Alhagi pseudalhagi Extract Exerts Protective Effects Against Intestinal Inflammation in Ulcerative Colitis by Affecting TLR4-Dependent NF-κB Signaling Pathways

Alhagi pseudalhagi Desv. Extract (APE) is the major active fraction extracted from the aerial part of Alhagi pseudalhagi Desv. In view of its application in Uyghur medicine, it may be beneficial for the treatment of ulcerative colitis (UC). The aim of the present study was to investigate the possible beneficial effects of APE on UC mice and detect the possible mechanisms underlying these effects.Methods: An acute UC model was established in mice using dextran sulfate sodium. Sixty mice were randomly divided into six groups: normal, UC model, sulfasalazine (200 mg/kg), high-dose APE (APE-H, 2.82 g/kg), middle-dose APE (APE-M, 1.41 g/kg), and low-dose APE (APE-L, 0.70 g/kg) groups. Drugs were administered by gavage for 10 days after the induction of colitis. Serum and colon tissue samples were collected from the mice during the experiment, and survival signs, body weight changes, disease activity index (DAI), colon length, and colon wet weight in mice were determined after the treatment. UC-induced damage, including inflammation and ulceration of colon mucosa, were observed by the naked eye as well as using hematoxylin and eosin staining (H&E) and scanning electron microscopy and scored according to Wallace and Keean’s criteria. We measured the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 in the serum and colon tissues using ELISA. Additionally, the relative protein levels of toll-like receptor 4 (TLR4), nuclear factor-kappa B p65 (NF-κB p65), phosphorylated NF-κB p65 at Ser536 (p-p65 Ser536), inhibitor kappa B-kinase ß (IK-Kβ), and phosphorylated IK-Kβ (Ser176/180) (p-IK-Kβ) in colonic mucosal epithelial tissues were detected using western blotting. The main functional components of APE were analyzed and confirmed by UPLC-MS/MS.Results: APE treatment repaired the UC-induced colon mucosa injury, reduced the weight loss, attenuated DAI, colon macroscopic damage index, and histological inflammation, and significantly downregulated the levels of inflammatory markers, including TNF-α, IL-1β, and IL-6, in the serum and colon tissues. Additionally, APE treatment reduced the levels of TLR4 and phosphorylation of p-NF-κB and p-IK-Kβ. The main components of APE are taxifolin, 3,5-dihydroxy-2-(4-hydroxyphenyl)-7-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] oxychromen-4-one, hyperoside, rutin, kaempferol, isorhamnetin, 7,8-dihydroxyflavone, and kaempferide.Conclusions: To the best of our knowledge, the present study is first to demonstrate that APE exerts a protective effect against intestinal inflammation in UC by affecting TLR4-dependent NF-κB signaling pathways.

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Study on the mechanism of Indigo naturalis and its two main compounds (indigo and indirubin) in the treatment of ulcerative colitis based on TLR4/MyD88/NF-κB pathway and intestinal microorganisms

10.21203/rs.3.rs-31454/v1 ◽

2020 ◽

Author(s):

Qi-yue Yang ◽

Ya-nan He ◽

Le-le Ma ◽

Run-chun Xu ◽

Nan Li ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Activity Index ◽

Disease Activity Index ◽

Pathological Section ◽

Inflammatory Cytokine Production ◽

Tnf Α ◽

Indigo Naturalis ◽

Inflammation Cytokines

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB，TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.

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

10.21203/rs.3.rs-17639/v1 ◽

2020 ◽

Author(s):

Guangmeng Xu ◽

Yajuan Sun ◽

Huaiqiang He ◽

Qiuli Xue ◽

Yajie Liu ◽

...

Keyword(s):

Intestinal Inflammation ◽

Activity Index ◽

Damage Index ◽

Interleukin 4 ◽

Inflammatory Factors ◽

Control Group ◽

Group Model ◽

Enterocyte Apoptosis ◽

Tnf Α ◽

Protein Expressions

Abstract 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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Bu-Zhong-Yi-Qi Granule Enhances Colonic Tight Junction Integrity via TLR4/NF-κB/MLCK Signaling Pathway in Ulcerative Colitis Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6657141 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Xiuhong Kang ◽

Mengdi Jia ◽

Luqing Zhao ◽

Shengsheng Zhang

Keyword(s):

