Ulcerative Colitis In Mouse Model Research Articles

Combined ROS Responsive Polydopamine-Coated Berberine Nanoparticles Effective Against Ulcerative Colitis in Mouse Model.

Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties. Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo. Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage. PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option.

Lactobacillus fermentum CKCC1858 and Lactobacillus plantarum CKCC1312 ameliorate the symptoms of ulcerative colitis in mouse model induced by dextran sulfate sodium

The objective of this study was to investigate the therapeutical action of Lactobacillus fermentum CKCC1858 and Lactobacillus plantarum CKCC1312 on ulcerative colitis (UC) and its mechanism. The results showed that L. fermentum CKCC1858 and L. plantarum CKCC1312 were able to relieve UC in DSS-induced mice, manifested in a noticeable increase in food intake, colon length, water intake and weight, and a marked decrease in histological scores and disease activity index. Further studies showed that L. fermentum CKCC1858 and L. plantarum CKCC1312 had the capacity to increase the level of mucin-2, zonula occludens-1 and interleukin-10, decrease the levels of interleukin-1β, interleukin-17A, interferon-γ, interleukin-6 and tumor necrosis factor-α, and regulated the genes correlated with immune. Simultaneously, we suggested that L. fermentum CKCC1858 and L. plantarum CKCC1312 possess the ability to alleviate UC via regulating the intestinal microbiome and genes expression, improving intestinal mucosa and promoting the synthesis of short-chain fatty acids.

Caffeic Acid Phenethyl Ester Attenuates Dextran Sulfate Sodium-Induced Ulcerative Colitis Through Modulation of NF-κB and Cell Adhesion Molecules.

Ulcerative colitis (UC) is a serious health condition and defined as inflammation in the colon. Untreated, UC can develop into colitis-associated cancer (CAC), for which effective medicines are not available. Natural products are a better choice to treat UC by alleviating the inflammation. Caffeic acid phenethyl ester (CAPE) is a phenolic compound and known for its beneficial effects, including antibacterial, anti-inflammatory, anti-diabetic, and anticancer. We aimed to study the effect of CAPE on dextran sulfate sodium (DSS)-induced UC in mouse model. Administration of CAPE to DSS-induced mice protected against colon damage by improving body weight of mice, reducing the weight of spleen, and increased colon length. In addition, administration of CAPE resulted reduced the activity of myeloperoxidase (MPO) and CD68+ positive cells. Furthermore, a significant decrease in the production of key cytokines and the expression of nuclear factor (p65-NF)-κB. Moreover, p65-NF-κB activation was reduced in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells from mouse origin. CAPE treatment leads to the reduced expressions of intercellular adhesion molecules (ICAM)-1 and vascular cell adhesion molecules (VCAM), both are key cell adhesion molecules. The results of this study clearly indicate that CAPE can potentially control inflammation in the colon and can be used as a therapy for UC.

M10, a Myricetin-3-O-b-D-Lactose Sodium Salt, Prevents Ulcerative Colitis Through Inhibiting Necroptosis in Mice.

BackgroundM10 is a derivative of Myricetin by adding a hydrophilic glycosylation group. Our previous study revealed that M10 by oral administration prevented colitis-associated colonic cancer (CAC) through attenuating endoplasmic reticulum stress in mice. In current study, we evaluated the inhibitory effects of M10 on ulcerative colitis in mice model, the mechanism of M10 in preventing colitis was further investigated.MethodsMice model of ulcerative colitis was induced by continuous oral dextran sodium sulfate (DSS). M10 was given gavage once a day for 12 consecutive weeks. Disease activity index (DAI) was recorded by analyzing the symptoms of colitis. Intestinal barrier was analyzed by the Immunofluorescence staining assay. The structure of microvilli of intestinal epithelial cells was analyzed under Transmission electron microscopy (TEM). TEM assay was also performed to determine the formation of necroptosis in the colonic epithelium with ulcerative colitis. We performed Western blotting assay to analyze the IL-6 and NF-κB pathways, as well as the cytokine cascades related to TNF-α signaling pathway during necroptosis.ResultsM10 by oral administration demonstrated a prevention of ulcerative colitis, showing a significant decrease of DAI as compared to the model mice. Pathological analysis indicated that M10 attenuated the degree of colonic inflammation in colonic tissues. M10 restored the structures of intestinal barrier damaged by DSS. M10 prevented the activation of the IL-6 and NF-κB signaling pathways in the inflamed colonic epithelium. Further, M10 prevented necroptosis in the inflamed colonic mucosal cells through down-regulating the TNF-α pathway. Importantly, M10 demonstrated higher activities in preventing ulcerative colitis than Myricetin and control drug Mesalazine.ConclusionsMyricetin derivative M10 prevents chronic ulcerative colitis through inhibiting necroptosis. M10 could be developed as a promising drug for the treatment of chronic ulcerative colitis.

