1. Chitosan and chitosan/PEG nanoparticles loaded with indole-3-carbinol: Characterization, computational study and potential effect on human bladder cancer cells.
期刊:Materials science & engineering. C, Materials for biological applications
日期:2021-03-31
DOI :10.1016/j.msec.2021.112089
Indole-3-carbinol (I3C) is a plant molecule known to be active against several types of cancer, but some chemical characteristics limit its clinical applications. In order to overcome these limitations, polymeric nanoparticles can be used as carrier systems for targeted delivery of I3C. In this study, chitosan and chitosan/polyethylene glycol nanoparticles (CS NP and CS/PEG NP, respectively) were prepared to encapsulate I3C by ionic gelation method. The polymeric nanoparticles were characterized by Dynamic Scattering Light (DLS), Zeta Potential (ZP), Fourier Transform Infrared (FTIR) spetroscopy, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Field Emission Gun Scanning Electron Microscopy (FEG-SEM). I3C release testing was performed at an acidic media and the interactions between I3C and chitosan or PEG were evaluated by Density Functional Theory (DFT). Cytotoxicity of nanoparticles in bladder cancer T24 cell line was evaluated by the Methyl-thiazolyl-tetrazolium (MTT) colorimetric assay. The average size of the nanoparticles was observed to be in the range from 133.3 ± 3.7 nm to 180.4 ± 2.7 nm with a relatively homogeneous distribution. Samples had relatively high positive zeta potential values (between +20.3 ± 0.5 mV and + 24.3 ± 0.5 mV). Similar encapsulation efficiencies (about 80%) for both nanoparticles were obtained. Physicochemical and thermal characterizations pointed to the encapsulation of I3c. electron microscopy showed spherical particles with smooth or ragged surface characteristics, depending on the presence of PEG. The mathematical fitting of the release profile demonstrated that I3C-CS NP followed the Higuchi model whereas I3C-CS/PEG NP the Korsmeyer-Peppas model. Chemical differences between the nanoparticles as based on the I3C/CS or I3C/PEG interactions were demonstrate by computational characterization. The assessment of cell viability by the MTT test showed that the presence of both free I3C and I3C-loaded nanoparticles lead to statistically significant reduction in T24 cells viability in the concentrations from 500 to 2000 μM, when comparison to the control group after 24 h of exposure. Thus, CS and CS/PEG nanoparticles present as feasible I3C carrier systems for cancer therapy.
添加收藏
创建看单
引用
2区Q1影响因子: 5
跳转PDF
登录
英汉
2. Indole-3-Carbinol Inhibits Infection through Multiple Pathways Including Reduction of Bacterial Adhesion and Enhancement of Cytotoxic T Cell Activity.
2. 吲哚-3-甲醇可通过多种途径抑制感染,包括减少细菌粘附和增强细胞毒性T细胞活性。
期刊:Nutrients
日期:2020-03-27
DOI :10.3390/nu12040917
Intestinal inflammation is associated with an increased risk of developing colorectal cancer and may result from dysregulated responses to commensal bacteria or exposure to bacterial pathogens. Dietary modulation of intestinal inflammation may protect against development of colon cancer. However, the precise diet-derived components and underlying mechanisms remain elusive. () induces acute intestinal inflammation and has been used to study the role of inflammation in the susceptibility to colon cancer. Here we examine the effects of indole-3-carbinol (I3C), a dietary compound with anticarcinogenic properties, on intestinal immune and inflammatory responses to infection and adhesion to colonic cells in vitro. C57BL/6J mice were fed a diet with/without 1 μmol/g I3C and infected with . Compared to infected mice fed with a control diet, consumption of a 1 μmol I3C/g diet significantly reduced fecal excretion of , colonization of the colon, and reduced colon crypt hyperplasia. Furthermore, expression of -induced inflammatory markers such as IL-17A, IL-6, and IL1β were attenuated in infected mice fed with the I3C diet, compared to mice fed a control diet. The expression of cytotoxic T cell markers CD8 and FasL mRNA were increased in I3C-fed infected mice. In-vitro, I3C inhibited growth and adhesion to Caco-2 cells. I3C alleviates -induced murine colitis through multiple mechanisms including inhibition of growth and adhesion to colonic cells in vitro and enhancement of cytotoxic T cell activity.