Ulcerative Colitis ◽

Tight Junction ◽

Western Blot ◽

Activity Index ◽

Damage Index ◽

Interleukin 10 ◽

Trinitrobenzene Sulfonic Acid ◽

Therapeutic Effects ◽

Mrna Levels ◽

Tnf Α

Background. Bu-zhong-yi-qi granule (BZYQ), a sort of Chinese herbal medicine, has exhibited therapeutic effects on ulcerative colitis (UC). However, the mechanism of BZYQ has not been fully clarified. This study was aimed at investigating the effects of BZYQ on UC rats model and at exploring its potential mechanism. Methods. The UC rats were established by enema of trinitrobenzene sulfonic acid (TNBS). The therapeutic effects of BZYQ treatment were evaluated by disease activity index (DAI), colon macroscopic damage index (CMDI) scores, and histological observation. The mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were measured by quantitative real time-polymerase chain reaction (qPCR). The expression of tight junction (TJ) proteins, occludin and claudin-1, in the colon was determined by Western blot and immunofluorescence. The expression of toll-like receptors 4 (TLR4), nuclear factor-kappa B (NF-κB), p-NF-κB, myosin light chain kinase (MLCK), MLC, and p-MLC levels in colon was determined by Western blot or qPCR. Results. The results showed that BZYQ could attenuate DAI, CMDI, and histological inflammation. TJ proteins expression was decreased in UC rats, but treatment with BZYQ restored the expression of occludin and claudin-1. In addition, BZYQ administration ameliorated UC-associated increase in the production of TNF-α, IL-1β, and the expression of TLR4, NF-κB, p-NF-κB, MLCK, MLC, and p-MLC, while BZYQ administration increased the production of IL-10. Conclusions. The therapeutic effect of BZYQ on UC is at least partially through regulation of the secretion of some inflammatory cytokines and improvement of TJ integrity via TLR4/NF-κB/MLCK pathway.

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Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

Canadian Journal of Gastroenterology ◽

10.1155/1990/314931 ◽

1990 ◽

Vol 4 (7) ◽

pp. 468-471 ◽

Cited By ~ 3

Author(s):

MG Robinson ◽

DL Decktor

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

First Episode ◽

High Dose ◽

Aminosalicylic Acid ◽

Open Label ◽

Distal Ulcerative Colitis ◽

The Mean

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

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Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways

BioMed Research International ◽

10.1155/2021/5561221 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xinghan Zheng ◽

Liting Mai ◽

Tongtong Wang ◽

Ying Xu ◽

Zireng Su ◽

...

Keyword(s):

Signaling Pathways ◽

Activity Index ◽

Disease Activity Index ◽

Protective Effects ◽

Intestinal Epithelial ◽

Colon Tissue ◽

Epithelial Barrier Function ◽

Brucea Javanica ◽

Tnf Α ◽

Brucea Javanica Oil

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

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Morphological aspects of the protective effect of newly formulated rectal suppositories with turmeric extract in experimental Crohn’s disease

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2021.02.67-77 ◽

2021 ◽

pp. 67-77

Author(s):

М.В. Осиков ◽

Е.В. Симонян ◽

А.Е. Бакеева ◽

Л.В. Астахова

Keyword(s):

