Rumex japonicus Houtt. Extract Suppresses Colitis-Associated Colorectal Cancer by Regulating Inflammation and Tight-Junction Integrity in Mice

Abstract

Irritable bowel disease (IBD), which results in an elevated risk of colitis-associated colorectal cancer (CAC), is characterized by inflammation and barrier disruption of the gut. The genus Rumex has anti-oxidative and anti-inflammatory effects, and the roots of Rumex japonicus Houtt (RJ) have been traditionally used in East Asia to treat digestive problems. We investigated the protective effect of RJ against azoxymethane (AOM)-and dextran sulfate sodium (DSS)-induced CAC in C57BL/6N male mice. The mice were intraperitoneally injected with AOM on the first day and orally treated with 2% DSS for 2 weeks (on the third and sixth weeks). RJ extract (100 mg/kg) was administered to the mice in the RJ group for 4 weeks (from the third to sixth week), and all mice were sacrificed on the final day of the eighth week. Changes in morphology, tight junctions (TJs), inflammation-related factors in the colon and serum inflammatory cytokine levels were measured. The colons of AOM/DSS-treated mice were shorter and heavier than those of normal mice. The number of tumors in the colons of AOM/DSS-treated mice increased; however, RJ suppressed these changes. RJ also reduced the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in the colon and serum, and it increased the level of IL-10 in the colon. Moreover, RJ inhibited the barrier disruption and apoptosis in the colons of AOM/DSS-treated mice. RJ effectively suppressed AOM/DSS-induced CAC by inhibiting tumor formation, inflammation, disruption of TJ, and apoptosis in the colon.

Laherradurin Inhibits Tumor Growth in an Azoxymethane/Dextran Sulfate Sodium Colorectal Cancer Model In Vivo

“…Similar results were observed for the reduction in tumor size, with the dose of 3.0 mg/Kg being more effective than cisplatin. Other works report that mice administered AOM/DSS show colon shortening, changes in morphology, and tissue stiffness [47,56,57], agreeing with our results since the groups with induced CRC showed a decrease in colon length compared with the group of healthy mice. The histopathology results obtained by hematoxylin-eosin staining suggest that those mice administered LH displayed restoration of the damaged mucosa layer, recovery of the lamina propria, and the absence of adenoma and intramucosal carcinoma.…”

“…Such results are similar to the effect caused by cisplatin. It is still not known how ACGs inhibit morphological changes in the tumor cell; however, the upregulation of pro-inflammatory cytokines can control tumor formation in the colon [57,58].…”

Selenium-containing soybean peptides ameliorate intestinal inflammation and modulate gut microbiota dysbacteriosis in DSS-induced ulcerative colitis mice

“…37 However, IL-10 could protect the tight junction proteins. 38 The L-SePP treatment group showed no remarkable difference in the levels of TNF-α, IL-6 and IL-10, which were comparable with the normal levels ( P > 0.05). In contrast, H-SePPs could not alter the levels of inflammatory cytokines in DSS-induced colitis mice.…”

“…37 However, IL-10 could protect the tight junction proteins. 38 The L-SePP treatment group showed no remarkable difference in the levels of…”