Changes In Colon Tissue Research Articles

Mechanism of Shenling Baizhu Powder on treatment of ulcerative colitis based on NLRP3 inflammatory

This study deciphered the mechanism of Shenling Baizhu Powder in treatment of mouse model of ulcerative colitis(UC) via NOD-like receptor thermoprotein domain 3(NLRP3) signaling pathway. After three days of adaptive feeding, 70 SPF-grade BALB/c mice were randomized into 7 groups: normal group, model group(dextran sodium sulfate, DSS), mesalazine group(DSS + 5-aminosalicylic acid, 5-ASA), NLRP3 inhibitor group(DSS + MCC950), and high-, medium-, and low-dose Shenling Baizhu Powder groups(DSS + high-, medium-, and low-dose Shenling Baizhu Powder), with 10 mice per group. The normal group had free access to double distilled water, and the remaining groups had free access to DSS-containing water to establish the acute UC model. Intragastric administration was started at the same time as modeling for one week. During the experiment, the general mental state and disease activity of each group of mice were recorded and scored. After the experiment, colon and serum samples were collected. The pathological changes in colon tissue were observed through hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of interleukin-18(IL-18) and myeloperoxidase(MPO) in colon tissue and interleukin-1β(IL-1β) in serum. Immunofluorescence(IF) and immunohistochemistry(IHC) methods were employed to examine the expression of NLRP3 and IL-18 in colon tissue. Western blot was employed to measure the protein levels of NLRP3, apoptosis-associated speck-like protein(ASC), cystein-aspartate protease 1(caspase-1), and downstream inflammatory cytokines in colon tissue. Compared with the normal group, the modeling of UC increased the disease activity index(DAI), colon pathological injury score, IL-1β level in serum, and IL-18 and MPO levels in colon tissue(P<0.05, P<0.01). Furthermore, the modeling caused obvious pathological changes and up-regulated the expression of NLRP3, caspase-1, ASC, pro-IL-1β, cleaved-IL-1β, pro-IL-18, and cleaved-IL-18 in the colon(P<0.01). Compared with the model group, the administration of corresponding drugs decreased the DAI, pathological injury score, IL-1β level in serum, and IL-18 and MPO levels in colon tissue, and down-regulated the protein levels of NLRP3, caspase-1, ASC, pro-IL-1β, cleaved-IL-1β, pro-IL-18, and cleaved-IL-18 in the colon(P<0.05, P<0.01). According to the results of previous study and this study, we concluded that Shenling Baizhu Powder can alleviate the inflammatory response and intestinal damage of DSS-induced UC by regulating the expression of the proteins and inflammatory cytokines associated with NLRP3 signaling pathway.

Ferulic acid relieved ulcerative colitis by inhibiting the TXNIP/NLRP3 pathway in rats.

Ulcerative colitis (UC) is a disorder of the bowel that is characterized by a chronic inflammatory response. The traditional Chinese herbal medicine ferulic acid (FA) is known for its antioxidant, antiapoptotic, and antiinflammatory properties. However, its role in UC is still unclear. Thus, the current study was conducted to investigate the role of FA in UC. Rats were treated with 2,4,6-triabrobenzene sulfonic acid to induce UC and subjected to FA. Human intestinal microvascular endothelial cells (HIMECs) were treated with tumor necrosis factor-α (TNF-α) and pretreated with FA. Pathological changes in colonic tissues were visualized via hematoxylin-eosin staining. Enzyme linked immunosorbent assay was conducted to detect interleukin (IL)-6, IL-12, and IL-1β levels. Cell morphology was visualized by using a microscope, and viability was detected by using MTT. The percentage of apoptosis was detected via flow cytometry. Western blot analysis was performed to detect the expression of the apoptosis-related proteins thioredoxin-interacting protein (TXNIP) and NOD-like receptor pyrin domain-containing 3 (NLRP3). In vivo FA administration alleviated intestinal injury in UC rats and inhibited inflammatory factor levels (IL-6, IL-12, and IL-1β), apoptosis-related protein expression (caspase-1 and caspase-3) and the TXNIP/NLRP3 signaling pathway. In vitro, TNF-α treatment reduced HIMEC viability, increased cell apoptosis and inflammatory factor levels and activated the TXNIP/NLRP3 signaling pathway. However, FA treatment restored the viability of HIMECs, reduced TNF-α-induced cell apoptosis and inflammation and inhibited the TXNIP/NLRP3 signaling pathway. Furthermore, with increasing FA concentration, the effects were stronger. In summary, FA inhibits the inflammatory injury of endothelial cells in ulcerative colitis or alleviates TNF-α-induced HIMEC injury by inhibiting the TXNIP/NLRP3 signaling pathway.