Tissue Damage ◽

Activity Index ◽

Curcuma Longa ◽

Clinical Status ◽

Damage Index ◽

Disease Activity Index ◽

The Novel ◽

Turmeric Extract ◽

Tnf Α ◽

Rectal Suppositories

Введение. Востребованным для лечения болезни Крона (БК) является разработка новых, обоснованных с патогенетических позиций и безопасных лекарственных средств преимущественно локального действия эндогенного или растительного происхождения. В этом отношении привлекает внимание экстракт корневищ Куркумы длинной (Curcuma longa), содержащий куркуминоидный комплекс, обладающий плейотропными эффектами. Ранее нами показано, что экстракт куркумы в составе суппозиториев при экспериментальной БК обладaет иммуномодулирующим и местным антиоксидантным действием, что предполагает влияние экстракта куркумы на морфологию очага повреждения в кишечнике при БК. Цель работы - изучение влияния экстракта куркумы в составе оригинальных ректальных суппозиториев на динамику морфологических изменений, экспрессию миелопероксидазы (МПО) и TNF-a в очаге повреждения толстого кишечника при экспериментальной БК. Методика. Эксперимент выполнен на 49 половозрелых крысах-самцах Wistar. БК моделировали введением per rectum спиртового раствора тринитробензосульфоновой кислоты (ТНБС). Оригинальные ректальные суппозитории массой 300 мг на основе полиэтиленгликолей различной молекулярной массы, содержащие 0,075 мг куркумина из экстракта корневищ Curcuma longa L., вводили per rectum каждые 12 ч в течение 7 сут. Клинический статус оценивали по модифицированной шкале Disease activity index (DAI). Морфометрически в стенке кишечника оценивали размер язвенного дефект, выраженность клеточной инфильтрации, рассчитывали индекс тканевого повреждения (tissue damage index, TDI), оценивали экспрессию МПО и TNF-α. Результаты. При экспериментальной БК на 3-и, 5-е и 7-е сут наблюдения в толстом кишечнике обнаруживались язвенные дефекты, выраженный отек тканей, плотная нейтрофильно-лимфоцитарная инифильтрации с примесью эозинофилов, плазмоцитов, гистиоцитов, фибробластов, наблюдалось формирование грануляционной ткани. Индекс тканевого повреждения возрастал, повышалась экспрессия МПО и TNF-α. Размер язвенных дефектов, выраженность инфильтрации, индекс тканевого повреждения соответствовали клинической картине и индексу DAI. Применение оригинальных ректальных суппозиториев с экстрактом куркумы (0,075 мг) приводит к снижению выраженности клинических и морфологических признаков заболевания, максимальный эффект отмечен на 5-е и 7-е сут наблюдения. Заключение. Установленные протекторные свойства куркумина в составе оригинальных ректальных суппозиториев при БК на доклиническом этапе расширяют современные представления о плейотропных эффектах экстракта куркумы и являются предпосылкой для проведения дальнейших исследований и внедрения новой лекарственной формы в клиническую практику. The development of safe, new, pathogenetically justified medicines, mainly with local effects and of endogenous or plant origin, is of great interest for treatment of Crohn’s disease (CD). In this regard, an extract of rhizomes of Curcuma longa, containing a curcuminoid complex with pleiotropic effects, has attracted attention. We showed previously that having turmeric extract in suppositories for treatment of experimental CD would produce immunomodulatory and antioxidant effects. This suggests that turmeric extract affects the morphology of the CD intestinal lesion. The aim of this work was to study the effect of turmeric extract in the composition of novel rectal suppositories on the morphology and expression of myeloperoxidase (MPO) and TNF- α in colon lesions of experimental CD. Methods. Experiments were performed on 49 sexually mature male Wistar rats. CD was modeled by administration per rectum of an alcohol solution of trinitrobenzenesulfonic acid. The newly formulated rectal suppositories weighing 300 mg and based on polyethylene glycols of various molecular weights and containing 0.075 mg of curcumin obtained from Curcuma longa L. rhizome extract were administered per rectum every 12 hours for 7 days. The clinical status was assessed with the modified disease activity index (DAI) scale. The ulcer defect diameter, cell infiltration, tissue damage index (TDI), MPO expression, and TNF-α expression were evaluated. Results. In experimental CD on the 3rd, 5th, and 7th days of observation, a morphometric assessment of the lesion in the large intestine revealed the presence of ulcerative defects, edema, thick neutrophilic lymphocytic infiltration with an admixture of eosinophils, plasmocytes, histiocytes, fibroblasts, the formation of granulation tissue, increased TDI, and increased expression of MPO and TNF-α. The size of ulcerative defects, the degree of wall infiltration by neutrophils, lymphocytes, plasmocytes, histiocytes, and fibroblasts were recorded. The TDI, the expression of MPO, and TNF-α were associated with the DAI. The use of the novel rectal suppositories produced a maximal effect on the 5th and 7th days of observation. The severity of clinical and morphological signs of the disease were reduced. These signs included ulcer size, TDI, intestinal wall infiltration with neutrophils, lymphocytes, eosinophils, plasmocytes, histiocytes, and fibroblasts, and expression of MPO and TNF-α. Conclusion. The results supplement available data on the pathogenesis, the role of the expression of MPO and TNF-α, and the morphology of the lesion in the clinical status in TNBS-induced CD in rats. The demonstrated, protective properties of curcumin in the composition of the novel rectal suppositories at the preclinical stage of CD expand modern understanding of the pleiotropic effects of turmeric extract and are a prerequisite for further research and the introduction of a new dosage form in clinical practice.

