Colchicine increases intestinal permeability, suppresses inflammatory responses, and alters gut microbiota in mice

Shi, Yu; Li, Jiande; Yang, Pengfei; Niu, Zhanyu; Li, Wei; Chen, Linchi; Gao, Lan

doi:10.1016/j.toxlet.2020.09.018

Cited by 36 publications

(51 citation statements)

References 61 publications

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“…The integrity of intestinal epithelium is considered to be the rst defense line of the gastrointestinal tract [26]. Studies have shown that HFD lead to damaged intestinal epithelial barrier by increasing in ammation [27]. In this study, H&E staining results demonstrated that the vacuoles of lipid accumulation in colonic villi from HFD mice were increased, and ARPs signi cantly improved these phenomenons (Fig.…”

Section: Arps Attenuated Hfd-induced Colon In Ammationsupporting

confidence: 54%

“…In this study, the expression of tight-junction proteins in the colon epithelium was reduced in mice on HFD, ARPs supplementation protected against this effect. Impaired intestinal barrier integrity impelled LPS and intestinal in ammatory factors to enter the circulation, and trigger or exacerbate systemic in ammation [26,27]. In this study, increased LPS and TNF-α concentrations induced by HFD was abolished by ARPs.…”

Section: Discussionmentioning

confidence: 60%

“…HFD has been reported to induce intestinal microbial disorder and increase LPS production, which lead to increased LPS and in ammatory factors levels in the circulatory system, causing or aggravating systemic in ammation [27]. In this study, the contents of serum LPS and TNF-α in mice on HFD were signi cantly increased, and ARPs could effectively ameliorate the phenomenon (Fig.…”

Section: Arps Attenuated Hfd-induced Colon In Ammationmentioning

confidence: 58%

“…Huang et al reported that probiotic supplements are potential novel agents for the treatment of age-related diseases [28]. They found that Bacteroides paracasei can modulate age-related cognitive decline by altering communication in the gut-brain axis [27]. A review by Chang et al reported that the conversion of L-glutamate to D-glutamate by Bacteroides and other bacterial species may affect cognitive function in Alzheimer's disease, which supports the importance of intestinal bacteria metabolism on cognitive function and memory [37].…”

Section: Discussionmentioning

confidence: 99%

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Dietary Supplement of Anoectochilus Roxburghii Polysaccharides Ameliorates Cognitive Dysfunction Induced by High Fat Diet via “Gut-Brain” Axis

Zhu

Tian

et al. 2021

Preprint

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Background：Anoectochilus roxburghii, a traditional Chinese herbal medicine, has been widely used for treating numerous metabolic diseases. Anoectochilus roxburghii polysaccharide (ARPs) is an important constituent of Anoectochilus roxburghii. This study tried to investigate whether ARPs could improve cognitive dysfunction in diet-induced obesity.Methods: C57BL/6J male mice were randomly divided into the normal chow diet group (CD), the high-fat diet group (HFD) and HFD supplemented with ARPs (HARPs). Morris water maze test and Y maze test were used to evaluate spatial learning and memory. Serum TNF-α and LPS concentrations were detected by ELISA. Genes involved in Neurotrophic factors, inflammation and Intestinal permeability were detected by RT-PCR. Immunohistochemistry was used to detect TNF-α and ZO-1 proteins. BDNF in hippocampus was detected by immunofluorescence staining. 16S rDNA sequencing was used to detect intestinal microbial diversity.Results: Dietary supplement of ARPs ameliorates cognitive dysfunction induced by HFD. Compared with HFD mice, body weight, plasma glucose, total cholesterol and triglyceride levels in HARPs group were decreased significantly. Moreover, the cognitive function and memory of HFD mice were decreased, while ARPs abolished these effects. In addition, Tau protein levels were decreased and BDNF increased significantly in hippocampus from HARPs mice. Furthermore, compared with HFD group, IL-6 and TNF-α levels in hippocampus and colon from HARPs mice were decreased. Moreover, ARPs increased the tight junction protein levels and intestinal microbiota diversity significantly.Conclusions: Diet supplemented with ARPs prevented mice from HFD-induced cognitive dysfunction, indicated that ARPs has a good effect on obesity-related neuropathy. Mechanically, these effects at least in part attribute to the “gut-brain” axis regulation, and which can provide reference for the development of ARPs as functional foods in the future.

