Anti-ulcerative Colitis Research Articles

Protocatechuic Acid Alleviates Dextran-Sulfate-Sodium-Induced Ulcerative Colitis in Mice via the Regulation of Intestinal Flora and Ferroptosis.

Protocatechuic acid (PCA) is a natural component with multiple biological activities. However, the underlying mechanisms of the effects of PCA on anti-ulcerative colitis (UC) are unclear. A UC mouse model was established by allowing the mice to freely drink a dextran sulfate sodium solution. The mice were administered PCA intragastrically for 7 days. Histological pathology, intestinal flora, and ferroptosis regulators were determined in vivo. Additionally, ferroptotic Caco-2 cells were modeled to investigate the role of PCA in ferroptosis. Our results showed that PCA reduced the levels of the disease activity index, inflammatory factors, and histological damage in UC mice. We also found that the regulation of intestinal flora, especially Bacteroidetes, was one of the potential mechanisms underlying the protective effects of PCA anti-UC. Moreover, PCA downregulated the level of ferroptosis in the colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production compared with the model group. Similar effects of PCA on ferroptosis were observed in Erastin-treated Caco-2 cells. The results obtained using reactive oxygen species assays and the changes in mitochondrial structure observed via scanning electron microscopy also support these results. Our findings suggested that PCA protected against UC by regulating intestinal flora and ferroptosis.

Study on the Comprehensive Phytochemicals and the Anti-Ulcerative Colitis Effect of Saussurea pulchella.

Saussurea pulchella (SP) is a traditional medicinal plant that is widely used in folk medicine because of its diverse biological activities, particularly its anti-inflammatory effects. However, the alleviation effect of SP on ulcerative colitis (UC) has not yet been realized. To investigate the chemical composition and therapeutic effect of SP extract against UC. First, qualitative and quantitative analysis of SP 75% ethanol extract was performed by UPLC-Q/TOF-MS. Second, a dextran sodium sulfate (DSS) model of UC mice was developed to study the effects of SP on the symptoms, inflammatory factors, oxidative stress indexes and colon histopathology. Third, an integration of network pharmacology with metabolomics was performed to investigate the key metabolites, biological targets and metabolisms closely related to the effect of SP. From the SP ethanol extract, 149 compounds were identified qualitatively and 20 were determined quantitatively. The SP could dose-dependently decrease the DAI score, spleen coefficient and the levels of TNF-α, IL-6, iNOS, MPO and MDA; increase the colon length, GSH level and SOD activity; and protect the intestinal barrier in the UC mice. Moreover, 10 metabolite biomarkers,18 targets and 5 metabolisms were found to play crucial roles in the treatment of UC with SP. SP 75% ethanol extract could effectively alleviate the progression of UC and, therefore, could be classified as a novel natural treatment for UC.

Anti-ulcerative colitis effect of Calligonum comosum L'Hér. using rat model: Chemical, pharmacological and histopathological evidences

Calligonum comosum is a perennial shrub growing and widely used in traditional medicinal system in Saudi Arabia. The total phenolic content and in vitro antioxidant activity were compared between the water extract (WE) and methanol extract (ME). The protective potential against acetic acid (AA) induced ulcerative colitis (UC) was also evaluated in rats. The obtained results showed that the total phenolic content of the WE and ME were 8.378 ± 0.738 and 33.819 ± 0.488 µg/mL. The antioxidant properties of the two extracts were directly influenced by their total phenolic contents. The ME with higher phenolic contents and stronger antioxidant power was more effective than the WE in protection against AA-induced colitis. Phytochemical study of the ME led to the identification of three flavonoid derivatives: (-)-epi-catechin, quercetin-3-O-α-l-arabinofuranoside (Avicularin) and quercetin-3-O-β-d-glucuronide-6″-methyl ester by various spectroscopic methods. (-)-Epi-catechin was the major component while the other two compounds were obtained in minute quantities. The anti-ulcerative colitis effect of the ME can be explained by the presence of the antioxidant flavonoids since AA-induced colitis featured by imbalance between oxidant and antioxidant substances. Further support of such explanation was provided by HPLC quantification of (-)-epi-catechin in the ME and WE. The percentage in ME was higher than the WE but the difference was higher in term of Total Phenolic Content (TPC). These results support the traditional use of C. comosum as anti-ulcerative colitis.

