β-Naphthoflavone Activation of the Ah Receptor Alleviates Irradiation-Induced Intestinal Injury in Mice

Zhou, Xiaoliang; Li, Deguan; Xu, Wenqing; Zhang, Heng; Wang, Hao; Perdew, Gary H.

doi:10.3390/antiox9121264

Cited by 9 publications

(3 citation statements)

References 41 publications

(19 reference statements)

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“…A recent study showed intraperitoneal administration of I3C reduced intestinal inflammation in a mouse model of TNBS-induced colitis via alterations in the gut microbiota [15]. Similarly, other dietary AhR ligands such as tryptophan and β-napthoflavone (BNF) have been shown to attenuate intestinal inflammation [16,17]. However, an in-depth analysis of how I3C through dietary consumption impacts ulcerative colitis as well as ileitis resembling CD has not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Potential Dietary and Therapeutic Strategies Involving Indole-3-Carbinole in Preclinical Models of Intestinal Inflammation

Qazi,

Comiskey,

Calzadilla

et al. 2023

Nutrients

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Diet–microbiota interactions are emerging as important contributors in the pathogenesis of inflammatory bowel diseases (IBD), characterized by chronic inflammation of the GI tract. The aryl hydrocarbon receptor (AhR) transcription factor regulates xenobiotic metabolism and is activated by exogenous ligands, including indole-3-carbinole (I3C), which is found in cruciferous vegetables. However, studies investigating the impact of dietary I3C and AhR in preclinical models resembling human IBD are lacking. Mice (WT or AhR KO in IECs, 6–8 weeks) or SAMP/YitFC and AKR/J control (4 weeks, m/f) were fed an AhR ligand-depleted or I3C (200 ppm)-supplemented diet. There were increased levels of LPS and exacerbated inflammation, resulting in increased mortality in AhRΔIEC mice fed the AhR ligand-depleted diet in response to chronic DSS. The mechanisms underlying the protective effects of I3C supplementation during colonic colitis involved amelioration of intestinal inflammation and restoration of the altered gut microbiota, particularly the families of clostridicae and lachnospriaceae. Furthermore, the AhR-depleted diet led to the emergence of pathobiont Parvibacter caecicola in WT mice. SAMP/YitFc mice with spontaneous ileitis showed significant recovery in epithelial abnormalities when fed dietary I3C. These data demonstrate the critical role of AhR and the mechanisms of dietary I3C in maintaining epithelial homeostasis and ameliorating inflammation.

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Section: Introductionmentioning

confidence: 99%

Potential Dietary and Therapeutic Strategies Involving Indole-3-Carbinole in Preclinical Models of Intestinal Inflammation

Qazi,

Comiskey,

Calzadilla

et al. 2023

Nutrients

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“…Recent studies also observed that PMF administration had impacts on gut microbiota in obesity and metabolic syndrome models [ 14 ]. Flavonoids, for example, β-naphthoflavone [ 15 ], were validated to protect cells from radiation-induced injury, yet the protective effects of PMFs on radiation-induced injury in vivo have not been fully discussed.…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Sour Orange (Citrus aurantium L.) Polymethoxyflavones on Mice Irradiation-Induced Intestinal Injury

Jiang

Wang

et al. 2022

Molecules

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Sour orange (Citrus aurantium L.) is one of the biological sources of polymethoxyflavones (PMFs), which are often used to deal with gastrointestinal diseases. The intestine is highly sensitive to irradiation damage. However, limited certain cures have been released for irradiation-induced gastrointestinal injury, and the potentials of sour orange PMFs as radio-resistance agents have not been fully discussed yet. The present study aims to (1) investigate the PMF components in 12 sour orange cultivars, (2) determine the protective effects of PMFs on irradiation-induced intestinal injury by treating mice that received 12 Gy abdominal irradiation with different doses of PMFs and observing the changes in organ indexes and pathological sections and (3) test cytotoxicity of PMFs by CCK-8 method. The results showed that sour orange PMFs appeared to have high intraspecies similarity. Besides, PMFs protected mice from irradiation-induced injury by alleviating body weight loss, reliving organ index changing and maintaining the intestinal structure. Finally, IC50 concentrations to cell line CCD 841 CoN of PMFs and nobiletin were calculated as 42.23 μg/mL and 51.58 μg/mL, respectively. Our study uncovered PMF contents in 12 sour orange materials and determined the protective effects on irradiation-induced intestinal injuries, providing guidance for the utilization of sour orange resources.

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“…RIII prevention and treatment research is mainly focused on natural antioxidants (such as vitamins and amino acids), known body protectors, newly synthesized compounds, and biotechnological methods. [7][8][9] A large number of studies have shown that Chinese medicines or extracts may alleviate radiation damage, [10][11][12][13][14] and also have protective effects on radiation enteritis, 15,16 including menthol and ginseng, which are attracting increasing attention due to their low toxicity and are used for radiation protection and treatment. 17,18 Therefore, Chinese medicine compounds may be effective in RIII protection and therapy.…”

Section: Introductionmentioning

confidence: 99%

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

Dong

Zhang

Wang

et al. 2022

Anim Models and Exp Med

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Background: Gastrointestinal (GI) injury is one of the most common side effects of radiotherapy. However, there is no ideal therapy method except for symptomatic treatment in the clinic. Xuebijing (XBJ) is a traditional Chinese medicine, used to treat sepsis by injection. In this study, the protective effects of XBJ on radiation-induced intestinal injury (RIII) and its mechanism were explored. Methods:The effect of XBJ on survival of irradiated C57BL/6 mice was monitored.Histological changes including the number of crypts and the length of villi were evaluated by H&E. The expression of Lgr5 + intestinal stem cells (ISCs), Ki67 + cells, villin and lysozymes were examined by immunohistochemistry. The expression of cytokines in the intestinal crypt was detected by RT-PCR. DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence. Results:In the present study, XBJ improved the survival rate of the mice after 8.0 and 9.0 Gy total body irradiation (TBI). XBJ attenuated structural damage of the small intestine, maintained regenerative ability and promoted proliferation and differentiation of crypt cells, decreased apoptosis rate and reduced DNA damage in the intestine. Elevation of IL-6 and TNFα was limited, but IL-1, TNF-𝛽 and IL-10 levels were increased in XBJ-treated group after irradiation. The expression of Bax and p53 were decreased after XBJ treatment. Conclusions:Taken together, XBJ provides a protective effect on RIII by inhibiting inflammation and blocking p53-related apoptosis pathway.

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β-Naphthoflavone Activation of the Ah Receptor Alleviates Irradiation-Induced Intestinal Injury in Mice

Cited by 9 publications

References 41 publications

Potential Dietary and Therapeutic Strategies Involving Indole-3-Carbinole in Preclinical Models of Intestinal Inflammation

Potential Dietary and Therapeutic Strategies Involving Indole-3-Carbinole in Preclinical Models of Intestinal Inflammation

The Protective Effects of Sour Orange (Citrus aurantium L.) Polymethoxyflavones on Mice Irradiation-Induced Intestinal Injury

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

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