Inonotus obliquus Polysaccharide Ameliorates Azoxymethane/Dextran Sulfate Sodium-Induced Colitis-Associated Cancer in Mice via Activation of the NLRP3 Inflammasome

Abstract

Inonotus obliquus polysaccharide (IOP), the primary constituent of the parasitic fungus Inonotus obliquus, has anti-tumor, anti-inflammatory, anti-oxidation effects. However, the roles of IOP on colitis-associated cancer (CAC) are still unclear. Herein, we tested the efficacy of IOP using a mouse model of CAC induced by azoxymethane and dextran sulfate sodium (AOM/DSS). We confirmed that intragastric administration of IOP decreased CAC-induced body weight loss, colon tissue damage, colon shortening, and expression of proinflammatory mediators. Meanwhile, IOP treatment increased in expression of the NLRP3 inflammasome, IL-1β, and IL-18 in the colon of CAC mice. Moreover, in vitro, IOP inhibited the proliferation of SW620 colorectal cancer cells. Finally, overexpression of NLRP3 with plasmid transfection could further enhance the activation of NLRP3 inflammasome by IOP. Taken together, these results suggest that IOP suppresses the development of CAC, possibly by activation of the NLRP3 inflammasome, and reveal that IOP may be a therapeutic drug candidate for CAC.

Recent Developments in Inonotus obliquus (Chaga mushroom) Polysaccharides: Isolation, Structural Characteristics, Biological Activities and Application

“…Besides, Jiang’s research demonstrated that IOPS could significantly inhibit allograft tumor growth of the LLC1 cells with increased apoptosis at 50 mg/kg dosage [ 100 ]. Li tested the efficacy of IOPS by using a mouse model of Colitis-Associated Cancer (CAC) induced by azoxymethane and dextran sulfate sodium (AOM/DSS) to confirm that IOPS inhibited the proliferation of SW620 colorectal cancer cells [ 22 ].…”

“…When the activation of NLRP3 inflammasome is inhibited, the inflammation-related diseases involved in it may be improved. In Lipopolysaccharide (LPS)-induced macrophage inflammation, Zheng found that IOPS can inhibit the expression of IL-18 and IL-1β by inhibiting the phosphorylation of NF-κB-p65 ( p < 0.05) [ 22 , 138 , 139 ].…”

“…[ [18][19][20][21][22][23][24] Polyphenol Antioxidant [25] Triterpenoid Anticancer, anti-inflammatory, antiviral, and antioxidant [26][27][28][29][30] Melanin Antioxidant, anti-inflammatory, antiviral, hypolipidemic and immunomodulatory [24,[31][32][33][34] Polysaccharides are natural biopolymers that all living organisms have. And the diversity in monosaccharide composition and structure causes them to have different biological activities [35].…”

“…Over several decades, remarkable progress has been realized, and especially during the past decade, polysaccharides' anticancer, hypoglycemic, and antiviral effects were popular research topics. Among all the active components in Inonotus obliquus, Inonotus obliquus polysaccharides have the broadest biological activity, such as anticancer, hypoglycemic, antiinflammatory, and anti-oxidation effects [8,22,. Through the number of Scopusindexed publication numbers (archived until 15 March 2021) for polysaccharide bioactivity, Inonotus obliquus, Inonotus obliquus polysaccharide related articles, a certain degree of upward trend can be seen (Figure 1), which means that the medicinal value and health value of Inonotus obliquus have been widely recognized and affirmed [5,6,[62][63][64], making it worthwhile to review Inonotus obliquus polysaccharides.…”

“…Among all the active components in Inonotus obliquus , Inonotus obliquus polysaccharides have the broadest biological activity, such as anticancer, hypoglycemic, anti-inflammatory, and anti-oxidation effects [ 8 , 22 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Through the number of Scopus-indexed publication numbers (archived until 15 March 2021) for polysaccharide bioactivity, Inonotus obliquus , Inonotus obliquus polysaccharide related articles, a certain degree of upward trend can be seen ( Figure 1 ), which means that the medicinal value and health value of Inonotus obliquus have been widely recognized and affirmed [ 5 , 6 , 62 , 63 , 64 ], making it worthwhile to review Inonotus obliquus polysaccharides.…”