealed that juglone significantly decreased colonic tissue damage and inflammation at 150 mg/kg. Juglone at 100, 150 mg/kg significantly decreased the TNF-α, MPO, and TLR-4 levels, as well as the SOD activity. All juglone-treated groups reduced the NF-κB levels compared to the control group (p < 0.001). The compound decreased the IL-1β, and ROS levels at the concentration of 150 mg/kg. Juglone attenuated colitis symptoms, reduced inflammation cytokines, declined neutrophil infiltration, and suppressed IL- 1β and TNF-α expressions in acetic acid-induced colitis rats. It may be proposed that juglone improved colitis in animal model through suppression of inflammatory parameters and downregulation of the NF-κB-TLR-4 pathway. Conclusion: Juglone exhibited anti inflammatory and antioxidant effects in the experimental colitis model and could be a therapeutic candidate for IBD. Juglone should be a subject for fur-ther animal and clinical trials in IBD models and for safety concerns.