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Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽

10.1055/a-1506-3476 ◽

2021 ◽

Author(s):

Jiaqi Wu ◽

Yuzheng Wu ◽

Yue Chen ◽

Mengyang Liu ◽

Haiyang Yu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Activity Index ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Function Evaluation ◽

Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

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P187 The significance of netrin-1 level in the clinical activity of ulcerative colitis, its association between TNF-α and IL-6

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.316 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S232-S232

Author(s):

H Korkmaz ◽

K Fidan

Keyword(s):

Ulcerative Colitis ◽

Proinflammatory Cytokines ◽

Activity Index ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Clinical Activity ◽

Tnf Α ◽

Significant Difference ◽

And Control ◽

Control Study

Abstract Background In this study, we investigated the importance of netrin-1 levels in ulcerative colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-α. Methods This study is a type of case–control study. Sixty-seven patients with UC (36 of them activation, 31 of remission) and 50 healthy controls were included in the study. UC patients; ‘Truelove Witts clinical activity index by remission (n = 31), mild activation (n = 21), moderate activation (n = 6) and severe activation (n = 9) were divided into groups. Netrin, IL-6 and TNF-α measurements in plasma samples were performed using enzyme-linked immunosorbent assay kit. Results Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-α, neutrophil, platelet (p < 0.05 for all). The plasma netrin-1 mean of UC with severe activation group (139.21 ± 48.09 pg/ml) was statistically significantly higher than that of the mild activation (p = 0,037), remission group (p = 0,001) and control group(p = 0,011). The plasma netrin-1 mean of UC with moderate activation group was statistically significantly higher than that of the mild activation(p = 0,045) and remission group(p = 0,004). Conclusion Our results reveal that plasma netrin-1 levels have been shown to be associated with UC activation, similar to proinflammatory cytokines such as TNF-α and IL-6, in UC.

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The serotonin reuptake transporter is reduced in the epithelium of active Crohn’s disease and ulcerative colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00244.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. G761-G768

Author(s):

Jonas Woll Jørandli ◽

Silje Thorsvik ◽

Helene Kolstad Skovdahl ◽

Benedikt Kornfeld ◽

Siri Sæterstad ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Intestinal Epithelium ◽

Serotonin Reuptake ◽

Tryptophan Hydroxylase ◽

Intestinal Inflammation ◽

Serotonin Synthesis ◽

Crohn’S Colitis ◽

Tnf Α ◽

Serotonin Reuptake Transporter

The serotonin reuptake transporter is potently reduced in inflamed areas of Crohn’s ileitis, Crohn’s colitis, and ulcerative colitis. The changes are localized to the intestinal epithelium and can be induced by TNF-α. The serotonin synthesis through tryptophan hydroxylase 1 is unchanged. This regulation is suggested as a mechanism underlying the increased extracellular serotonin levels associated with intestinal inflammation.

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Huangkui Lianchang Decoction Ameliorates DSS-Induced Ulcerative Colitis in Mice by Inhibiting the NF-kappaB Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1040847 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Zongqi He ◽

Qing Zhou ◽

Ke Wen ◽

Bensheng Wu ◽

Xueliang Sun ◽

...

Keyword(s):

Ulcerative Colitis ◽

Western Blot ◽

Signaling Pathway ◽

Intestinal Inflammation ◽

Activity Index ◽

Quantitative Polymerase Chain Reaction ◽

Comparable Efficacy ◽

Intestinal Damage ◽

Macroscopic Lesion ◽

Cox 2

Background. The nuclear factor kappa beta (NF-κB) signaling pathway plays an important role in ulcerative colitis (UC). Huangkui Lianchang decoction (HLD) is an effective traditional Chinese medicinal compound used in the treatment of UC. HLD has good effects in the clinic, but the mechanism by which HLD acts is unclear. This study aims to reveal the exact molecular mechanism of HLD in the treatment of UC. Methods. Mouse ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with HLD. Intestinal damage was assessed by disease activity index (DAI), colon macroscopic lesion scores, and histological scores. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were detected in colon tissue using ELISA. Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities in the colonic mucosa were measured. The levels of IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). The expression of NF-κB, IκBα, and p-IκBα in the colon was measured by Western blot. Results. After treatment with HLD, the DAI scores, macroscopic lesion scores, and histological scores decreased, and the levels of inflammatory cytokines related to the NF-κB signaling pathway, such as IL-6, TNF-α, and IL-1β, as well as those of iNOS and COX-2, were reduced; at the same time, colonic pathological damage was alleviated, and the MPO and SOD activities decreased. Western blot confirmed that HLD can inhibit the NF-κB signaling pathway in DSS-induced ulcerative colitis. Conclusion. HLD can alleviate the inflammation caused by ulcerative colitis. In particular, high doses of HLD can significantly alleviate intestinal inflammation and have comparable efficacy to Mesalazine. We propose that the anti-inflammatory activity of HLD on DSS-induced colitis in mice may involve the inhibition of the NF-κB pathway.

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