添加收藏
创建看单
引用
1区Q1影响因子: 8.2
跳转PDF
登录
英汉
3. Heating conversion of indole-3-carbinol into -substituted oligomers with anti-melanoma effect.
3. 吲哚 - 3 - 甲醇加热转化为具有抗黑素瘤作用的取代低聚物。
期刊:Food chemistry: X
日期:2024-04-24
DOI :10.1016/j.fochx.2024.101410
Cruciferous vegetables (CVs) are globally consumed with some health benefits believed to arise from indole-3-carbinol (I3C), a labile phytochemical liberated from indole glucosinolates, but few reports describe the effect of cooking on I3C reactions. Here, we present heat-promoted direct conversions of I3C in broccoli florets into indole derivatives, which are unique in the -indolylmethylation and -hydroxymethylation of indole nuclei by 3-methyleneindole and formaldehyde formed in situ from the I3C dehydration and the dimerization of I3C to 3,3'-diindolylmethane (DIM), respectively. Such -substituted indoles were found in a range of 0.4-4.6 μg per gram of steamed broccoli florets, with a novel compound -(indol-3-ylmethyl)-3,3'-diindolylmethane (DIM-1) bio-evaluated to inhibit A375 cells with an IC value of 1.87 μM. In aggregation, the investigation discloses the promoting effect of heating on the I3C transformation in CVs and identifies DIM-1 as an anti-cancer drug candidate, and thus updates the knowledge of I3C and bioactive derivatives thereof.
添加收藏
创建看单
引用
2区Q1影响因子: 5.9
打开PDF
登录
英汉
4. Dietary Indole-3-Carbinol Activates AhR in the Gut, Alters Th17-Microbe Interactions, and Exacerbates Insulitis in NOD Mice.
4. 膳食吲哚-3-甲醇激活肠道AhR,改变Th17微生物相互作用,加重NOD小鼠胰岛炎。
期刊:Frontiers in immunology
日期:2021-01-21
DOI :10.3389/fimmu.2020.606441
The diet represents one environmental risk factor controlling the progression of type 1 diabetes (T1D) in genetically susceptible individuals. Consequently, understanding which specific nutritional components promote or prevent the development of disease could be used to make dietary recommendations in prediabetic individuals. In the current study, we hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will regulate the progression of T1D in nonobese diabetic (NOD) mice. During digestion, I3C is metabolized into ligands for the aryl hydrocarbon receptor (AhR), a transcription factor that when systemically activated prevents T1D. In NOD mice, an I3C-supplemented diet led to strong AhR activation in the small intestine but minimal systemic AhR activity. In the absence of this systemic response, the dietary intervention led to exacerbated insulitis. Consistent with the compartmentalization of AhR activation, dietary I3C did not alter T helper cell differentiation in the spleen or pancreatic draining lymph nodes. Instead, dietary I3C increased the percentage of CD4RORγtFoxp3 (Th17 cells) in the lamina propria, intraepithelial layer, and Peyer's patches of the small intestine. The immune modulation in the gut was accompanied by alterations to the intestinal microbiome, with changes in bacterial communities observed within one week of I3C supplementation. A transkingdom network was generated to predict host-microbe interactions that were influenced by dietary I3C. Within the phylum Firmicutes, several genera (, 9, and unclassified Lachnospiraceae) were negatively regulated by I3C. Using AhR knockout mice, we validated that is negatively regulated by AhR. I3C-mediated microbial dysbiosis was linked to increases in CD25 Th17 cells. Collectively, these data demonstrate that site of AhR activation and subsequent interactions with the host microbiome are important considerations in developing AhR-targeted interventions for T1D.
添加收藏
创建看单
引用
3区Q1影响因子: 5.4
跳转PDF
登录
英汉
5. Immune and microRNA responses to infection and indole-3-carbinol during colitis.
5. 在结肠炎期间免疫和microRNA对感染和吲哚-3-甲醇的反应。
作者:Alkarkoushi Rasha Raheem , Hui Yvonne , Tavakoli Abbas S , Singh Udai , Nagarkatti Prakash , Nagarkatti Mitzi , Chatzistamou Ioulia , Bam Marpe , Testerman Traci L
期刊:World journal of gastroenterology
日期:2020-08-28
DOI :10.3748/wjg.v26.i32.4763
BACKGROUND:Indole-3-carbinol (I3C) and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models, including colitis induced by dextran sulfate sodium (DSS). MicroRNAs (miRNAs) are also gaining traction as potential therapeutic agents or diagnostic elements. Enterohepatic (EHH) species are associated with an increased risk of inflammatory bowel disease, but little is known about how these species affect the immune system or response to treatment. AIM:To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH species compare with responses to DSS and inflammatory bowel disease. METHODS:We infected C57BL/6 mice with (), with and without DSS and I3C treatment. Pathological responses were evaluated by histological examination, symptom scores, and cytokine responses. MiRNAs analysis was performed on mesenteric lymph nodes to further evaluate the regional immune response. RESULTS: infection alone caused colonic inflammation and upregulated proinflammatory, macrophage-associated cytokines in the colon similar to changes seen in DSS-treated mice. Further upregulation occurred upon treatment with DSS. infection caused broad changes in mesenteric lymph node miRNA expression, but colitis-associated miRNAs were regulated similarly in infected and uninfected, DSS-treated mice. In spite of causing colitis exacerbation, infection did not prevent disease amelioration by I3C. I3C normalized both macrophage- and T cell-associated cytokines. CONCLUSION:Thus, I3C may be useful for inflammatory bowel disease patients regardless of EHH infection. The miRNA changes associated with I3C treatment are likely the result of, rather than the cause of immune response changes.
