Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model

Abstract

Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated-Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-κB (NFκB) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NFκB and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NFκB/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC.

Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways

“…In colitis rats, the observed up-regulation of pro-inflammatory cytokines including IL-6 was ameliorated by CP, meanwhile, phosphorylation of Stat3 and JAK2 was blocked. The results provided further evidences of the effects of CP on suppression of colitis and indicated the key role of IL-6/JAK2/STAT3 pathway as relevant targets of CP ( Huo et al, 2016 ).…”

Comparative Study on the Chemical Components and Gastrointestinal Function on Rats of the Raw Product and Licorice-Simmered Product of Polygala tenuifolia

“…Licorice is a common detoxifying Chinese medicine that achieves effects such as tonification of the spleen and Qi, heat clearance and detoxification, and pain relief [ 33 ]. The active ingredients in licorice, flavonoids, possess anti-inflammatory, antioxidative, antitumoral, and analgesic effects [ 34 ]. Licorice flavonoids can effectively inhibit gastric mucosal injury, promote gastric juice secretion, increase GAS levels and pepsin activity to enhance gastric mucosal defense, inhibit inflammatory factor release, and reduce mucosal inflammation [ 35 – 37 ].…”

Apoptosis Exerts a Vital Role in the Treatment of Colitis-Associated Cancer by Herbal Medicine

“…As well as the signaling pathways mentioned above, the NF-k B/JAK2/STAT3 signaling pathway was focused on in another study examining whether flavonoids extracted from Licorice prevented CAC development. Licorice flavonoids (0-100 mg/kg for 10 weeks) did affect apoptotic targets (Bax and Bcl-Xl), proliferationassociated targets (proliferating cell nuclear antigen (PCNA), p53, p21, and cyclinD1), and inflammation-associated targets (p-JAK2, p-STAT3, IKKa/b, and p-IkBa), showing considerable potential value of clinical use against CAC (Huo et al, 2016). In another CAC mouse model established by a foodborne carcinogen (2-Amino-1-methyl-6phenylimidazol [4, 5-b] pyridine [PhIP]) plus DSS, Trierpene extract isolated from Mushroom Ganoderma lucidum (GLT) exerted significant ameliorative effect.…”

“…Pure resveratrol was first isolated from the roots of white hellebore (Veratrum grandiflorum O. Loes) in 1940, and it has also been found to exist in the roots of Rheum rhaponticum L. (Huang et al, 2019). The active ingredient in licorice, which plays an anti-CAC role, is another polyphenol (Huo et al, 2016). In addition, Artemisia princeps Pampanini cv.…”