1.Effect of Qingchang Suppository on intestinal permeability in rats with ulcerative colitis.
Chinese Journal of Integrated Traditional and Western Medicine 2010;30(10):1087-1090
OBJECTIVETo observe the effect of Qingchang Suppository (QCS, a Chinese herbal preparation) on intestinal permeability in rat ulcerative colitis (UC) model induced by trinitrobenzene sulforic acid, and to explore the mechanism of QCS for healing the ulceration.
METHODSLabelled by FITC-dextran 4 000 (FD-4), the permeability of colonic membrane in UC rat and effect of QCS on it were observed in vitro and in vivo.
RESULTSIn vivo study showed that the colonic FD-4 permeability of UC rat was increased significantly, being 6-fold of normal in 30 min. After treated with QCS of high/moderate dosage, it significantly attenuated to different degrees (P < 0.05). FD-4 permeability coefficient (Papp) determination in vitro showed that Papp in model rats increased to (5.001 +/- 1.316) x10(-8) cm/s in 120 min, being 2.5-fold of control; and which could be decreased by high/moderate dose QCS effectively (P < 0.05).
CONCLUSIONQCS could suppress the high colonic permeability in UC model rats, improve the barrier function of intestinal membrane and promote the healing of ulceration. Qingchang Suppository; ulcerative colitis; intestinal permeability in UC model rats, improve the barrier function of intestinal membrane and promote the healing of ulceration.
Animals ; Cell Membrane Permeability ; drug effects ; Colitis, Ulcerative ; chemically induced ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Intestinal Mucosa ; physiology ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Suppositories ; Trinitrobenzenesulfonic Acid
2.Norisoboldine, a natural aryl hydrocarbon receptor agonist, alleviates TNBS-induced colitis in mice, by inhibiting the activation of NLRP3 inflammasome.
Qi LV ; Kai WANG ; Si-Miao QIAO ; Yue DAI ; Zhi-Feng WEI
Chinese Journal of Natural Medicines (English Ed.) 2018;16(3):161-174
Although the etiology of inflammatory bowel disease is still uncertain, increasing evidence indicates that the excessive activation of NLRP3 inflammasome plays a major role. Norisoboldine (NOR), an alkaloid isolated from Radix Linderae, has previously been demonstrated to inhibit inflammation and IL-1β production. The present study was to examine the effect of NOR on colitis and the underlying mechanism related to NLRP3 inflammasome activation. Our results showed that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Moreover, it significantly reduced expressions of cleaved IL-1β, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1 cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL-1β but not ASC induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, NOR could activate aryl hydrocarbon receptor (AhR) in THP-1 cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90 complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter activity and binding activity of AhR/ARNT/XRE. Both siAhR and α-naphthoflavone (α-NF) markedly diminished the inhibition of NOR on NLRP3 inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR or α-NF treatment. Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling pathway.
Alkaloids
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administration & dosage
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Animals
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Colitis
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chemically induced
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drug therapy
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genetics
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immunology
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Drugs, Chinese Herbal
;
administration & dosage
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Humans
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Inflammasomes
;
drug effects
;
immunology
;
Interleukin-1beta
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genetics
;
immunology
;
Lindera
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chemistry
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Male
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Mice
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Mice, Inbred BALB C
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NF-kappa B
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genetics
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immunology
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Receptors, Aryl Hydrocarbon
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agonists
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genetics
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metabolism
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Trinitrobenzenesulfonic Acid
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adverse effects
3.Efficacy of topical versus oral 5-aminosalicylate for treatment of 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats.
Jin LI ; Cheng CHEN ; Xiao-nian CAO ; Gui-hua WANG ; Jun-bo HU ; Jing WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(1):59-65
5-aminosalicylic acid (5-ASA) is drug of choice for the treatment of ulcerative colitis (UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC. A total of 60 rats were divided into sham operation group (receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group (a release agent of mesalazine used as positive control) and oral 5-ASA group (n=12 each). Different treatments were administered 1 day after UC induction. The normal saline (2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group (7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa (7.5 g/L, twice per day, 100 mg/kg) and 5-ASA (7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography (HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.
Administration, Oral
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Administration, Topical
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Animals
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Anti-Inflammatory Agents, Non-Steroidal
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administration & dosage
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pharmacology
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Colitis, Ulcerative
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chemically induced
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drug therapy
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Colon
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drug effects
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metabolism
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pathology
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Down-Regulation
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drug effects
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Drug Administration Schedule
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Gene Expression
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drug effects
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Immunohistochemistry
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Interleukin-1beta
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genetics
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metabolism
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Interleukin-6
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genetics
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metabolism
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Intestinal Mucosa
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drug effects
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metabolism
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pathology
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Male
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Mesalamine
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administration & dosage
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pharmacology
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Peroxidase
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metabolism
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Rats
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Rats, Wistar
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Treatment Outcome
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Trinitrobenzenesulfonic Acid
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Tumor Necrosis Factor-alpha
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genetics
;
metabolism
4.Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling.
Jong Suk LEE ; Su Young PARK ; Dinesh THAPA ; Mi Kyoung CHOI ; Ill Min CHUNG ; Young Joon PARK ; Chul Soon YONG ; Han Gon CHOI ; Jung Ae KIM
Experimental & Molecular Medicine 2010;42(2):143-154
TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 microg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
Animals
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Cell Adhesion/drug effects/immunology
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Cell Extracts/administration & dosage/*pharmacology
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Chemokine CCL2/biosynthesis/genetics
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Coculture Techniques
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Colon/drug effects/*metabolism/pathology
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Grifola
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HT29 Cells
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Humans
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Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology/physiopathology
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Interleukin-8/biosynthesis/genetics
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Intestinal Mucosa/*drug effects/metabolism/pathology
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Monocytes/*drug effects/metabolism/pathology
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NF-kappa B/genetics/metabolism
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Peroxidase/metabolism
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species/metabolism
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Stomach Ulcer
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Transcription, Genetic/drug effects
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Trinitrobenzenesulfonic Acid/administration & dosage
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Tumor Necrosis Factor-alpha/*biosynthesis/genetics
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U937 Cells
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Weight Loss