Yarrow oil ameliorates ulcerative colitis in mice model via regulating the NF-κB and PPAR-γ pathways

Background/AimsUlcerative colitis (UC) is a chronic inflammatory disorder with indefinite etiology; however, environmental, genetic, immune factors and microbial agents could be implicated in its pathogenesis. UC treatment is lifelong, therefore; the potential side effects and cost of the therapy are significant. Yarrow is a promising medicinal plant with the ability to treat many disorders, owing to its bioactive compounds especially the essential oil. The main aim of this research was to investigate the therapeutic effect of the yarrow oil on colitis including the involved mechanism of action.MethodsIn 21-female C57BL/6 mice were divided into 3 groups; control group, colitis model group, and oil-treated group. Groups 2 and 3 received 5% dextran sulfate sodium (DSS) in drinking water for 9 days, and concomitantly, only group 3 was given 100 mg/kg yarrow oil. Mice were examined for their body weight, stool consistency and bleeding, and the disease activity indexes were calculated.ResultsOral administration of yarrow oil markedly repressed the severity of UC via the reduction of the inflammatory signs and restoring colon length. The oil was able to down-regulate nuclear factor kappa light chain enhancer of activated B cells (NF-κB), up-regulate peroxisome proliferator-activated receptor gamma (PPAR-γ), and enhance transforming growth factor-β expression. The oil normalized the tumor necrosis factor-α expression, restored the normal serum level of interleukin-10 (IL-10) and reduced the serum level of IL-6.ConclusionsYarrow oil mitigated UC symptoms and regulated the inflammatory cytokines secretion via regulation of NF-κB and PPAR-γ pathways in the mice model, however, this recommendation requires further investigations using clinical studies to confirm the use of the oil on humans.

Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice

Ethnopharmacological relevanceFuzi and ganjiang are widely used as traditional Chinese medicines (TCM) in China, Korea, Japan, and many other southeast Asian countries for treating ulcerative colitis (UC), emesis and heart failure for more than 1800 years. However, the underlying mechanism of fuzi, ganjiang and fuzi-ganjiang herb pair is still unclear. In our study, we explored the therapeutic effects of fuzi, ganjiang and fuzi-ganjiang herb pair against dextran sulfate sodium (DSS)-induced UC in mice model, along with the relevant mechanism. Materials and methodsThe contents of each marker compound in fuzi decoction (FD), ganjiang decoction (GD) and fuzi-ganjiang decoction (FGD) were determined using LC-MS/MS. During the experiment, bodyweight changes in each group were monitored every 5 days. On the day of sacrifice, colonic length, disease activity index (DAI) and spleen weight were also evaluated and histopathological examination was performed through hematoxylin & eosin (H&E) staining. The levels of myeloperoxidase (MPO) and inflammatory cytokines in colon tissues were determined by enzyme-linked immunosorbent assay (ELISA), and then the relative mRNA productions of inflammatory mediators, such as MPO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time polymerase chain reaction (PCR). Involvement of MAPK, STAT3 and NF-κB signaling pathways in the pathogenesis of UC was determined in each group using Western Blot (WB) analysis. ResultsCompared with fuzi and ganjiang single decoction, the content of the alkaloids derived from fuzi (especially the diester alkaloid with strong toxicity, hypaconitine) in fuzi-ganjiang herb pair decoction was reduced. Additionally, the 6-gingerol, which was not found in ganjiang single decoction, was retained in fuzi-ganjiang herb pair decoction. FD, GD, and FGD significantly restored the bodyweight reduction, colon shortening, DAI elevation, splenomegaly and histological score in DSS-induced UC mice. Furthermore, except for the failure of low dosage of ganjiang decoction (GD-L) on IL-17A, all FD, GD and FGD significantly inhibited the production of MPO and inflammatory cytokines, such as IFN-γ, TNF-α, IL-1β, IL-6, IL-10 and IL-17A, and suppressed the relative expression of inflammatory mediators, such as MPO, iNOS and COX-2 mRNA in colon tissues of DSS-induced mice. According to WB analysis, fuzi, ganjiang and fuzi-ganjiang combination inhibited the activation of MAPK, NF-κB and STAT3 signaling pathways. ConclusionsOur study demonstrated that fuzi, ganjiang and fuzi-ganjiang combination possess prominent anti-inflammatory activities against DSS-induced UC mice; the involved mechanism may be related to inhibition the activation of MAPK, NF-κB, and STAT3 signaling pathways.

A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice

BackgroundUlcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methodsSeparately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. ResultsOur results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of pro-inflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), pro-inflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. ConclusionIn the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

Anti-inflammatory and Anti-oxidant Effects of Licorice Flavonoids on Ulcerative Colitis in Mouse Model

ObjectiveLicorice (Glycyrrhizae Radix or Liquiritiae Radix) is traditionally used to treat various diseases including inflammation and gastric ulcers. Licorice is rich in flavonoid compounds and possesses anti-inflammatory activities. To investigate the protective effects of licorice flavonoids (LFs) in both acetic acid-induced and dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mouse model and its underlying mechanism. Acute UC was induced by intra-rectal acetic acid (4% v/v) after pretreatment with LFs (100, 200, and 400 mg/kg, p.o.), 0.9% saline (20 mL/kg, p.o.) or Sulfasalazine (SASP) (600 mg/kg, p.o.) for 10 d. Quantitative analysis of chemical components of LFs was also conducted by HPLC. Our results showed that pre-treatment with LFs significantly reduced the wet weight/length ratio of colon, percentage of affected area, macroscopic and histological damage scores in acid-induced UC mice. LFs also significantly decreased the oxidative stress and pro-inflammatory cytokines, upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and downregulated nuclear transcription factor kappa B (NF-κB) pathway. At last, LFs also showed obvious antiulcer effect on the DSS-induced UC model. The major components of LFs were licochalcone A, glabrone, licoflavone, and licoflavone B. This study demonstrates that the protective effect of LFs may at least in part be due to its anti-oxidant activity through Nrf2 pathway and anti-inflammatory activity through NF-κB pathway.