添加收藏
创建看单
引用
打开PDF
登录
英汉
6. Indole-3-Carbinol-Dependent Aryl Hydrocarbon Receptor Signaling Attenuates the Inflammatory Response in Experimental Necrotizing Enterocolitis.
6. 吲哚-3-甲醇依赖的芳香烃受体信号传导减弱实验性坏死性小肠结肠炎的炎症反应。
作者:Nolan Lila S , Mihi Belgacem , Agrawal Pranjal , Gong Qingqing , Rimer Jamie M , Bidani Shay S , Gale Sarah E , Goree Martin , Hu Elise , Lanik Wyatt E , Huang Elizabeth , Bando Jennifer K , Liu Victoria , Lewis Angela N , Bustos Aiza , Hodzic Zerina , Laury Marie L , Good Misty
期刊:ImmunoHorizons
日期:2021-04-27
DOI :10.4049/immunohorizons.2100018
Necrotizing enterocolitis (NEC) causes significant morbidity and mortality in premature infants; therefore, the identification of therapeutic and preventative strategies against NEC remains a high priority. The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) is well known to contribute to the regulation of intestinal microbial communities and amelioration of intestinal inflammation. However, the role of AhR signaling in NEC is unclear. Experimental NEC was induced in 4-d-old wild-type mice or mice lacking AhR expression in the intestinal epithelial cells or AhR expression in CD11c cells (AhR) by subjecting animals to twice daily hypoxic stress and gavage feeding with formula supplemented with LPS and enteric bacteria. During NEC, compared with wild-type mice treated with vehicle, littermates treated with an AhR proligand, indole-3-carbinol, had reduced expression of and a scavenger receptor that mediates dendritic cell activation and the recognition and clearance of bacterial pathogens by macrophages. Furthermore, indole-3-carbinol treatment led to the downregulation of genes involved in cytokine and chemokine, as revealed by pathway enrichment analysis. AhR expression in the intestinal epithelial cells and their cre-negative mouse littermates were similarly susceptible to experimental NEC, whereas AhR mice with NEC exhibited heightened inflammatory responses compared with their cre-negative mouse littermates. In seeking to determine the mechanisms involved in this increased inflammatory response, we identified the Tim-4 monocyte-dependent subset of macrophages as increased in AhR mice compared with their cre-negative littermates. Taken together, these findings demonstrate the potential for AhR ligands as a novel immunotherapeutic approach to the management of this devastating disease.
添加收藏
创建看单
引用
1区Q1影响因子: 6.1
跳转PDF
登录
英汉
7. Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22-dependent manner.
7. 吲哚-3-咔啉可防止结肠炎和相关的微生物消带菌,以IL-22依赖性方式。
期刊:JCI insight
日期:2020-01-16
DOI :10.1172/jci.insight.127551
Colitis, an inflammatory bowel disease, is caused by a variety of factors, but luminal microbiota are thought to play crucial roles in disease development and progression. Indole is produced by gut microbiota and is believed to protect the colon from inflammatory damage. In the current study, we investigated whether indole-3-carbinol (I3C), a naturally occurring plant product found in numerous cruciferous vegetables, can prevent colitis-associated microbial dysbiosis and attempted to identify the mechanisms. Treatment with I3C led to repressed colonic inflammation and prevention of microbial dysbiosis caused by colitis, increasing a subset of gram-positive bacteria known to produce butyrate. I3C was shown to increase production of butyrate, and when mice with colitis were treated with butyrate, there was reduced colonic inflammation accompanied by suppression of Th17 and induction of Tregs, protection of the mucus layer, and upregulation in Pparg expression. Additionally, IL-22 was increased only after I3C but not butyrate administration, and neutralization of IL-22 prevented the beneficial effects of I3C against colitis, as well as blocked I3C-mediated dysbiosis and butyrate induction. This study suggests that I3C attenuates colitis primarily through induction of IL-22, which leads to modulation of gut microbiota that promote antiinflammatory butyrate.
添加收藏
创建看单
引用
1区Q1影响因子: 8.3
英汉
8. Gut microbiome and metabolomic profiles reveal the antiatherosclerotic effect of indole-3-carbinol in high-choline-fed ApoE mice.