Polysaccharide from Edible Alga Enteromorpha clathrata Improves Ulcerative Colitis in Association with Increased Abundance of Parabacteroides spp. in the Gut Microbiota of Dextran Sulfate Sodium-Fed Mice.

Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that Enteromorpha clathrata polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of Parabacteroides spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of Parabacteroides distasonis F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally, Parabacteroides distasonis F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria Parabacteroides distasonis.

Evidence for the Involvement of Cytokines Modulation and Prokinetic Properties in Gastric Ulcer Healing Effects of Helicteres sacarolha A. St.-Hil. A. Juss.

Preparations of Helicteres sacarolha (Malvaceae) leaves and roots are used in the form of decoction, infusion or maceration, to treat gastrointestinal disturbances, among others. Studies supporting some of its ethnomedicinal uses are still incipient. The present study aimed to investigate it potential effect on chronic ulcer, ulcerative colitis and possible prokinetic activities as part of its mechanism of action. The powdered leaves of Helicteres sacarolha (HEHs) was prepared by maceration in 70 % hydroethanolic solution. Its qualitative phytochemical constituents were investigated by direct flow injection analysis coupled to atmospheric pressure chemical ionization ion trap tandem mass spectrometry (FIA-APCI-IT-MSn ). The gastric ulcer healing effect was evaluated in acetic acid induced chronic ulcer in mice and the lesions were evaluated, including analysis of blood plasma cytokine levels. The prokinetic properties (gastric emptying and intestinal transit) were carried out in mice. Potential anti-ulcerative colitis activity was evaluated in rats using 2,4,6-trinitrobenzenesulfonic acid (5 % TNBS) -induced colitis. All animal experiments were carried out at the doses of 20, 50 and 250 mg/kg (p.o.). Eight compounds were putatively identified, specifically lariciresinol, and its derivatives, kaempferol derivatives and Tricin-O-Glc. The extract promoted increased gastric ulcer healing at all doses tested. Modulation of the cytokines involved inhibition of some key pro-inflammatory cytokines with maximum effect on IL-1β (70 %, 50 mg/kg, p<0.05), TNF-α (79 %, 20 mg/kg, p<0.01), and in the anti-inflammatory cytokines, namely IL-10 (57 %, 50 mg/kg, p<0.05) and IL-17 (79 %, only at 50 mg/kg, p<0.05). Histological findings demonstrated a mitigated inflammatory activity, and tissues undergoing regeneration. HEHs treatment caused delayed gastric emptying, and increased intestinal transit, but had no effect in the experimentally induced ulcerative colitis. We report for the first time putatively the presence of Lariciresinol and tricin derivatives from the hydroethanolic leaves extract of H. sacarolha. Its possible mechanism of actions of gastric ulcer healing involves cytokines modulation, mitigation of inflammatory response and tissue regeneration and provoked opposing effect in the gastrointestinal system. The present study demonstrates the therapeutic potential of H. sacarolha leaves used in Brazilian ethnomedicine in the treatment of chronic gastric ulcer.

Chemical Composition, Total Phenolic Content, and Anti-Ulcerative Colitis Effects of Extract and Essential Oil of Cupressus arizonica Greene Fruits

&#x0D; Ulcerative colitis (UC) is a chronic inflammatory bowel disease, which has a global prevalence. Also, the plants of the Cupressaceae family have prominent anti-inflammatory and wound healing effects, so they can be considered as promising candidates for the treatment of UC. In this study, the therapeutic effects of extract and essential oil of Cupressus arizonica Greene (C. arizonica) fruits in the animal model of UC were investigated. Total of 35 Wistar male rats were treated with essential oil and hydroalcoholic extract for one week after induction of colitis by acetic acid. The colonic segment cut for macroscopic and histological analysis. The total amount of extract phenol and flavonoid content was assayed by Folin–Ciocalteu and aluminum chloride colorimetric method, respectively. The essential oil was analyzed by gas chromatography/mass spectrometer (GC/MS). The extract at doses of 100 mg/kg and 250 mg/kg and essential oil at doses of 0.5 mg/kg showed significant effects on UC (P &lt; 0.05). The total phenolic content of hydroalcoholic extract in terms of mg of gallic acid/ g of extract was 191.625 ± 7.04 and the amount of total flavonoids in terms of mg of rutin/g of extract was 66.52 ± 6.51. Also, according to the results of GC/MS analysis, α-pinene was the major constituent of essential oil. Our results revealed that the extract and essential oil of C. arizonica fruits had therapeutic effects on UC, and this effect may be related to the presence of polyphenolic and terpene compounds.

