Interleukin 6 inhibition by triptolide prevents inflammation in a mouse model of ulcerative colitis

Zhang, Haifeng; Chen, Weichang

doi:10.3892/etm.2017.4778

Cited by 21 publications

(18 citation statements)

References 31 publications

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“…Pharmacological and clinical tests have demonstrated its immunosuppressive, antiinflammatory, and other biological activities (Banerjee et al, 2013;Lin et al, 2001;Wu et al, 2013;Zheng et al, 2013). Triptolide exerts positive effects on UC (Wei et al, 2008;Zhang and Chen, 2017). Here, we used a DSS-induced UC mouse model and recorded general signs, DAI, and colon length, thickness, lesion gross score, and histopathology score along with the analysis of serum levels of TNF-a, IL-6, and IL-17.…”

Section: Discussionmentioning

confidence: 99%

“…It exerts anti-inflammatory, immunosuppressive, and antitumor activities and has been widely used for the treatment of various inflammatory diseases (Lin et al, 2001;Lee et al, 2012;Wu et al, 2013;Zheng et al, 2013;Banerjee et al, 2013). Recent studies have shown that triptolide exerts beneficial effects against UC (Wei et al, 2008;Zhang et al, 2016;Zhang and Chen, 2017). Triptolide is also closely related to the gut microbiota through its immunosuppressive effects (Goldszmid and Trinchieri, 2012;Furusawa et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice

Rao

et al. 2020

Front. Pharmacol.

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Triptolide is beneficial for the treatment of ulcerative colitis (UC), which is closely related to the gut microbiota. However, whether the therapeutic effects of triptolide involve the regulation of the gut microbiota is still unclear. In the present study, animal models of UC mice induced by dextran sodium sulfate (DSS) were established, the changes of gut microbiota in mice were detected by high-throughput sequencing. The effects of triptolide on DSS-induced UC mouse and its gut microbiota were studied. As a result, we found that triptolide exerted anti-inflammatory and therapeutic effects on UC mice. Sequencing results for the gut microbiota showed that the composition of the gut microbiota from DSS group was disordered as compared with that from the control group, consistent with a decrease in the abundance of flora. Triptolide treatment accelerated the recovery of the population of the gut microbiota and significantly improved the microbial diversity. At the phylum level, the population of Bacteroidetes decreased and that of Firmicutes increased. At the genus level, Bacteroides and Lachnospiraceae counts decreased. Thus, triptolide could regulate the composition of the gut microbiota, accelerate the recovery of microbiota, and exert good therapeutic effects in UC mice. Our results also revealed that fecal transplantation from triptolide-treated mice could relieve UC. This study provides a reference for the rational use of triptolide for the treatment of UC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice

Rao

et al. 2020

Front. Pharmacol.

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“…40 IL-6 is an interleukin that acts as both a proinflammatory cytokine and an anti-inflammatory cytokine. 41 It is secreted by T cells and macrophages that can stimulate the immune response, thus causing inflammation if overexpressed. NO is a signaling molecule that plays a key role in the pathogenesis of inflammation.…”

Section: Intestinal Permeabilitymentioning

confidence: 99%

Galactosylated PLGA nanoparticles for the oral delivery of resveratrol: enhanced bioavailability and in vitro anti-inflammatory activity

Siu

Lin

et al. 2018

IJN

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BackgroundResveratrol (RES) is a natural anti-inflammatory and antioxidant compound with poor water solubility and oral bioavailability. The present study takes the advantages of nanocarriers combined with a ligand (galactose) anchoring to orally deliver RES in an attempt to improve its bioavailability and pharmacological activity.MethodsRES-loaded galactosylated nanoparticles (RES-GNPs) were prepared by solvent diffusion technique using poly(lactic-co-glycolic acid), synthesized N-oleoyl-d-galactosamine and Tween 80. RES-GNPs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Oral bioavailability and in vitro anti-inflammatory activity were investigated in rats and lipopolysaccharides-induced RAW 264.7 cells, respectively.ResultsThe resulting RES-GNPs were 108.4 nm around in particle size with a polydispersity index of 0.217. Furthermore, RES-GNPs possessed a high EE and a slow drug release in water. After oral administration, RES-GNPs significantly enhanced the oral bioavailability of RES, up to 335.7% relative to RES suspensions. In situ single-pass intestinal perfusion and cellular uptake experiments showed that GNPs could improve the intestinal permeability and transcellular transport of RES. Moreover, the anti-inflammatory efficacy of RES-GNPs in RAW 264.7 cells model was superior to free RES and RES-GNPs.ConclusionThe results indicate that RES-GNPs can effectively promote the intestinal absorption of RES and strengthen its bioactivity, which may be a promising system for the treatment of inflammatory diseases.

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“…TrkB-PLC/IP3 pathway is mainly consisted of protein-tyrosine kinase receptor B (TrkB), phospholipase C (PLC) and inositol triphosphate (IP3). After the specific binding of brain-derived neurotrophic factor (BDNF) to TrkB, TrkB is phosphorylated to p-TrkB, which activates the signal transduction of PLC/IP3 in the downstream, thereby playing roles in the increase of intracellular Ca 2+ concentration, the enhancement of nerve-muscle excitation conduction, the promotion of cell mobility in the intestinal smooth muscle, and the promotion of intestinal motility [14][15][16][17][18][19]. At present, there is no research showing the regulatory mechanism of TrkB-PLC/IP3 pathway on colitis.…”

Section: Introductionmentioning

confidence: 99%

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

Sun

et al. 2020

Preprint

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Background This study aimed to explore the effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis.Methods Forty 8-week SPF C57BL/6J mice were randomly and averagely divided into normal group (healthy mice), control group (sham-operated mice), model group (model mice without any treatment), and K252a group (model mice with the treatment of 100 μmoL/kg TrkB-PLC/IP3 pathway inhibitor for 5 d before clysis). Mice in model and K252a groups were used to establish ulcerative colitis models after medication.Results There were no significant changes of the content of serum tumor necrosis factor-α (TNF-α) and TNF-γ and protein expressions of TNF-α and TNF-γ in the colon tissues (all P >0.05), a significant increase of disease activity index, colon mucosa damage index, tissue damage index scores, content and protein expressions of serum interleukin-4 (IL-4) and IL-8, and a significant decrease of content and protein expressions of serum IL-10 (all P <0.05) in model and K252a groups, as compared to normal and control groups. Mice in model and K252a groups had blocked enterocyte cycle progression, raised apoptosis ratio, significantly increased mRNA and protein expressions of Caspase3, Bax, FasL and Fas, and significantly reduced mRNA and protein expressions of p-TrkB, PLC-γ1, IP3 and Bcl-2 (all P <0.05). Moreover, intestinal inflammation and apoptosis induced by colitis in K252a group became more aggravated through the inhibition of TrkB-PLC/IP3 pathway activity.Conclusions Inhibition of TrkB-PLC/IP3 pathway can promote the expression of intestinal inflammatory factors and enterocyte apoptosis in mice with colitis.

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Interleukin 6 inhibition by triptolide prevents inflammation in a mouse model of ulcerative colitis

Cited by 21 publications

References 31 publications

Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice

Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice

Galactosylated PLGA nanoparticles for the oral delivery of resveratrol: enhanced bioavailability and in vitro anti-inflammatory activity

Effect of TrkB-PLC/IP3 pathway on intestinal inflammatory factors and enterocyte apoptosis in mice with colitis

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