期刊:Phytomedicine : international journal of phytotherapy and phytopharmacology
日期:2024-04-10
DOI :10.1016/j.phymed.2024.155621
BACKGROUND:The metabolites produced from choline contribute to atherosclerosis (AS) pathogenesis, and the gut microbiota is redundantly essential for this process. Indole-3-carbinol (I3C), found in cruciferous vegetables such as broccoli, cabbage, cauliflower and brussels sprouts, helps prevent hyperlipidemia, maintain the gut microbiota balance, and decrease the production of trimethylamine-N-oxide (TMAO) from choline in the diet. PURPOSE:The objective of this research was to investigate the impact of I3C on choline-induced AS and to further elucidate the underlying mechanism involved. METHODS:AS models of high-choline-induced ApoE mice and TMAO-promoted foamy macrophages were established to observe the effect of I3C on the formation of atherosclerotic plaques and foam cells and changes in AS-related indicators (including blood biochemical indicators, TMA, TMAO, SRA, and SRB1), and integrated analyses of the microbiome and metabolome were used to reveal the mechanism of action of I3C. RESULTS:We found that I3C inhibited high-choline-induced atheroma formation (50-100 mg/kg/d, in vivo) and slightly improved the lipid profile (15 mg/kg/d, in vivo). Moreover, I3C suppressed lipid influx at a concentration of 40 µmol/L in vitro, enhanced the diversity of the gut microbiota and the abundance of the phylum Verrucomicrobia, and consequently modified the gut microbial metabolites at a dosage of 50 mg/kg/d in the mice. Associative analyses based on microbiome and metabolomics revealed that 1-methyladenosine was a key modulator of the protective effect of I3C against AS in high-choline-induced ApoE mice. CONCLUSION:These findings demonstrate for the first time that I3C ameliorates AS progression through remodeling of the gut microbiome and metabolomics, which paves the way for the possible therapeutic use of this vegetable-derived natural compound and may reduce the clinical severity of AS-related cardiovascular diseases.
添加收藏
创建看单
引用
2区Q1影响因子: 7.5
英汉
9. Indole-3-carbinol and its main derivative 3,3'-diindolylmethane: Regulatory roles and therapeutic potential in liver diseases.
Indole-3-carbinol (I3C), a compound found in cruciferous vegetables, has shown significant efficacy in treating both cancerous and non-cancerous diseases. Its primary derivative, 3,3'-diindolylmethane (DIM), formed during digestion, also exhibits similar therapeutic benefits. In liver disorders, I3C and DIM exhibit dual roles by inhibiting and promoting hepatocellular carcinoma (HCC) and providing relief for nonmalignant liver diseases, such as acute liver injury (ALI), hepatic fibrosis, nonalcoholic fatty liver disease (NAFLD), and alcohol-related liver disease (ALD). Mechanistically, I3C and DIM modulate various pathophysiological processes, including cell proliferation, apoptosis, oxidative stress, and lipogenesis. This review aims to enhance researchers' understanding of the regulatory roles of I3C and DIM in these liver diseases and explore the potential of plant-derived substances in liver disease treatment.
添加收藏
创建看单
引用
2区Q1影响因子: 5.1
跳转PDF
登录
英汉
10. Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.
Hydrolysis of glucobrassicin by plant or bacterial myrosinase produces multiple indoles predominantly indole-3-carbinol (I3C). I3C and its major product, 3,3'-diindolylmethane (DIM), are effective cancer chemopreventive agents in pre-clinical models and show promise in clinical trials. The pharmacokinetics/pharmacodynamics of DIM have been studied in both rodents and humans and urinary DIM is a proposed biomarker of dietary intake of cruciferous vegetables. Recent clinical studies at Oregon State University show surprisingly robust metabolism of DIM with mono- and di-hydroxylation followed by conjugation with sulfate or glucuronic acid. DIM has multiple mechanisms of action, the most well-characterized is modulation of aryl hydrocarbon receptor (AHR) signaling. In rainbow trout dose-dependent cancer chemoprevention by dietary I3C is achieved when given prior to or concurrent with aflatoxin B, polycyclic aromatic hydrocarbons, nitrosamines or direct acting carcinogens such as N-methyl-N'-nitro-nitrosoguanidine. Feeding pregnant mice I3C inhibits transplacental carcinogenesis. In humans much of the focus has been on chemoprevention of breast and prostate cancer. Alteration of cytochrome P450-dependent estrogen metabolism is hypothesized to be an important driver of DIM-dependent breast cancer prevention. The few studies done to date comparing glucobrassicin-rich crucifers such as Brussels sprouts with I3C/DIM supplements have shown the greater impact of the latter is due to dose. Daily ingestion of kg quantities of Brussels sprouts is required to produce levels of DIM achievable by supplementation. In clinical trials these supplement doses have elicited few if any adverse effects. Sulforaphane from glucoraphanin can act synergistically with glucobrassicin-derived DIM and this may lead to opportunities for combinatorial approaches (supplement and food-based) in the clinic.