Reduce the Changes in Histological Features of Colon Resulting from Induced Ulcerative Colitis in Mice by Worm Antigens.

Ulcerative colitis is one of the inflammatory bowel disease (IBD) consequences characterized by chronic inflammation of the gastrointestinal (GI) tract. The current study aims to determine the changes in colon tissue caused by induced Ulcerative Colitis and reduce these changes by worms' antigen. The study included 45 adult male albino mice (Mus musculus), with ages ranging between 8-10 weeks; the average weights ranged between 18-32 g. Ulcerative colitis was induced by intracolonic administration of 100 μL of 4% after they had been starved for 18 h. The animals were dissected after one week, and routine histological sections were conducted. The results of the histological study showed that in the colon of white mice treated with 4% acetic acid occurred, many histological changes were represented by the appearance of inflammatory cells in the mucous layer around the goblet cells, and the formation of vacuoles, necrosis at epithelium and intense congestion under the surface epithelium. The marked histological sections of the colon in mice with induced ulcerative colitis treated with helminth extract at a concentration of 0.1 mg/kg for a week, were showed that the histological changes began to decrease in the colon tissue, with the presence of a few inflammatory cells as well as little mucus secretion.

Potential molecular mechanism of Guiqi Baizhu Decoction in radiation-induced intestinal edema by regulating HIF-1a, AQP4 and Na+/K+-ATPase

Guiqi Baizhu Decoction (GQBZD) has a good protective effect on radiation-induced intestinal edema (RIIE). However, the underlying molecular mechanisms need further elucidation. To reveal the potential mechanism of RIIE and GQBZD treatment. SD rats were irradiated with 6Gy X-ray to establish RIIE model. The general condition of the rats was observed; the dry/wet weight ratio of colon tissue was detected; the morphological changes of colon tissue were observed by HE staining; the expressions of ROS, HIF-1α and AQP4 in colon tissue were detected by confocal laser scanning; the expression of edema-related proteins was detected by Western blot. In addition, human colon epithelial cells (NCM460) was irradiated with 2Gy X-ray, and HIF-1α expression in NCM460 was knocked down by small interfering RNA (siRNA) transfection, and the activity of Na+/K+-ATPase was detected by enzyme activity kit; the ROS expression was detected by flow cytometer; the AQP4 expression was detected by laser confocal microscopy; and the expression of edema-related proteins were detected by Western blot. We found that after irradiation, the colon tissue of rats was significantly edema, mainly manifested as mucosal and submucosal edema, and the ultrastructure was reflected in the structural damage of nucleus and mitochondria. ROS, HIF-1α and AQP4 were significantly expressed, and Na+/K+-ATPase expression/activity was decreased. After the intervention of GQBZD, the edema of the colon tissue of the rats was improved, the expressions of ROS, HIF-1α and AQP4 were decreased, and the expression/activity of Na+/K+-ATPase was increased. Ionizing radiation (IR) can cause significant intestinal edema. AQP4 and Na+/K+-ATPase are the key factors of RIIE, which are regulated by ROS and HIF-1α. GQBZD can improve hypoxia and oxidative stress, regulate the expression of AQP4 and Na+/K+-ATPase, and achieve a protective effect on RIIE. This study is the first to reveal the mechanism of RIIE.

Effect mechanism of blistering moxibustion on visceral hypersensitivity of irritable bowel syndrome in mice based on 5-HT signal pathway