Study on a novel enzymatic colon-targeted particle of total saponins of Pulsatilla by mechanical grinding technology in a solvent free system

Oral colon-targeting preparation can achieve targeted drug release in the lesion site and have a great application prospect. In this study, we presented the principle of particle design in the field of materials science into the preparation of colon-targeting preparation. Enzymatic Pulsatilla saponins Colon-targeting composite Microparticles (EPCM) were prepared by mechanical grinding without any organic solvent. Firstly, Response Surface Methodology (RSM) designed by Box-Behnken was used to optimize the preparation process of EPCM, and the structure of EPCM was characterized. All-Atomic and Molecular Dynamics (AAMD) was used to calculate the compatibility between drugs and coating materials before and after release, so as to explain the principle of colon- targeted drug release in this method. Then, colon-targeting characteristics of EPCM in vitro and in vivo were investigated by experiments. Finally, the pharmacodynamics effects of this composite microparticles on Ulcerative Colitis (UC) induced by DSS in C57BL/6 mice were evaluated. The results demonstrated that the colon-targeting composite microparticles could be prepared by mechanical grinding based on particle design principle. The composite microparticles have appropriate colon-targeting drug release performance in vitro and in vivo, and have good anti-ulcerative colitis effect. This study provides a new idea for the preparation of oral colon-targeting preparation of Traditional Chinese medicine, and has evident reference value for the study of coating isolation and powder modification of traditional Chinese medicine for other purposes.

Hemidesmus indicus var. Pubescens Root Ameliorates Dextran Sodium Sulfate-induced Ethanol Augmented Ulcerative Colitis in Rats

Abstract: Aim: Ulcerative colitis is a chronic, idiopathic, inflammatory condition of the colon. Studies have indicated that Hemidesmus indicus var. pubescens root extract possess antioxidant and antiulcerogenic activity. In this study, we aimed to evaluate the therapeutic effect of Hemidesmus indicus var. pubescens aqueous root extract in Dextran Sodium Sulfate induced, ethanol augmented ulcerative colitis in Wistar rats. Materials and Methods:The animals were administered with 2% Dextran Sodium Sulfate for 3 consecutive days orally followed by intracolonic instillation of 30% ethanol on 4th day. These animals were randomly divided into 4 groups viz.: Disease, Low dose extract -200 mg/kg, High dose extract -400 mg/kg and Sulfasalazine-500 mg/kg while healthy, untreated rats were assigned as the normal control group. Treatment with the extract and the standard was initiated on day 5, continued throughout the study period of 21 days. The effect of extract on Ulcerative Colitis was determined by evaluating haematological parameters, disease activity index, ulcer index, colon and spleen weight, biochemical parameters (malonaldehyde, glutathione, Catalase) and histopathological studies. Results: Animals treated orally with extract showed a reduction in Disease activity Index and Ulcer Index compared to disease control. Moreover, a significant decrease (p<0.01) in malonaldehyde and a significant increase (p<0.01) in catalase and glutathione levels compared to the disease group were also observed. Histopathological examination also showed augmentation of colonic architecture on treatment with extract, all of which confirmed the protective effect of extract against Dextran Sodium Sulfate- ethanol-induced Ulcerative Colitis. Conclusion: These results suggest that Hemidesmus indicusvar. pubescens root was able to attenuate Dextran Sodium Sulfate induced ethanol augmented ulcerative colitis indicating its anti-ulcerative colitis effects. Key words: Dextran Sodium Sulphate – Ethanol, Hemidesmus indicus var. pubescens,Indian sarasaparilla,Ulcerative colitis, Inflammatory Bowel Disease.

