Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora

Abstract

Background: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. Methods: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model. Results: IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion. Conclusions: Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions).

Gut Microbiota, Short-Chain Fatty Acids, and Herbal Medicines

“…Indigo naturalis (Qing dai) is an ancient herbal medicine that has been used as an anti-inflammatory agent to treat skin rash, dermatitis, upper airway inflammation etc. Adachi et al found out that Indigo naturalis could significantly aggravate colitis induced by oxazolone, and this process is associated with modulation of gut microbiota (Adachi et al, 2017 ). Ganoderma lucidum is traditionally used for promoting health and longevity, but a recent study found out that Ganoderma lucidum also has detrimental effects.…”

Role of eosinophils in a murine model of inflammatory bowel disease

“…The colonoscopic findings were scored based on mucosal granularity (0, none; 1, mild; 2, moderate; and 3 severe), visibility of vascular pattern (0, normal; 1, mildly decreased; 2, moderately decreased; and 3, severely decreased), erosion or ulceration (0, normal; 1, erythema; 2, erosion; and 3, ulcer), and stool consistency (0, normal; 1, soft; 2, muddy; and 3, watery) [21,22].…”

“…Sections were scored on a scale of 0-3 (0, none; 1, mild; 2, moderate; 3, severe) for epithelial hyperplasia, enterocyte loss, crypt inflammation, mononuclear infiltrate, and polymorphonuclear infiltrate. The histopathology score is the summation of scores from all these criteria [22].…”

Recent Advances in Experimental Allergy

“…Jin et al [37] used an HDM-induced AD mouse model, in which DFE is used to induce AD on exposed skin of mouse ears by repeated applications, to investigate the anti-allergic effects of 1,2,4,5-tetramethoxybenzene (TMB). TMB can be isolated from the plant extract of the Amomum xanthioides species [38, 39].…”

“…Furthermore, the authors proposed the mitogen-activated protein kinase (MAPK)-mediated mechanism for this observation. The in vitro results further highlight the potential of TMB as a therapeutic agent in AD [37]. …”