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Section: Arps Attenuated Hfd-induced Colon In Ammationsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 60%

Section: Arps Attenuated Hfd-induced Colon In Ammationmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Dietary Supplement of Anoectochilus Roxburghii Polysaccharides Ameliorates Cognitive Dysfunction Induced by High Fat Diet via “Gut-Brain” Axis

Zhu

Tian

et al. 2021

Preprint

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“…Previous studies showed that colchicine applied to the proximal part of the injury site relieved the mechanical sensitivity, and the mechanically sensitive afferents exhibited impulse conduction blocks at the colchicine-treated site (Proske and Luff 1998). And colchicine can inhibit the levels of pro-in ammatory cytokines, such as IL-1β, IL-6, and TNF-α (Shi et al 2020). Based on these data, we speculated that the excellent analgesic effect of colchicine was due to blocking the conduction of electrical signals and reducing the levels of in ammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A relieve neuropathic pain by suppressing the expression of CXCL13/CXCR5 and GAT-1 in chronic constriction injury rats

Bu¹,

Jiao²,

Fan³

et al. 2021

Preprint

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Botulinum toxin type A (BTX-A) was widely used to treat neuropathic pain in clinic. The underlying analgesic mechanism of BTX-A involves in axonal transport. The chemokine (C-X-C motif) ligand 13 (CXCL13) and GABA transporter 1 (GAT-1) played important roles in chronic pain. We established a chronic constriction injury (CCI) model. The pain behaviors of rats were measured by testing paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs). The level of proteins was measured by western blots. In our results, the CCI rats showed decrease of PWTs and PWLs, which were relieved by BTX-A. BTX-A reversed the over-expression of CXCL13 and GAT-1 in spinal cord, DRG, sciatic nerve and plantar in CCI rats and characterized in dose-dependent manner. The inhibition of BTX-A on proteins we examined didn’t show significant trend among time points. The analgesic effect of BTX-A disappeared after the axon transport of sciatic nerve blocked by the colchicine. But the PWTs of the colchicine treated CCI rats were higher than non- colchicine-treated CCI rats. Colchicine decreased the levels of CXCL13 and GAT-1 in CCI rats. What’s more, the proteins we examined peaked at the sciatic nerve in the non-colchicine group, but the phenomenon disappeared in the colchicine group. In conclusion, the BTX-A and colchicine relieve neuropathic pain and suppress the increase of CXCL13 and GAT-1. Colchicine prevents the analgesic effect of BTX-A by blocking axon transport. The axon transport may play roles in the peripheral mechanisms of neuropathic pain.

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Colchicine disrupts bile acid metabolic homeostasis by affecting the enterohepatic circulation in mice

Shi,

Wei,

Jin

et al. 2024

J of Applied Toxicology

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Although the medicinal properties of colchicine (COL) have been widely known for centuries, its toxicity has been the subject of controversy. The narrow therapeutic window causes COL to induce gastrointestinal adverse effects even when taken at recommended doses, mainly manifested as nausea, vomiting, and diarrhea. However, the mechanism of COL‐induced gastrointestinal toxic reactions remains obscure. In the present study, the mice were dosed with COL (2.5 mg/kg b.w./day) for a week to explore the effect of COL on bile acid metabolism and the mechanism of COL‐induced diarrhea. The results showed that COL treatment affected liver biochemistry in mice, resulting in a significant down‐regulation of the mRNA expression levels of bile acid biosynthesis regulators Cyp7a1, Cyp8b1, Cyp7b1, and Cyp27a1 in liver tissues. The mRNA expression levels of bile acid transporters Ntcp, Oatp1, Mrp2, Ibabp, Mrp3, Osta, and Ostb in liver and ileum tissues were also significantly down‐regulated. In addition, COL treatment significantly inhibited the mRNA expression levels of Fxr and its downstream target genes Shp, Lrh1, and Fgf15 in liver and ileum tissues, affecting the feedback regulation of bile acid biosynthesis. More importantly, the inhibition of COL on bile acid transporters in ileal and hepatic tissues affected bile acid recycling in the ileum as well as their reuptake in the liver, leading to a significantly increased accumulation of bile acids in the colon, which may be an important cause of diarrhea. In conclusion, our study revealed that COL treatment affected bile acid biosynthesis and enterohepatic circulation, thereby disrupting bile acid metabolic homeostasis in mice.

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Colchicine increases intestinal permeability, suppresses inflammatory responses, and alters gut microbiota in mice

Cited by 36 publications

References 61 publications

Dietary Supplement of Anoectochilus Roxburghii Polysaccharides Ameliorates Cognitive Dysfunction Induced by High Fat Diet via “Gut-Brain” Axis

Dietary Supplement of Anoectochilus Roxburghii Polysaccharides Ameliorates Cognitive Dysfunction Induced by High Fat Diet via “Gut-Brain” Axis

Botulinum toxin type A relieve neuropathic pain by suppressing the expression of CXCL13/CXCR5 and GAT-1 in chronic constriction injury rats

Colchicine disrupts bile acid metabolic homeostasis by affecting the enterohepatic circulation in mice

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