Anti-inflammatory effect of miltirone on inflammatory bowel disease via TLR4/NF-κB/IQGAP2 signaling pathway

Wang, Hongjian; Gu, Junfei; Hou, Xuefeng; Chen, Juan; Yang, Nan; Liu, Ying; Wang, Gang; Du, Mei; Qiu, Huihui; Luo, Yi; Jiang, Ziyu; Feng, Liang

doi:10.1016/j.biopha.2016.11.061

Cited by 41 publications

(30 citation statements)

References 21 publications

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“…Inflammatory cells and the secretion of related inflammatory mediators play critical roles in the development and progression of UC [ 25 ]. NF-κB, a key factor in the immune system, regulates the expression of several proinflammatory factors, such as TNF-α, IL-4, IL-6, COX-2, adhesion molecule-1 and chemokines.…”

Section: Discussionmentioning

confidence: 99%

Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway

Yang

Shen

et al. 2017

J Inflamm

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BackgroundHyperoside (Hyp) is a flavonoid glycoside compound that has been demonstrated to have anti-inflammatory, anti-apoptotic and antioxidant effects. However, the impact of Hyp on inflammatory bowel disease (IBD) has not been previously explored. Thus, we evaluated the role of Hyp in dextran sodium sulfate (DSS)-induced acute colitis in mice.MethodsWe established a mouse model of experimental acute colitis by treating mice with drinking water supplemented with 3.0% DSS for 7 days. The disease activity index (DAI), colon length, histological features and colonic malondialdehyde (MDA) levels were examined using appropriate methods, and COX-2 expression was examined by immunohistochemistry. TNF-α, IL-4, IL-6, IL-10, NF-κB p65, Bcl-2, Bax, Caspase-3, nuclear factor-erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1) and superoxide dismutase (SOD) levels in colorectal tissues were detected by RT-PCR and western blotting.ResultsHyp significantly attenuated DSS-induced changes in the DAI as well as DSS-induced colonic shortening and histological changes. Hyp also inhibited inflammation, a change reflected by decreases in TNF-α, IL-6, COX-2 and NF-κB p65 expression and increases in IL-10 expression. Hyp suppressed increases in the levels of apoptosis-related proteins, such as Caspase-3 and Bax, but upregulated the level of the anti-apoptotic protein Bcl2. In addition, Hyp also exerted antioxidant effects. The MDA content was decreased, and the expression of Nrf2 and its downstream targets HO-1 and SOD were increased by Hyp.ConclusionsBased on these findings, Hyp possesses the ability to attenuate colitis, possibly by mitigating colonic inflammation and apoptosis via activation of the Nrf2 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway

Yang

Shen

et al. 2017

J Inflamm

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“…70 As key pro-inflammatory mediators, TNF-α, IL-8, IL-1β, and IL-6 cause intestinal mucosal impairment resulting in inflammation. 70,71 Elevated levels of the pro-inflammatory cytokines, such as IL-1β and TNF-α, are present in the gut mucosa of patients suffering from UC. The cytokines TNF-α and IL-1β have been intimately related to the stimulation of the production of IL-8 during the pathogenesis of UC.…”

Section: Figurementioning

confidence: 99%

“…83 TLR4/NF-κB pathway has been found to be closely related to the immune system and anti-inflammatory signaling pathways, in recent years. 71 The MyD88-dependent TLR4 signaling pathway is one of major signaling pathways in stimulating the production of NF-κB by activating TRAF6. 33 As a member of the toll-like receptors (TLRs) family, TLR4 can mediate the transport of signal factors across the plasma membrane.…”

Section: Figurementioning

confidence: 99%

Self-nanoemulsfiying drug delivery system of bruceine D: a new approach for anti-ulcerative colitis

Dou¹,

Zhou²,

Wang³

et al. 2018

IJN

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BackgroundBruceine D (BD) is a major bioactive component isolated from the traditional Chinese medicinal plant Brucea javanica which has been widely utilized to treat dysentery (also known as ulcerative colitis [UC]).MethodsTo improve the water solubility and absolute bioavailability of BD, we developed a self-nanoemulsifying drug delivery system (SNEDDS) composing of MCT (oil), Solutol HS-15 (surfactant), propylene glycol (co-surfactant) and BD. The physicochemical properties and pharmacokinetics of BD-SNEDDS were characterized, and its anti-UC activity and potential mechanism were evaluated in TNBS-induced UC rat model.ResultsThe prepared nanoemulsion has multiple beneficial aspects including small mean droplet size, low polydispersity index (PDI), high zeta potential (ZP) and excellent stability. Transmission electron microscopy showed that nanoemulsion droplets contained uniform shape and size of globules. Pharmacokinetic studies demonstrated that BD-SNEDDS exhibited enhanced pharmacokinetic parameters as compared with BD-suspension. Moreover, BD-SNEDDS significantly restored the colon length and body weight, reduced disease activity index (DAI) and colon pathology, decreased histological scores, diminished oxidative stress, and suppressed TLR4, MyD88, TRAF6, NF-κB p65 protein expressions in TNBS-induced UC rat model.ConclusionThese results demonstrated that BD-SNEDDS exhibited highly improved oral bioavailability and advanced anti-UC efficacy. In conclusion, our current results provided a foundation for further research of BD-SNEDDS as a potential complementary therapeutic agent for UC treatment.

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“…Current therapies for against IBD are limited by high costs, high toxicities and undesirable side effects (de Souza Ara ujo et al 2016;Wang et al 2017). This emphasizes the need to search for novel therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

Effect of riboflavin-producing bacteria against chemically induced colitis in mice

et al. 2017

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Aim: To assess the anti-inflammatory effect associated with individual probiotic suspensions of riboflavin-producing lactic acid bacteria (LAB) in a colitis murine model. Methods and Results: Mice intrarectally inoculated with trinitrobenzene sulfonic acid (TNBS) were orally administered with individual suspensions of riboflavin-producing strains: Lactobacillus (Lact.) plantarum CRL2130, Lact. paracasei CRL76, Lact. bulgaricus CRL871 and Streptococcus thermophilus CRL803; and a nonriboflavin-producing strain or commercial riboflavin. The extent of colonic damage and inflammation and microbial translocation to liver were evaluated. iNOs enzyme was analysed in the intestinal tissues and cytokine concentrations in the intestinal fluids. Animals given either one of the four riboflavin-producing strains showed lower macroscopic and histologic damage scores, lower microbial translocation to liver, significant decreases of iNOs+ cells in their large intestines and decreased proinflammatory cytokines, compared with mice without treatment. The administration of pure riboflavin showed similar benefits. Lact. paracasei CRL76 accompanied its antiinflammatory effect with increased IL-10 levels demonstrating other beneficial properties in addition to the vitamin production. Conclusion: Administration of riboflavin-producing strains prevented the intestinal damage induced by TNBS in mice. Significance and Impact of the Study: Riboflavin-producing phenotype in LAB represents a potent tool to select them for preventing/treating IBD.

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Anti-inflammatory effect of miltirone on inflammatory bowel disease via TLR4/NF-κB/IQGAP2 signaling pathway

Cited by 41 publications

References 21 publications

Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway

Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway

Self-nanoemulsfiying drug delivery system of bruceine D: a new approach for anti-ulcerative colitis

Effect of riboflavin-producing bacteria against chemically induced colitis in mice

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