Schisandra chinensis (Turcz.) Baill. Protects against DSS-induced colitis in mice: Involvement of TLR4/NF-κB/NLRP3 inflammasome pathway and gut microbiota

Ethnopharmacological relevancethe fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese herbal medicine, which has been widely used in traditional Chinese medicine (TCM) for treating intestinal diseases. It is also traditionally used as health product and medicine in Russia and other countries. However, the effect of SC ethanol extract on anti-ulcerative colitis (UC) has not been systematically studied yet. Aim of the studyWe investigated the protective effects and underlying action mechanisms of SC extract (SCE) for UC treatment. Materials and methodsAn animal model of UC induced by dextran sulfate sodium (DSS) was established. After oral administration of SCE, the Disease Activity Index (DAI) was calculated, the length of colon measured, levels of proinflammatory factors determined, and histopathology carried out to assess the therapeutic efficacy of SCE on UC. The effects of SCE on the toll-like receptor 4/nuclear factor-kappa B/nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 inflammasome (TLR4/NF-κB/NLRP3 inflammasome) signaling pathway were evaluated by western blotting. High-throughput sequencing was done to reveal the effect of SCE on the change of the gut microbiota (GM) in mice with DSS-induced colitis. ResultsSCE significantly reduced the DAI score, restored colon-length shortening, and ameliorated colonic histopathologic injury in mice with DSS-induced colitis. SCE inhibited the inflammatory response by regulating the TLR4/NF-κB/NLRP3 inflammasome pathway in mice with UC. SCE also maintained gut barrier function by increasing the levels of zonula occludens (ZO)-1 and occludin. 16S rRNA sequencing showed that SCE could reverse the GM imbalance caused by UC. ConclusionsSCE can ameliorate DSS-induced colitis, and that its effects might be associated with suppression of the TLR4/NF-κB/NLRP3 inflammasome pathway and GM regulation, which may provide significant supports for the development of potential candidates for UC treatment.

Enhancement of antioxidant and anti-inflammatory activities of flavonoid primuletin in DSS induced colitis in C57BL/6 mice

Background: Inflammatory Bowel Disease is a syndrome comprising of Ulcerative colitis and Crohn’s disease characterized by rectal bleeding, abdominal pain, diarrhoea, progressive weight loss and rarely infections. There are lot of drugs like corticosteroids, immunosuppressants, antibiotics to treat the disease, yet no effective treatment for the disease is available apart from treating symptomatically. Flavonoids especially Primuletin was selected as test drug to prove its anti-ulcerative colitis activity and to establish it as an effective drug for treating IBD. Materials and methods: The in-vitro activity of Primuletin was investigated against RAW 246.7 cell lines in DMEM medium. The in-vitro cytotoxicity of the drug was estimated using MTT assay and the in-vitro estimation of inflammatory markers (TNFα, IL-6) was performed using indirect Elisa. Acute oral toxicity studies were performed to determine the toxicity of Primuletin in swiss albino mice. In-vivo anti-ulcerative colitis activity of Primuletin was investigated in DSS induced IBD in C57BL/6 and the results were compared with the standard drug. Results: Primuletin treatment significantly lowered the inflammatory markers in-vitro. In DSS Primuletin treatment significantly prevented drastic variations in the body weight of mice.

Exopolysaccharide from Lactobacillus rhamnosusZFM231 alleviates DSS‐induced colitis in mice by regulating gut microbiota

The exopolysaccharides (EPS) produced by Lactobacillus and other probiotics are associated with many benefits, such as immune regulation, antioxidant properties, antitumor effect, and regulation of intestinal microbe homeostasis. In the present study, the modulatory effect of EPS produced by Lactobacillus rhamnosus ZFM231 on the intestinal flora of mice with inflammatory bowel disease induced by dextran sulfate solution was investigated. Results indicated that weight loss, colonic length, the disease activity index score and colonic tissue damage in mice were significantly improved by EPS treatment. Compared with the model group, in the EPS-treated group, the diversity of and the composition of gut microbiota at both phylum and genus levels were found to recover to the levels of normal group, indicating the effective modulation on gut microbiota by EPS; short-chain fatty acids, including acetic acid, propionic acid and butyric acid produced by intestinal microbial metabolism, increased significantly; the level of anti-inflammatory factor transforning growth factor-β significantly increased and the level of pro-inflammatory factor tumor necrosis factor-α significantly decreased in the colonic cells of EPS-treated mice. It is clear that EPS produced by L. rhamnosus ZFM231 could find application in functional foods with the property of anti-ulcerative colitis. The experimental results provide new insights into the probiotic effect of EPS. © 2022 Society of Chemical Industry.

Ethnopharmacology, phytochemistry, and pharmacology of &lt;em&gt;Acacia saligna&lt;/em&gt; (Labill.) H.L. (Wendl.)