To observe the effect of blistering moxibustion on the expression levels of 5-hydroxytyptamine (5-HT) and its receptors of the colon tissue in the mice with visceral hypersensitivity of irritable bowel syndrome (IBS), so as to explore the effect mechanism of blistering moxibustion in treatment of IBS. Forty SPF-grade newborn Kunming mice were randomly divided into a normal group, a model group, an antagonist group and a blistering moxibustion group, 10 mice in each one. Before modeling, the injection with 0.2 mL parachlorophenylalanine (PCPA) was given on the lateral ventricle in the antagonist group. The endorectal glacial acetic acid stimulation combined with tail clipping was used to prepare the model of visceral hypersensitivity of IBS in the model group, the antagonist group and the blistering moxibustion group. After modeling, in the blistering moxibustion group, the intervention with blistering moxibustion was exerted at "Zhongwan" (CV 12), "Tianshu" (ST 25) and "Zusanli" (ST 36), once herbal irritant plaster at each acupoint, for 2 h each time, once a week, consecutively for 3 weeks. Abdominal withdrawal reflex (AWR) score and electromyographic (EMG) amplitude of abdominal muscles were adopted to evaluate the visceral hypersensitivity. HE staining was applied to observe the morphological changes in colon tissue, and immunohistochemistry was to determine the expression levels of 5-HT and its receptors. Compared with the normal group, EMG amplitude of abdominal muscles was increased under 20, 40 mm Hg (1 mm Hg=0.133 kPa) in the model group (P<0.05), AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all increased in the model group (P<0.05). In comparison with the model group, EMG amplitude of abdominal muscles was reduced under 20 mm Hg in the blistering moxibustion group (P<0.05), AWR scores were increased under 40 mm Hg in both the blistering moxibustion group and the antagonist group (P<0.05); AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all reduced in both the blistering moxibustion group and the antagonist group (P<0.05). Compared with the normal group, in the model group, the mucosa was slightly disturbed, while, the moderate inflammatory cells were visible in the submucosa. In comparison with the model group, the inherent glands of mucosa were regular in shape and a small number of inflammatory cells were visible in both the blistering moxibustion group and the antagonist group. In comparison with the normal group, the average positive staining area percentage (APSAP) of 5-HT and 5-HT3R of the colon tissue was increased, while, APSAP of 5-HT4R was reduced in the model group (P<0.05). Compared with the model group, APSAP of 5-HT and 5-HT3R was reduced in both the blistering moxibustion group and the antagonist group (P<0.05). Blistering moxibustion can relieve the visceral hypersensitivity of the mice with visceral hypersensitive IBS and the underlying mechanism is related to the regulation of the gut-brain axis mediated by 5-HT signaling pathway.

Mechanism of Huanglian Houpo Decoction in treatment of ulcerative colitis in mice based on brain-gut axis

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1β, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.

Antioxidative mechanisms and anticolitic potential of Desmodium styracifolium (Osb.) Merr. in DSS-induced colitic mice

• Desmodium styracifolium extract had flavonoids as the potent antioxidants. • The herb extract reduced oxidative stress via hydrogen atom transfer pathway. • The treatment also reduced the inflammatory markers of the colonic tissues. • Anticolitic effect of the herb extract was due to the low oxidative stress. This study aimed to determine the anticolitic effect of Desmodium styracifolium (DS) extract in ulcerative colitis (UC) mice and its possible antioxidative mechanisms. Phenolic antioxidants and free radical scavenging activities of the herb extract were determined. LCMS was used to identify phenolic compounds in the herbal extract. Ulcerative colitis in C57BL/6 SPF mice was induced with dextran sodium sulfate (DSS). The mice were treated with two doses of the DS extract during the 7-day experiment. Colon length, spleen weight, histopathological changes in colonic tissues, and disease activity index (DAI) of the mice were measured. The bioactive antioxidants in DS extract were flavonoids. The DS extract-treated UC mice had a lower DAI than the untreated UC mice. Also, the herbal treatment had downregulated expressions of proinflammatory cytokine genes in the colonic tissues of the mice compared to the control. Therefore, it is a potent anti-inflammatory agent for reducing UC symptoms.

Polysaccharides from Panax ginseng C. A. Meyer alleviated DSS-induced IBD by inhibiting JAK2/STAT1/NLPR3 inflammasome signalling pathway in mice

Panax ginseng polysaccharides (GPS) are isolated from Panax ginseng C. A. Meyer, which has many pharmacological activities. However, although the protective effect of GPS on inflammatory bowel disease (IBD) has been characterized, its mechanism has not yet been fully elucidated. In the present study, we clarified it effect on IBD in mice and studied the mechanism of reducing inflammation. IBD model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 days. Our results showed that GPS treatment significantly relieved disease activity index, colon length shortening and pathological changes in colonic tissue. Furthermore, GPS treatment significantly reduced oxidative stress and inflammatory cytokines in the colonic tissue via inhibiting JAK2/STAT1/NLRP3 inflammasome signalling pathway. In conclusion, these results demonstrated that GPS could attenuate inflammatory response via inhibiting JAK2/STAT1/NLPR3 inflammasome signalling pathway. Hence, GPS may be a potential natural medicine to inhibit JAK2/STAT1/NLRP3 inflammasome signalling pathway and reduce inflammation in IBD.

