5‐Hydroxytryptamine (5‐HT)‐exacerbated DSS‐induced colitis is associated with elevated NADPH oxidase expression in the colon

Dong, Shizhen; Chen, Menglu; Dai, Faliang; Xuan, Qingxia; Chen, Pan; Feng, Dandan; Gao, Lei; Zhu, Chendi; Chang, Yongchao; Chu, Fong‐Fong; Gao, Qiang

doi:10.1002/jcb.28198

Cited by 22 publications

(24 citation statements)

References 48 publications

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“…For immunohistochemical (IHC) staining, mouse anti-rabbit F4/80 (GB11027, Servicebio, Hubei, China, 1:300 dilution) was used as the primary antibody, and goat anti-rabbit IgG was the secondary antibody (GB23303, Servicebio, Hubei, China, 1:200 dilution). IHC was performed using previously described protocols (Dong et al, 2019). Negative control sections were treated in the same manner, with omission of the primary antibody.…”

Section: Methodsmentioning

confidence: 99%

Safranal Alleviates Dextran Sulfate Sodium-Induced Colitis and Suppresses Macrophage-Mediated Inflammation

et al. 2019

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Introduction: Crocus sativus (saffron) is widely used in China, Iran, and India for dyeing and as a food additive and medicinal plant. Safranal, as one of the main constituents of saffron, is responsible for its aroma and has been reported to have anticancer, antioxidant, and anti-inflammation properties.Objective: In this study, we investigated the anti-inflammatory effects of Safranal in RAW264.7 cells, bone marrow-derived macrophages (BMDMs), and dextran sulfate sodium (DSS)-induced colitis mice.Methods: Safranal toxicity was determined using an MTT assay. We evaluated the inhibitory effect of nitric oxide (NO) and levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells and BMDMs. We assessed the inhibitory effect of pro-inflammatory cytokines, and the mRNA expressions of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), classical inflammatory pathways (MAPK and NF-κB), and the nuclear translocation factors AP-1 and NF-κB p65 were investigated. The in vivo anti-inflammatory effects of Safranal were assessed in a DSS-induced colitis model. DSS3.5% was used to induce colitis in mice with or without Safranal for 7 days; weight and disease activity index (DAI) were recorded daily. At the end of the experiment, the colon, mesenteric lymph nodes (MLNs), and spleen were collected for flow cytometry, ELISA, and Western blot analysis.Results: Safranal suppressed NO production, iNOS, and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BMDMs. Safranal decreased the production and mRNA expression of IL-6 and TNF-α in the RAW264.7 cell line and inhibited the phosphorylation and nuclear translocation of components of the MAPK and NF-κB pathways. Safranal alleviated clinical symptoms in the DSS-induced colitis model, and colon histology showed decreased severity of inflammation, depth of inflammatory involvement, and crypt damage. Immunohistochemical staining and flow cytometry showed reduced macrophage infiltration in colonic tissues and macrophage numbers in MLNs and the spleen. The levels of colonic IL-6 and TNF-α also decreased in Safranal-treated colitis mice. This study elucidates the anti-inflammation activity of Safranal, which may be a candidate for inflammatory bowel syndrome (IBD) therapy.

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Section: Methodsmentioning

confidence: 99%

Safranal Alleviates Dextran Sulfate Sodium-Induced Colitis and Suppresses Macrophage-Mediated Inflammation

et al. 2019

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“…[ 146 ] On the contrary, mice treated with 1% DSS or DSS + 5‐HT showed an exacerbation in colitis that further increased NOX expression in mice colons. [ 183 ] In the mouse model, spontaneous chronic colitis is associated with an increase in 5‐HT levels. [ 184 ] However, new clues suggest that 5‐HT modulate the intestinal microbiota composition by acting on 5‐HTRs exert pro/anti‐inflammation, [ 31,162,185 ] and upregulation of the pro‐inflammatory cytokines (IL‐6, TNF‐α, and IL‐8) through 5‐HT binding to its receptors, namely 5‐HTR3, 5‐HTR4, and 5‐HTR7 in DCs.…”

Section: Role Of Trp and Its Metabolites In Inflammatory Bowel Diseasementioning

confidence: 99%

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

Zhang

Zabed

et al. 2021

Molecular Nutrition Food Res

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Inflammatory bowel disease (IBD) is complex, chronic, and relapsing gastrointestinal inflammatory disorders, which includes mainly two conditions, namely ulcerative colitis (UC) and Crohn's disease (CD). Development of IBD in any individual is closely related to his/her autoimmune regulation, gene‐microbiota interactions, and dietary factors. Dietary tryptophan (Trp) is an essential amino acid for intestinal mucosal cells, and it is associated with the intestinal inflammation, epithelial barrier, and energy homeostasis of the host. According to recent studies, Trp and its three major metabolic pathways, namely kynurenine (KYN) pathway, indole pathway, and 5‐hydroxytryptamine (5‐HT) pathway, have vital roles in the regulation of intestinal inflammation by acting directly or indirectly on the pro/anti‐inflammatory cytokines, functions of various immune cells, as well as the intestinal microbial composition and homeostasis. In this review, recent advances in Trp‐ and its metabolites‐associated intestinal inflammation are summarized. It further discusses the complex mechanisms and interrelationships of the three major metabolic pathways of Trp in regulating inflammation, which could elucidate the value of dietary Trp to be used as a nutrient for IBD patients.

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“…DSSinduced colitis is associated with elevated NADPH oxidase expression in the colon. 30 Pro-inflammatory cytokines including TNF-α, IL-17 and IL-23 have been considered to play a central role in the processes of UC. 31 PGE2 was increased significantly in patients with IBD, which was important indicator for evaluating the degree of UC.…”

Section: Effect Of Dfnps On the Activity Of Nadph Oxidase And The Production Of Pro-inflammatory Cytokinementioning

confidence: 99%

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis

Gao¹,

Yu²,

Zhang³

et al. 2021

IJN

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Aim Iridoid glycosides (IG) as the major active fraction of Syringa oblata Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats. Materials and Methods We prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model. Results SEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of COX-2 and MMP-9 and the production of TNF-α, IL-17, IL-23 and PGE2. Conclusion We confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.

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5‐Hydroxytryptamine (5‐HT)‐exacerbated DSS‐induced colitis is associated with elevated NADPH oxidase expression in the colon

Cited by 22 publications

References 48 publications

Safranal Alleviates Dextran Sulfate Sodium-Induced Colitis and Suppresses Macrophage-Mediated Inflammation

Safranal Alleviates Dextran Sulfate Sodium-Induced Colitis and Suppresses Macrophage-Mediated Inflammation

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis

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