添加收藏
创建看单
引用
2区Q1影响因子: 5.6
英汉
11. Indole-3-carbinol ameliorates ovarian damage in female old mice through Nrf2/HO-1 pathway activation.
11. 吲哚 - 3 - 甲醇通过激活 Nrf2 / HO - 1 通路改善雌性老年小鼠卵巢损伤。
期刊:Biochemical pharmacology
日期:2024-04-04
DOI :10.1016/j.bcp.2024.116193
Ovarian aging leads to infertility and birth defects. We aimed to clarify the role of Indole-3-carbinol (I3C) in resistance to oxidative stress, apoptosis, and fibrosis in ovarian aging. I3C was administered via intraperitoneal injection for 3 weeks in young or old mice. Immunohistochemistry; Masson, Sirius red, and TUNEL staining; follicle counting; estrous cycle analysis; and Western blotting were used for validating the protective effect of I3C against ovarian senescence. Human granulosa-like tumor cell line and primary granulosa cells were used for in vitro assay. The results indicated that I3C inhibited ovarian fibrosis and apoptosis while increasing the number of primordial follicles. Mechanistic studies have shown that I3C promoted the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2) and upregulated the expression of heme oxygenase 1 (HO-1). Additionally, I3C increased cell viability and decreased lactate dehydrogenase, malondialdehyde, reactive oxygen species and JC-1 levels. Furthermore, the antioxidant effect of I3C was found to be dependent on the activation of Nrf2 and HO-1, as demonstrated by the disappearance of the effect upon inhibition of Nrf2 expression. In conclusion, I3C can alleviate the ovarian damage caused by aging and may be a protective agent to delay ovarian aging.
添加收藏
创建看单
引用
2区Q1影响因子: 4.1
跳转PDF
登录
英汉
12. Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review.
12. 揭示吲哚 - 3 - 甲醇和二吲哚甲烷的多方面药理作用:综合综述。
期刊:Plants (Basel, Switzerland)
日期:2025-03-06
DOI :10.3390/plants14050827
Cruciferae family vegetables are remarkably high in phytochemicals such as Indole-3-carbinol (I3C) and Diindolylmethane (DIM), which are widely known as nutritional supplements. I3C and DIM have been studied extensively in different types of cancers like breast, prostate, endometrial, colorectal, gallbladder, hepatic, and cervical, as well as cancers in other tissues. In this review, we summarized the protective effects of I3C and DIM against cardiovascular, neurological, reproductive, metabolic, bone, respiratory, liver, and immune diseases, infections, and drug- and radiation-induced toxicities. Experimental evidence suggests that I3C and DIM offer protection due to their antioxidant, anti-inflammatory, antiapoptotic, immunomodulatory, and xenobiotic properties. Apart from the beneficial effects, the present review also discusses the possible toxicities of I3C and DIM that are reported in various preclinical investigations. So far, most of the reports about I3C and DIM protective effects against various diseases are only from preclinical studies; this emphasizes the dire need for large-scale clinical trials on these phytochemicals against human diseases. Further, in-depth research is required to improve the bioavailability of these two phytochemicals to achieve the desirable protective effects. Overall, our review emphasizes that I3C and DIM may become potential drug candidates for combating dreadful human diseases.
添加收藏
创建看单
引用
1区Q1影响因子: 8
英汉
13. Indole-3-carbinol and chlorogenic acid combination modulates gut microbiome and attenuates nonalcoholic steatohepatitis in a murine model.
13. 吲哚 - 3 - 甲醇和绿原酸的组合在鼠模型中调节肠道微生物组并减弱非酒精性脂肪性肝炎。
期刊:Food research international (Ottawa, Ont.)
日期:2023-09-28
DOI :10.1016/j.foodres.2023.113513
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, affecting almost 32% of the population and ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Recent findings indicate that the fast-growing prevalence of NAFLD might be linked to adherence to a Westernized diet (WD), mostly composed of fat/sugar-enriched foods. The WD has been reportedly targeted as a potential driver of gut-liver axis unbalance, suggesting a major role in NASH. On the other hand, bioactive food compounds feature as a potential chemopreventive strategy against NASH, due to their beneficial effects (i.e, anti-inflammatory/oxidant activity and modulation of gut microbiome). Brassicaceae vegetables are known for their high amount of isothiocyanates and polyphenols, as indole-3-carbinol (I3C) and chlorogenic acid (CGA). Thus, we sought to assess the effects of human relevant doses of I3C and CGA isolated or in combination (5/125 mg/Kg of body weight, respectively) on a diet/chemical-induced murine model of NASH. I3C + CGA oral treatment diminished NAFLD activity score (NAS) (p < 0.0001), as well as alleviated the hepatic lipid (p = 0.0011) accumulation, prevented hepatic stellate cell (HSC) activation (p < 0.0001), and subsequent fibrosis (p < 0.0001). The combination also reduced the number of both hepatic CD68-positive macrophages (p < 0.0001) and cleaved caspase-3 hepatocytes (p < 0.0001) and diminished the malondialdehyde levels (p = 0.0155). Additionally, the combination of I3C + CGA restored the relative abundance of Alistipes (p = 0.0299), Allobaculum (p = 0.0014), Bacteroides (p = 0.0046), and Odoribacter (p = 0.0030) bacteria genera on the gut microbiome. Taken together, these findings show that the combination of I3C + CGA at populational-relevant ingestion, rather than the I3C or CGA alone, was able to modulate gut microbiome and attenuate NASH in this hybrid model mouse.
