Protection against ulcerative colitis and colorectal cancer by evodiamine via anti‑inflammatory effects

Abstract

evodiamine (evo) is an alkaloid that can be extracted from the berry fruit Evodia rutaecarpa and has been reported to exert various pharmacological effects, such as antidiarrheal, antiemetic and antiulcer effects. In vivo, the potential effects of evo were investigated in a mouse model of dextran sodium sulfate (dSS)-induced ulcerative colitis (uc) and in adenomatous polyposis coli (apc) Minc /Gpt c57Bl/6 mice with colorectal cancer (crc), where the latter harbours a point-mutation in the Apc gene. evo suppressed the degree of weight loss and colon shortening induced by dSS, decreased the disease activity index value and ameliorated the pathological alterations in the colon of mice with uc as examined via H&e staining of colon tissues. in addition, evo decreased the number and size of colonic tumors in apc Minc /Gpt mice. Proteomics (colon tissues), eliSa (colon tissues and serum) and western blotting (colon tissues) results revealed that evo inhibited nF-κB to mediate the levels of various cytokines, including, in the dSS-induced uc model, il-1β, il-2, il-6, il-8, TnF-α, iFn-γ (eliSa of colon tissues and serum), nF-κB, iKKα+β, iκBα, S100a9, Tlr4 and Myd88 (western blotting of colon tissues), and, in the colorectal cancer model, il-1β, il-2, il-6, il-15, il-17, il-22, TnF-α (eliSa of colon tissues and serum), nF-κB, iKKα+β, iκBα and S100a9 (western blotting of colon tissues), to achieve its anti-inflammatory and antitumor effects. In vitro, evo also reduced the viability of the colon cancer cell line SW480, inhibited mitochondrial membrane potential (MMP detection), caused G 2 /M-phase arrest (cell cycle detection) and suppressed the translocation of phosphorylated-nF-κB from the cytoplasm into the nucleus (immunofluorescence of p-NF-κB). Theoretical evidence (Md simulations) suggest that evo may bind to the ordered domain (α-helix) of nF-κB to influence this protein. The protein secondary structure changes were analyzed by the cpptraj module in amber. in addition, these data provide experimental evidence that evo may be an effective agent for treating uc and crc.

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

“…The paraffin-embedded samples were sectioned to 5 μ m thickness and stained with hematoxylin-eosin staining (H&E) for histological analysis. The detailed process was reported previously [ 46 ]. Representative images were measured under the microscope.…”

Oral administration of Lactobacillus paracasei N1115 on neonatal mice prevents the intestinal inflammation in adulthood

“…2022; Zhang et al . 2022), which were both shown in mRNA levels of colon tissue and the corresponding proteins expressed in serum, colon tissues, and its in vitro culture supernatant. Imbalanced production of cytokines profile is a part of the pathophysiology of intestinal inflammation, the products by T helper cells (Th1, Th2, and Th17) is complex that the increased TNF, IL‐6, IL‐17, and KC from a Th1‐Th17‐mediated acute inflammation played a dominant role in DSS colitis (Egger et al .…”

Synergistic Effect of Huangqin Decoction Combined Treatment With Radix Actinidiae chinensis on DSS and AOM-Induced Colorectal Cancer

“…Inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), has been suggested to be associated with the occurrence of CRC ( Zhang, 2020 ). CRC originates from inflamed mucosa and develop in the cascade of inflammation and cancer progression ( Terzić et al, 2010 ; Zhang, 2020 ). In this pathological transformation, chronic inflammation plays a crucial role.…”

“…The incidence and mortality rates of CRC are high in China, especially in Guangdong province ( China Anti-Cancer Association, 2022 ). Currently, inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD) is considered to be closely related to the occurrence and development of CRC ( Zhang, 2020 ).…”