Acacia saligna Labill, also known as coojong, the blue-leafed wattle, golden wreath wattle, the orange wattle, the Western Australian golden wattle, and also known as Port Jackson willow in the place of Africa, is a little tree in the Fabaceae family. It is widely dispersed over Western Australia's south-west region, reaching the Murchison River in the north, and Israelite Bay in the east. It is indigenous to Australia. The most prevalent phenolic substances of this plant are benzoic acid, o-coumaric acid, caffeine, p-hydroxy benzoic acid and ellagic acid while the identified flavonoid compounds were naringenin, quercetin, and kaempferol. Due to its ability to develop into a woody shrub or tree in a variety of soil types, it is useful for many different things. In addition to being utilized as an ornamental plant, it has also been used for tanners, reforestation, animal feed, mine site rehabilitation, firewood, mulch, and agroforestry. The selected pharmacological activity of this plant includes antioxidant, antibacterial, antifungal, anti-ulcerative colitis, anticancer, cytotoxic and anti-hyperglycaemic etc.

Comparing healing effect against ulcerative colitis and toxicological effects of Rosmarinus officinalis: A comprehensive in vivo study of an edible plant in rats.

Ulcerative colitis (UC) is a chronic and inflammatory disorder of the gastrointestinal (GI) tract. UC usually worsens the daily life of the patient and may sometimes become mortal. There is no known remedy discovered against UC, yet. Rosmarinus officinalis consists of many flavonoids, phenolics, and terpenoids possessing various biological activities such as anti-inflammatory. For this reason, in the present study, anti-ulcerative colitis effect of ROME (Rosmarinus officinalis methanol extract) was investigated comprehensively by histopathological studies, a number of in vivo anti-inflammatory activities and several in vivo antioxidant activities, in addition to in vitro antioxidant activities and biochemical analyses. In addition, the toxic effects of ROME were examined. The results showed that ROME provided a significant healing effect against ulcerative colitis in rats. Both in vitro and in vivo assay results correlated with histopathological examinations. ROME exhibited minimal toxic alterations. When the results of rosemary are compared with the results of sulfasalazine, it can be suggested that instead of synthetic drugs with side effects, natural sources can be used for the treatment of various diseases. Although some activities of rosemary have been investigated in vitro in the previous studies, this is the first study revealing anti-ulcerative colitis effect of rosemary through histopathological studies, in vivo and in vitro assays as well as biochemical analyses overall. PRACTICAL APPLICATIONS: The results revealed and proved that ROME provided a significant healing effect against ulcerative colitis in rats. When the results of rosemary are compared with the results of sulfasalazine, a commercially available drug on the market, it can be suggested that instead of synthetic drugs with side effects, natural sources can be used for the treatment of various inflammatory diseases such as UC disease. In addition, ROME possesses limited toxic alterations, but not much more than the commercial drug. As a future perspective, lethal and therapeutic doses can be examined and determined. Thus, human studies can be started through this comprehensive in vivo study on rosemary which is commonly used as an edible plant and spice all over the world.

Pharmacological and metabolomic profiles of Musa acuminata wastes as a new potential source of anti-ulcerative colitis agents

Musa acuminata (MA) is a popular fruit peels in the world. Non-food parts of the plant have been investigated for their antioxidant and anti-ulcerative colitis activity. Metabolomic approaches were found to be informative as a screening tool. It discovered different metabolites depending on statistical analysis. The antioxidant activity content was measured by colorimetric method. Seventy six investigated metabolites were observed. The identities of some of these markers were confirmed based on their MS2 fragmentation and NMR spectroscopy. These include: cinnamic acid and its dimer 2-hydroxy-4-(4-methoxyphenyl)-1H-phenalen-1-one beside; gallic acid and flavonoids; quercetin, quercetin-3-O-β-d-glucoside, luteolin-7-O-β-d-glucopyranoside. GC/MS analysis of MA peels essential oil led to identification of 37 compounds. The leaves, pseudostem and fruit peels extracts were tested for their safety and their anti-ulcerative colitis efficacy in rats. Rats were classified into: normal, positive, prednisolone reference group, MA extracts pretreated groups (250–500 mg/kg) for 2 weeks followed by induction of ulcerative colitis by per-rectal infusion of 8% acetic acid. Macroscopic and microscopic examinations were done. Inflammatory markers (ANCA, CRP and Ilβ6) were measured in sera. The butanol extracts showed good antioxidant and anti-inflammatory activities as they ameliorated macroscopic and microscopic signs of ulcerative colitis and lowered the inflammatory markers compared to untreated group. MA wastes can be a potential source of bioactive metabolites for industrial use and future employment as promising anti-ulcerative colitis food supplements.

Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.

Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1β, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.

Oral colon-targeted mucoadhesive micelles with enzyme-responsive controlled release of curcumin for ulcerative colitis therapy

Although multitudinous nanoscale drug-delivery systems (DDSs) have been recommended to improve anti-ulcerative colitis (UC) outcomes, to enhance the mucoadhesion of nanosystems on the colon and specifically release the loaded drugs in response to the colon micro-environment would be critical factors. The application of curcumin (Cur), an acknowledged anti-UC phytochemical compound, for UC therapy requires more efficient nano-carriers to improve its therapeutic outcome. Herein, we developed the colon-targeted nano-micelles with mucoadhesive effect and Azo reductase-triggered drug release profiles for Cur delivery in UC treatment. Specifically, the amphiphilic block polymer containing the Azo-reductase sensitive linkage (PEG-Azo-PLGA), and catechol-modified TPGS (Cat-TPGS) were synthesized respectively. Based on the self-assembly of the mixed polymers, Cur-micelles (142.7 ± 1.7 nm of average size, 72.36% ± 1.54% of DEE) were obtained. Interestingly, the Cur-micelles exhibited the Azo-reductase sensitive particle dissociation and drug release, the enhanced cellular uptake and the prolonged retention on colonic mucosa, mediated by the strong mucoadhesion of catechol structure. Ultimately, Cur-micelles significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the intestinal flora and the levels of pro-inflammatory factors (MPO, IL-6, IL-1β, and TNF-α) related to TLR4/MyD88/NF-κB signaling pathway. This work provides an effective drug delivery strategy for anti-UC drugs by oral administration.

Protective Effect of Nelumbo nucifera Plant on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Rats

Objectives Ulcerative colitis is a global disease with increasing incidence and worldwide prevalence. So this study was undertaken to observe antiulcerative colitis activity of ethanolic extract of seeds of Nelumbo nucifera plant on dextran sodium sulfate (DSS)-induced ulcerative colitis in rats. Materials and Methods The effect of ethanolic extract of N. nucifera seed (EENNS) was studied on DSS-induced ulcerative colitis in albino Wistar rats for 11 days. Disease pathogenesis was assessed by evaluation of disease activity index (DAI) including the following parameters: change in body weight, stool constituency, rectal bleeding in animals. Estimation of myeloperoxide (MPO), nitric oxide (NO), and antioxidant parameters like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase level was performed in colon homogenate of animals. TNF-α (tumor necrosis factor- α) level was measured in colon homogenate using rat TNF-α ELISA kit. Statistical Analysis Significant differences (mean ± standard error of the mean) were detected using one-way analysis of variance followed by post-test using Graphpad prism 7.0 for multiple comparisons. Results EENNS (400 mg/kg) significantly improved the disease progression, body weight, and colon length of the animals as compared with the disease control group. Animal treated with EENNS (400 mg/kg) showed significantly improved colon mucosal damage index (1.66 ± 0.21) and DAI (11.66 ± 4.01) as compared with the disease control group. A higher level of SOD and catalase and a lower level of MDA were observed in animals treated with EENNS (400 mg/kg) as compared with the disease control group. Animals treated with EENNS (400 mg/kg) significantly decreased in NO and MPO levels as compared with the disease control group. A lower level of TNF-α (561.94 ± 14.84) was observed in EENNS (400 mg/kg)-treated animals as compared with the disease control group (736.92 ± 15.3). These observations were comparable to those of the standard control group. Histopathological data showed that EENNS (400 mg/kg) has shown reversal of tissue inflammation as compared with the disease group and evidence of less cell infiltration of lymphocytes and monocytes with normal structures of goblet cell and crypts as compared with the disease group. Conclusion EENS (400 mg/kg) can decrease the severity of the UC produced by DSS. EENNS showed a protective effect against DSS-induced ulcerative colitis which may be due to its antioxidant and anti-inflammatory activity.

The underlying mechanism of A-type procyanidins from peanut skin on DSS-induced ulcerative colitis mice by regulating gut microbiota and metabolism.