添加收藏
创建看单
引用
3区Q1影响因子: 3.9
打开PDF
登录
英汉
14. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles.
14. 人类芳香烃受体到感微生物群衍生的吲哚的适应。
作者:Hubbard Troy D , Murray Iain A , Bisson William H , Lahoti Tejas S , Gowda Krishne , Amin Shantu G , Patterson Andrew D , Perdew Gary H
期刊:Scientific reports
日期:2015-08-03
DOI :10.1038/srep12689
Ligand activation of the aryl hydrocarbon (AHR) has profound effects upon the immunological status of the gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at the mucosal interface. However, the identity of the ligand(s) responsible for such AHR-mediated activation within the gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction and ligand structure activity analyses together with in silico modeling of the AHR ligand binding domain to identify indole, a microbial tryptophan metabolite, as a human-AHR selective agonist. Human AHR, acting as a host indole receptor may exhibit a unique bimolecular (2:1) binding stoichiometry not observed with typical AHR ligands. Such bimolecular indole-mediated activation of the human AHR within the gastrointestinal tract may provide a foundation for inter-kingdom signaling between the enteric microflora and the immune system to promote commensalism within the gut.
添加收藏
创建看单
引用
3区Q1影响因子: 3.4
跳转PDF
登录
英汉
15. Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension.
The aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, inappropriate RAS activation could impair cardiac tolerance to I/R injury. Experiments were performed in male transgenic rats with inducible hypertension. The early phase of ANG II-dependent hypertension was induced by 5 days and the late phase by the 13 days dietary indole-3-carbinol (I3C) administration. Noninduced rats served as controls. Echocardiography and pressure-volume analysis were performed, angiotensins' levels were measured and cardiac tolerance to ischemia/reperfusion injury was studied. The infarct size was significantly reduced (by 50%) in 13 days I3C-induced hypertensive rats with marked cardiac hypertrophy, this reduction was abolished by losartan treatment. In the late phase of hypertension there are indications of a failing heart, mainly in reduced preload recruitable stroke work (PRSW), but only nonsignificant trends in worsening of some other parameters, showing that the myocardium is in a compensated phase. The influence of the RAS depends on the balance between the vasoconstrictive and the opposed vasodilatory axis. In the initial stage of hypertension, the vasodilatory axis of the RAS prevails, and with the development of hypertension the vasoconstrictive axis of the RAS becomes stronger. We observed a clear effect of AT1 receptor blockade on maximum pressure in left ventricle, cardiac hypertrophy and ANG II levels. In conclusion, we confirmed improved cardiac tolerance to I/R injury in hypertensive hypertrophied rats and showed that, in the late phase of hypertension, the myocardium is in a compensated phase.
添加收藏
创建看单
引用
4区Q2影响因子: 3.1
英汉
16. Indole-3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model.
16. 吲哚-3-甲醇改善脑缺血中风模型神经行为症状。
作者:Paliwal Pankaj , Chauhan Gaurav , Gautam Deepa , Dash Debabrata , Patne Shashikant C U , Krishnamurthy Sairam
期刊:Naunyn-Schmiedeberg's archives of pharmacology
日期:2018-03-30
DOI :10.1007/s00210-018-1488-2
Stroke is one of the most common causes of death worldwide and also responsible for permanent disability. Ischemic stroke has been found to affect 80% of stroke patients. Recombinant tissue plasminogen activator (rtPA) is the widely used drug for the ischemic stroke with narrow therapeutic window. Indole-3-carbinol (I3C) is a natural compound obtained from brassica species having antithrombotic activity. Middle cerebral artery occlusion (MCAO) model was used followed by reperfusion after 2 h of ischemia for the evaluation of the I3C against ischemic stroke. After reperfusion, I3C (12.5, 25, and 50 mg/kg) was given by oral route once daily and continued up to the 14th day. Behavioral studies including postural reflex, forelimb placing, and cylinder tests showed I3C attenuated the MCAO-induced increase in average score and asymmetry score efficiently. Mean cerebral blood flow (CBF) was improved by treatment with I3C (12.5 mg/kg) by 60% of baseline at 6 h. I3C inhibited ADP-induced platelet aggregation and reduced ischemic volume significantly. It also inhibited in vitro the ADP-induced platelet aggregation in healthy human volunteers. I3C improves behavioral scores and mean CBF after focal cerebral ischemia in rats. Furthermore, I3C showed prophylactic anti-thrombotic activity against carrageenan induced tail thrombosis. Therefore, preclinical evidence points to I3C as a potential candidate for use in cerebral ischemic stroke.