Short-term treatment with zingerone ameliorates dextran sulfate sodium-induced mouse experimental colitis.

Ulcerative colitis (UC) is a relapsing and chronic inflammatory disease of the gastrointestinal tract, which seriously threatens human health. Zingerone (ZO) has been proven to be effective for many diseases. The purpose of this study is to investigate the protective effects and potential mechanisms of ZO extracted from ginger on dextran sulfate sodium (DSS)-induced mouse ulcerative colitis (UC). The results showed that ZO alleviated the weight loss of UC model mice, reduced the disease activity index scores, and inhibited the shortening of colon length. ZO also improved DSS-induced pathological changes in colon tissue and inhibited the secretion of pro-inflammatory cytokines in colon and mesenteric lymph nodes. Further mechanism analysis found that ZO inhibited DSS-induced nuclear factor-κB pathway activation, and regulated peroxisome proliferator-activated receptor γ (PPARγ) expression. To further explore whether PPARγ was involved in the anti-UC effect of ZO, PPARγ inhibitor GW9662 was used. Although ZO also showed a protective effect on GW9662-treated colitis mice, the protective role was significantly weakened. Importantly, the administration of GW9662 significantly aggravated UC compared with the ZO + DSS group. In addition, we preliminarily found that ZO had the effects of inhibiting DSS-induced oxidative stress, maintaining intestinal barrier, and inhibiting the content of LPS and the population of Escherichia coli. These results indicated that supplementation with ZO might be a new dietary strategy for the treatment of UC. © 2022 Society of Chemical Industry.

Copper oxide nanoparticles synthesized from Trichosanthes kirilowii ameliorates the DSS-induced acute colitis in mice through the suppression of inflammatory responses

IntroductionUlcerative colitis (UC) is chronic inflammatory ailment that distinguished by diarrhea, stomach pain, reduced body weight, and hematochezia. UC affects nearly 400 per 100,000 peoples worldwide. In this exploration, we intended to fabricate the copper oxide nanoparticles from the T. kirilowii (TK-CuNPs) and inspect their curative potential against the Dextran sulfate disodium salt (DSS)-provoked colitis in animals. MethodsFormulated TK-CuNPs were characterized by UV–vis spectroscopy, FT-IR, SEM, TEM, and DLS techniques. UC was provoked in mice through administering of 2% DSS for 7-days and treated with the 10 mg/kg bodyweight of TK-CuNPs via intragastric intubation. Myeloperoxidase activity, colon weight, and length, and spleen weight were determined by standard methods. Pro-inflammatory mediators, i.e. IL-6, IL-1β, and TNF-α were inspected by the assay kits. The expression of COX-2 and iNOS were analyzed by immunohistochemistry. Histopathological changes in colon tissues were investigated microscopically by H&E staining. The cytotoxicity and in vitro anti-inflammatory activities of TK-CuNPs were analyzed in RAW-264.7 cells. ResultsThe outcomes of various characterization studies demonstrated the formation of TK-CuNPs. The TK-CuNPs supplementation to the DSS induced colitis mice demonstrated the appreciable bodyweight gain and reduced the DAI scores. TK-CuNPs improved the colon length and spleen weight and suppressed the MPO activity. The status of pro-inflammatory mediators IL-6, IL-1β, and TNF-α was appreciably suppressed by the TK-CuNPs treatment. The expressions of COX-2 and iNOS was also diminished by the TK-CuNPs. TK-CuNPs did not possessed toxicity to the RAW-264.7 cells and suppressed the inflammatory markers level in the RAW-264.7 cells. Discussion and ConclusionThe current findings revealed that fabricated TK-CuNPs can be a hopeful therapeutic agent to treat acute colitis.

Effects of astragaloside Ⅳ on inflammatory response and percentage of peripheral blood Th17 cells in mice with ulcerative colitis

This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-β, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-β, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.

Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation.

