Magnolol, a Natural Polyphenol, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice

Abstract

Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS)-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg) daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO) activity. Moreover, colonic pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) induced by colitis were dramatically decreased by magnolol. To further unveil the metabolic signatures upon magnolol treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in mice serum were performed. Compared with controls, abnormality of serum metabolic phenotypes in DSS-treated mice were effectively reversed by different doses of magnolol. In particular, magnolol treatment effectively elevated the serum levels of tryptophan metabolites including kynurenic acid (KA), 5-hydroxyindoleacetic acid, indoleacetic acid (IAA), indolelactic acid and indoxylsulfuric acid, which are potential aryl hydrocarbon receptor (AHR) ligands to impact colitis. These findings suggest that magnolol exerts anti-inflammatory effect on DSS-induced colitis and its underlying mechanisms are associated with the restoring of tryptophan metabolites that inhibit the colonic inflammation.

Host–microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling

“…62 In addition to serotonin itself, its catabolites, such as 5-HIAA, are potential AhR ligands. 63 Melatonin has been reported to modulate a number of physiological functions, notably circadian rhythm, free radical scavenging, and oxidation resistance. 64 However, whether melatonin can directly act as an AhR ligand remains to be elucidated.…”

Nitroso-oxidative stress after activation of 5-HT4 receptors under conditions of colitis in rats

“…These changes are quite obvious, as the increase of iNOS activity is mediated by the high content of inflammatory cytokines in the area of inflammation [36]. UC is characterized by destructive changes in CM, accompanied by increased content of MDA, protein and mRNA expressions of TNF-α [37], NF-κBp65 [38], IL-1β, IL-17 [39], IL-2, IL-4, IL-5 [40], increased activity of SOD and MPO [41], increased concentrations of prostaglandin E 2 and leukotriene B 4 , decreased total glutathione content [42], increased iNOS and COX-2 expression [43], as well as decreased activity of arginase due to bacterial lipopolysaccharides and flagellin admission, in addition to increased oxidative processes in the CM [44]. What is more, increased activity of iNOS under conditions of UC causes reduction of L-arginine concentration and arginase activity [45], indicating the redistribution of L-arginine utilization by NOS and arginase under conditions of inflammation.…”

Spexin Acts as Novel Regulator for Bile Acid Synthesis

“…The untargeted metabolic analysis was performed as described previously (Zhao et al, 2017 ). The four volumes of cold methanol containing 5 μg/mL of p-chlorophenylalanine solution as IS were added into 50 μL of serum for metabolites extraction and protein precipitation.…”