添加收藏
创建看单
引用
3区Q3影响因子: 3
英汉
17. Indole-3-carbinol mitigates oxidative stress and inhibits inflammation in rat cerebral ischemia/reperfusion model.
17. 减轻氧化应激,抑制炎症吲哚- 3 -甲醇在老鼠脑缺血/再灌注模型。
期刊:Biochimie
日期:2023-04-27
DOI :10.1016/j.biochi.2023.04.018
Ischemia is a significant pathogenetic factor of stroke with very limited treatment options. The objective of our research was to evaluate the protective properties of indole-3-carbinol (I3C) and its effect on redox status parameters, inflammation, and apoptosis intensity in cerebral ischemia/reperfusion injury (CIRI) in rats. I3C administration to CIRI rats decreased levels of oxidative stress markers and improved aerobic metabolism compared to the animals with CIRI. A decrease in myeloperoxidase activity, proinflammatory cytokines mRNA levels, and expression of redox-sensitive factor Nuclear Factor-κB was observed in rats with CIRI that received I3C. I3C-treated rats with pathology showed decreased caspase activity and apoptosis-inducing factor expression, compared to the animals in the CIRI group. Obtained data indicate that I3C has a neuroprotective and anti-ischemic effect in CIRI that may be related to its antioxidant properties and ability to reduce the inflammatory response and apoptosis.
期刊:Cellular and molecular gastroenterology and hepatology
日期:2021-08-25
DOI :10.1016/j.jcmgh.2021.08.014
BACKGROUND & AIMS:The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR) can sense xenobiotics, dietary, microbial, and metabolic cues. Roles of Ahr in intestinal epithelial cells (IECs) have been much less elucidated compared with those in intestinal innate immune cells. Here, we explored whether the IEC intrinsic Ahr could modulate the development of alcohol-related liver disease (ALD) via the gut-liver axis. METHODS:Mice with IEC specific Ahr deficiency (Ahr) were generated and fed with a control or ethanol diet. Alterations of intestinal microbiota and metabolites were investigated by 16S ribosomal RNA sequencing, metagenomics, and untargeted metabolomics. AHR agonists were used to evaluate the therapeutic potentials of intestinal Ahr activation for ALD treatment. RESULTS:Ahr mice showed more severe liver injury after ethanol feeding than control mice. Ahr deficiency in IECs altered the intestinal metabolite composition, creating an environment that promoted the overgrowth of Helicobacter hepaticus and Helicobacter ganmani in the gut, enhancing their translocation to mesenteric lymph nodes and liver. Among the altered metabolites, isobutyric acid was increased in the cecum of ethanol-fed Ahr mice relative to control mice. Furthermore, both H.hepaticus and isobutyric acid administration aggravated ethanol-induced liver injury in vivo and in vitro. Supplementation with AHR agonists, 6-formylindolo[3,2-b]carbazole and indole-3-carbinol, protected mice from ALD development by specifically activating intestinal Ahr without affecting liver Ahr function. Alcoholic patients showed lower intestinal AHR expression and higher H.hepaticus levels compared with healthy individuals. CONCLUSIONS:Our results indicate that targeted restoration of IEC intrinsic Ahr function may present as a novel approach for ALD treatment.
添加收藏
创建看单
引用
3区Q1影响因子: 4.9
跳转PDF
登录
英汉
19. Aryl Hydrocarbon Receptor Regulates Muc2 Production Independently of IL-22 during Colitis.
19. 芳基烃受体在结肠炎期间独立于 IL - 22 调节 Muc2 产生。
期刊:International journal of molecular sciences
日期:2024-02-18
DOI :10.3390/ijms25042404
We previously reported that an aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective at reducing colitis severity through immune cell-mediated interleukin-22 (IL-22) production. Intestinal epithelial cells (IECs) are also involved in regulating colitis, so we investigated their AhR-mediated mechanisms in the current report. A transcriptome analysis of IECs in wildtype (WT) mice revealed that during colitis, I3C regulated select mucin proteins, which could be attributed to goblet cell development. To address this, experiments under in vivo colitis (mice) or in vitro colon organoid conditions were undertaken to determine how select mucin proteins were altered in the absence or presence of AhR in IECs during I3C treatment. Comparing WT to IEC-specific AhR knockout mice (AhR), the results showed that AhR expression was essential in IECs for I3C-mediated protection during colitis. AhR-deficiency also impaired mucin protein expression, particularly mucin 2 (Muc2), independently of IL-22. Collectively, this report highlights the important role of AhR in direct regulation of Muc2. These results provide justification for future studies aimed at determining how AhR might regulate select mucins through mechanisms such as direct transcription binding to enhance production.