Ulcerative colitis (UC) is a kind of inflammatory bowel disease. Procyanidins have been found to prevent UC. However, most research has been focused on the alleviation effect of B-type procyanidins on UC and ignored those of A-type procyanidins. Hence, this study aims to investigate the anti-UC effect and the potential mechanism of A-type procyanidins by combining gut microbiome and metabolic profile. UC was induced by dextran sulfate sodium (DSS) in Balb/c mice, and then the mice were administrated with peanut skin procyanidins (PSP; rich in A-type procyanidins) for 9 days. Administration of PSP can ameliorate DSS-induced UC by mediating the intestinal barrier, the expression of inflammatory cytokines (TNF-α, IL-β, IL-6, and IL-10) and oxidative stress (MDA, T-SOD, NO, and iNOS) in mice. We observed that PSP affects the gut microbiota and colon metabolomic patterns of mice. The 16S rDNA sequencing showed increase in abundance of Lachnospiraceae_NK4A136_group, Oscillibacter and Roseburia and decrease of Bacteroides, Helicobacter, Parabacteroides, Escherichia-Shigella, and Enterobacter after PSP treatment. The colon tissue metabolome was significantly altered, as reflected by regulating taste transduction, mTOR signaling pathway, PI3K-Akt signaling pathway, and FoxO signaling pathway to improve the protection against UC. PRACTICAL APPLICATIONS: We investigated the anti-ulcerative colitis (UC) effect and its potential mechanism of peanut skin procyanidins (PSP). This suggests that PSP with abundant A-type procyanidins may be an effective candidate for dietary supplementation to alleviate the symptoms of UC by regulating gut microbiota and metabolism.

Anti-Ulcerative Colitis Activity of the Aqueous Leaves Extract of Khaya Senegalensis in Acetic Acid-Induced Colitis Rat Model

intestinal tract mainly colon. The disease is characterized by diarrhoea, blood in the stool, abdominal pain, and weight loss. Khaya senegalensis a plant commonly called dry zone Mahogany has been used as a remedy for several human gastrointestinal ailments. Objectives: To investigate the effect of aqueous leaves extract of Khaya senegalensis in the acetic acid-induced ulcerative colitis rat model. Study design: Preclinical randomised controlled trial. Methods: extraction was done using water, initial phytochemical screening and oral LD50 were determined. Colitis was induced in rats using 4% acetic acid administered intra rectally. The rats were divided into five groups, group 1 received water, groups 2, 3, and 4 received graded doses of leaves extract while group 5 received prednisolone as the positive control. Symptomatic parameters like the daily stool consistency and appearance and histological parameters such as ulcer area, lesson severity score, ulcer index, weight/length ratio and percentage cure were measured. Results; The leaves extract showed presence of alkaloids, tannins, flavonoids, saponins, steroids, volatile oil etc. The oral LD50 was greater than 5000mg/kg and the efficacy of the 400mg/kg extract administered group was not statistically significantly different from the positive control group that received the standard drug prednisolone. Conclusion: It can be concluded that the aqueous leaves extract of Khaya senegalensis possess significant anti-ulcerative colitis activity on acetic acid-induced ulcerative colitis rat models and appears to be safe.

Colonic Delivery of Celastrol-Loaded Layer-by-Layer Liposomes with Pectin/Trimethylated Chitosan Coating to Enhance Its Anti-Ulcerative Colitis Effects.

Herein, a flexible oral colon-targeting delivery system, mediated by electrostatic layer-by-layer alternate deposition with pectin-trimethyl chitosan (TMC) onto liposomes-loading celastrol (Cel/PT-LbL Lipo), was fabricated to enhance anti-UC efficacy. Along with layer-by-layer coating, Cel/Lipo exhibited surface charge reversal, a slight increase in particle size, and a sustained drug release profile in a simulative gastrointestinal tract medium. Based on its bilayer coating of polysaccharides, Cel/PT-LbL Lipo alleviated cytotoxicity of celastrol in colon epithelial NCM460 cells. Due to the strong mucoadhesion of TMC with mucin, PT-LbL Lipo benefited colon localization and prolonged retention ability of its payloads. Ultimately, Cel/PT-LbL Lipo significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the levels of pro-inflammatory factors related to the TLR4/MyD88/NF-κB signaling pathway. Collectively, this study demonstrates that the pectin/trimethylated chitosan coating may allow for Cel/PT-LbL Lipo to function as a more beneficial therapeutic strategy for UC treatment.