Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways

Abstract

To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg d) and DSS + high-βGs (1000 mg kg d). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…It is reported that Lentinus edodes β-glucans (500 and 1000 mg/kg) treatment can increase the body weight, improve DAI and modify p38MAPK and ERK1/2 in DSSinduced UC mice, and then phosphorylate PPARγ, which negatively regulates activation of NF-κB [124].…”

“…Attenuate the expression of proteins in the NF-κB [122] Oligonol DSS-induced colon tissue Decrease nuclear translocation of NF-κBp65 [123] Lentinus edodes β-glucans RAW264.7 cells Inhibit NF-κB activation [124] Mango extract CCD-18Co cells Reduce expression of NF-κB and pNF-κB protein [125] Astringent medicine Muscovite Iodoacetamide-induced colitis tissues…”

“…Reverse the increased expression of IKKα and p-IκB [118] The fruit of Ziziphus jujuba Mill. AOM/DSS-induced colon tissue Attenuate inflammation, tumor development and progression by down-regulation of expression of STAT3 [122] Lentinus edodes β-glucans DSS-induced colon tissues Modify p38MAPK and ERK1/2, and then phosphorylating PPARγ, which negatively regulates activation of NF-κB [124] Mango polyphenolics…”

Lipid Oxidation Products in the Pathogenesis of Inflammation-related Gut Diseases

“…The bioactive derivative of acrolein, cinnamaldehyde, is indeed known for its antiproliferative and pro-apoptotic effects, and is now considered as having anticancer properties consisting in modulating cell signaling pathways: for instance, it inhibits survival PI3K/Akt signaling in a number of CRC cells [28] and activates cytoprotective antioxidant response in human epithelial colon cells by inducing Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2) [29]. Increased MDA tissue levels have been detected in inflamed colonic tissues induced in rodents [30][31][32][33], by the administration of dextran sodium sulfate (DSS) in mice, or trinitrobenzene sulfonic acid (TNBS) in rats. These two chemicals are commonly employed in inducing experimental colitis [34,35].…”

MAP kinase phosphatase MKP-1 regulates p-ERK1/2 signaling pathway with fluoride treatment

“…Elk-1, after phosphorylation by ERK, binds to the SRE cis-acting element in the promoter region of c-fos and induces its transcription. Transcription factor Elk-1 is a part of the ternary complex which can be combined with serum effect factors (SRE) to regulate gene activity in order to reply to the serum and growth factors [16]. The activation of ERKl/2 is transferred from the cytoplasmic to nuclear and activates its downstream substrate EIk-1, and the phosphorylation of EIk-1 will promote the function of cell differentiation, proliferation and apoptosis [17][18][19].…”