添加收藏
创建看单
引用
3区Q1影响因子: 4.8
跳转PDF
登录
英汉
20. Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice.
Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.
Previous studies have suggested that myocardial inflammation plays a critical role after ischemic myocardial infarction (MI); however, the underlying mechanisms still need to be fully elucidated. WW domain-containing ubiquitin E3 ligase 1 (WWP1) is considered as an important therapeutic target for cardiovascular diseases due to its crucial function in non-ischemic cardiomyopathy, though it remains unknown whether targeting WWP1 can alleviate myocardial inflammation and ischemic injury post-MI. Recombinant adeno-associated virus 9 (rAAV9)-cTnT-mediated WWP1 or Kruppel-like factor 15 (KLF15) gene transfer and a natural WWP1 inhibitor Indole-3-carbinol (I3C) were used to determine the WWP1 function in cardiomyocytes. Cardiac function, tissue injury, myocardial inflammation, and signaling changes in the left ventricular tissues were analyzed after MI. The mechanisms underlying WWP1 regulation of cardiomyocyte phenotypes were determined using the adenovirus system. We found that WWP1 expression was up-regulated in cardiomyocytes located in the infarct border at the early phase of MI and in hypoxia-treated neonatal rat cardiac myocytes (NRCMs). Cardiomyocyte-specific WWP1 overexpression augmented cardiomyocyte apoptosis, increased infarct size and deteriorated cardiac function. In contrast, inhibition of WWP1 in cardiomyocytes mitigated MI-induced cardiac ischemic injury. Mechanistically, WWP1 triggered excessive cardiomyocyte inflammation after MI by targeting KLF15 to catalyze K48-linked polyubiquitination and degradation. Ultimately, WWP1-mediated degradation of KLF15 contributed to the up-regulation of p65 acetylation, and activated the inflammatory signaling of MAPK in ischemic myocardium and hypoxia-treated cardiomyocytes. Thus, targeting of WWP1 by I3C protected against cardiac dysfunction and remodeling after MI. Our study provides new insights into the previously unrecognized role of WWP1 in cardiomyocyte inflammation and progression of ischemic injury induced by MI. Our findings afford new therapeutic options for patients with ischemic cardiomyopathy.
添加收藏
创建看单
引用
3区Q1影响因子: 3.9
跳转PDF
登录
英汉
22. Indole-3-carbinol (I3C) reduces apoptosis and improves neurological function after cerebral ischemia-reperfusion injury by modulating microglia inflammation.
Indole-3-carbinol(I3C) is a tumor chemopreventive substance that can be extracted from cruciferous vegetables. Indole-3-carbinol (I3C) has been shown to have antioxidant and anti-inflammatory effects. In this study, we investigated the cerebral protective effects of I3C in an in vivo rats model of middle cerebral artery occlusion (MCAO). 8-10 Week-Old male SD rat received I3C (150 mg/kg, once daily) for 3 days and underwent 3 h of middle cerebral artery occlusion (MCAO) followed by reperfusion. The results showed that I3C pretreatment (150 mg/kg, once daily) prevented CIRI-induced cerebral infarction in rats. I3C pretreatment also decreased the mRNA expression levels of several apoptotic proteins, including Bax, caspase-3 and caspase-9, by increasing the mRNA expression levels of the anti-apoptotic protein Bcl-2. Inhibited apoptosis in the brain cells of MCAO rats. In addition, we found that I3C pretreatment reduced neuronal loss, promoted neurological recovery after ischemia-reperfusion injury and increased seven-day survival in MCAO rats. I3C pretreatment also significantly reduced the expression of inducible nitric oxide synthase (INOS), interleukin-1β (IL-1β) and interleukin-6 (IL-6) mRNA in ischemic brain tissue; Increased expression of interleukin-4 (IL-4) and interleukin-10 (IL-10) mRNA. At the same time, I3C pretreatment significantly decreased the expression of the M1 microglial marker IBA1 after cerebral ischemia-reperfusion injury and increased the expression of these results in the M2 microglial marker CD206. I3C pretreatment also significantly decreased apoptosis and death of HAPI microglial cells after hypoxia induction, decreased interleukin-1β (IL-1β) and interleukin-6 (IL-6) mRNA The expression of interleukin-4 (IL-4) and interleukin-10 (IL-10) mRNAs was increased. These results suggest that I3C protects the brain from CIRI by regulating the anti-inflammatory and anti-apoptotic effects of microglia.