BackgroundPrevious studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood.ObjectivesWe aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action.MethodsHemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model.ResultsIn Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model.ConclusionsWe demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

Ultrasonic and Microwave Co-Extraction Optimization of Polysaccharide of Portulaca oleracea L. Technology and its Effect on Ulcerative Colitis

The extraction conditions of polysaccharides from Portulaca oleracea L.（POP） were optimized and its effects on the colonic mucosa of mice with ulcerative colitis were studied. In this study, POP were extracted by ultrasonic and microwave synergism. The extraction process of POP was optimized by a single factor experiment and orthogonal design. HE staining was used to evaluate the pathological changes of colon tissues in mice. The results showed that the optimal extraction conditions were as follows: extraction time was 550 s, microwave power was 40 W, solid-liquid ratio (W/V) was 1:35, and extraction times were 3. Under these conditions, the extraction rate of POP was 3.80%. POP could improve the disease state of UC mice, and the high dose group could significantly reduce the DAI index. The results of the HE experiment showed that POP could reduce inflammatory infiltration and tissue damage of the colon in UC mice. This study provided a theoretical basis for the preparation of POP and its clinical application in the treatment of ulcerative colitis.

Lactobacillus fermentum ZS40 Ameliorates Inflammation in Mice With Ulcerative Colitis Induced by Dextran Sulfate Sodium.

Ulcerative colitis is an inflammatory disease of the intestine caused by many reasons, and it may even develop into colon cancer. Probiotics are normal bacteria that exist in the human body and have been proven to regulate the balance of intestinal flora and alleviate inflammation. The current study aimed to study the effect of Lactobacillus fermentum ZS40 (ZS40) on dextran sulfate sodium (DSS)-induced ulcerative colitis mice. The length and weight of the colon were measured, and the histopathological morphological changes of colon tissue were observed to evaluate the effects of ZS40 on colitis. Biochemical kits, ELISA kits, real-time quantitative PCR (RT-qPCR), and western blot were also used to detect the effects of ZS40 on serum and colon tissue related oxidative indicators and pro-inflammatory and anti-inflammatory cytokines. We found that ZS40 could reduce colonic inflammatory cell infiltration and goblet cell necrosis, increase total superoxide dismutase and catalase in mouse serum, and reduce myeloperoxidase and malondialdehyde levels. ZS40 could down-regulate the level of proinflammatory cytokines and up-regulate the level of anti-inflammatory cytokines. More importantly, ZS40 down-regulated the relative expression of nuclear factor-κB p65 (NF-κBp65), IL-6, and TNF-α mRNA and protein, up-regulated the relative expression of inhibitor kapa B alpha (IκB-α). By regulating the NF-κB and MAPK pathways to down-regulated the relative expression of p38 and JNK1/2 mRNA and p38, p-p38, JNK1/2, and p-JNK1/2 proteins. Our study suggested that ZS40 may serve as a potential therapeutical strategy for ulcerative colitis.

Jiawei Baitouweng Decoction affects intestinal mucosal tight junction proteins in rats with ulcerative colitis through p38 MAPK-MLCK signaling pathway

The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.

Exploring the Mechanism of Berberine Intervention in Ulcerative Colitis from the Perspective of Inflammation and Immunity Based on Systemic Pharmacology.

Background Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Recent studies found that berberine had effects on inflammatory diseases and immune diseases. Methods The PharmMapper database was used to predict the berberine potential target and GeneCards database and OMIM database were utilized to collect UC genes. The Cytoscape software was used to construct and analyze the networks and DAVID was utilized to perform enrichment analysis. Then, animal experiments were performed to validate the prediction results. The experimental rats were randomly divided into normal group (control group), model group, and berberine group. The general condition, body weight, gross morphology of colon tissue, and colonic mucosal damage index (CMDI) score were observed. The pathological changes of colon tissue were observed by H&E staining. The levels of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-4 were detected by ELISA. The expressions of IL-1β, TNF-α, and IL-4 protein in colon tissue were detected by immunohistochemistry. Results A total of 211 Berberine's potential targets and 210 UC genes were obtained. The enrichment analysis showed that berberine may regulate inflammation, inflammatory cytokines, and their mediated inflammation signal pathways such as inflammatory bowel disease (IBD), rheumatoid arthritis, cytokine-cytokine receptor interaction, TNF, T cell receptor, Toll-like receptor, and JAK/STAT signaling pathway. Compared with the model group, the body mass of rats in the berberine group was significantly increased (P < 0.05); the general morphology and pathological changes of colon tissue were significantly improved; CMDI score, serum and colon tissue IL-1β, TNF-α content, and protein expression were decreased significantly (P < 0.05); and IL-4 content and protein expression increased significantly (P < 0.05). Conclusion Berberine can interfere with UC through related biological processes and signal pathways related to inflammation and immunity. In-depth exploration of the mechanism of berberine in the treatment of UC will provide a basis for clinical application.

Yu Shi An Chang Fang Ameliorates TNBS-Induced Colitis in Mice by Reducing Inflammatory Response and Protecting the Intestinal Mucosal Barrier.

Ulcerative colitis (UC) is an inflammatory bowel disease that is related to the occurrence of colon cancer. This study aimed to investigate the underlying mechanism by which Yu Shi An Chang Fang (YST) treated UC. 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) was used to construct the UC model. The body weight, fecal viscosity, and fecal bleeding of all mice were recorded every day to calculate the DAI value. The pathological changes in colon tissues were observed by hematoxylin-eosin (H&E) staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and myeloperoxidase (MPO) reflecting inflammation and the levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) reflecting oxidative stress in colon tissues were all measured by their assay kits. The mRNA expression of TNF-α, IL-1β, and IL-6 in colon tissues was detected by quantitative reverse transcription-PCR (qRT-PCR). The expression of proteins related to pyroptosis and the colonic mucosal barrier was analyzed by Western blot. As a result, TNBS caused decreases in body weight and colon lengths, triggered serious histological damage, promoted inflammation, oxidative stress, and pyroptosis, and destroyed the colonic mucosal barrier. The above changes caused by TNBS in colitis mice could be partially reversed by YST. In conclusion, YST ameliorates TNBS-induced UC in mice by reducing the inflammatory response and protecting the intestinal mucosal barrier.

Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn's Disease Model: Time- and Molar Mass-Dependent Effects.

Background: The incidence of Crohn’s disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient’s lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (colitis) in the early stages of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD in an animal model. Methods: Sprague–Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively. Results: Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of colitis. Conclusions: Dietary oat beta-glucans can reduce colitis at the molecular and organ level and accelerate CD remission.

Baitouweng Decoction Ameliorates Ulcerative Colitis in Mice Partially Attributed to Regulating Th17/Treg Balance and Restoring Intestinal Epithelial Barrier.

Ulcerative colitis (UC) is a chronic intestinal disease with unclear pathogenesis. With an increasing global prevalence over the past two decades, UC poses a serious threat to public health. Baitouweng decoction (BTW), a traditional Chinese medicine, has been shown to have good clinical efficacy for treating intestinal inflammation. Yet, the efficacy of BTW in UC and the underlying mechanism remain unclear. The current study aimed to determine whether BTW suppressed intestinal inflammation in mice and the potential mechanism. We used a dextran sulfate sodium (DSS)-induced murine colitis model to test the anti-inflammatory efficacy of BTW. Clinical symptoms were scored by the disease activity index (DAI), and the colon length and pathological changes in colon tissue were also used to further evaluate the efficacy of BTW. Precisely how BTW affected immune function and the intestinal barrier of UC mice was also examined. BTW significantly reduced DAI score and colonic pathological damage. BTW regulated the balance between T helper (Th)17 and regulatory T (Treg) cells, decreased interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, and increased IL-10 levels. BTW reduced intestinal permeability of UC mice, increased expression of tight junction proteins (occludin and zonula occludens-1), and decreased expression of phospho-nuclear factor (p-NF)-κB and phospho-extracellular signal-regulated kinase (p-ERK) in the colon. BTW inhibited the ERK/p-NF-κB signaling pathway and suppressed expression of cyclo-oxygenase-2 and inducible NO synthase in lipopolysaccharide-activated RAW 264.7 cells. BTW significantly promoted the synthesis of short-chain fatty acids in the gut, particularly acetate, propionate, isobutyric acid, and isovalerate. The results suggest that BTW can protect against DSS-induced UC. The mechanism may be partially attributed to regulating the balance of Th17/Treg cells and restoring the intestinal epithelial barrier.

Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway.

Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague–Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1β, and TNF-α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1β, and TNF-α; and lowered levels of colonic inflammation.