Colitis In Rats Research Articles

S1014 Cellular and Molecular Impact of the Melanocortin Receptor Agonist PL8177 in Dextran Sulfate Sodium-Induced Colitis in Rats

S1014 Cellular and Molecular Impact of the Melanocortin Receptor Agonist PL8177 in Dextran Sulfate Sodium-Induced Colitis in Rats

Potential protective effects of the water-soluble Chinese propolis on experimental ulcerative colitis.

To investigate the outcome of Chinese water-soluble propolis (WSP) on the inflammatory response and oxidative stress (OS) of colonic mucosa in rats with ulcerative colitis. Dextran sulfate sodium (DSS) was employed to establish the ucerative colitis (UC) rat model. Forty-eight male rats were arbitrarily separated into six groups, namely control, UC, low-dose water-soluble propolis (L-WSP), medium-dose water-soluble propolis (M-WSP), high-dose water-soluble propolis (H-WSP), and sulfasalazine (Sulfa). In this study, we adopted a method of pre-administration and reconstruction of the model that assessed the water-soluble propolis mediated protection against DSS-induced UC rats. Moreover, we examined the body weight (BW), disease activity index (DAI), bloody stool, colon length, and intestinal mucosal injury index of rats. In addition, using enzyme linked immunosorbent assays, we assessed indicators, such as, colonic myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-9 (IL-9), tumor necrosis factor-ɑ (TNF-ɑ), superoxide dismutase (SOD), malondialdehyde, and glutathione peroxidase (GSH-Px) levels. The pro-inflammatory cytokine expression, as well as OS, was increased in the model rats. However, upon WSP intervention, both pro-inflammatory cytokine levels and OS reduced dramatically, and the therapeutic effect was dose-dependent. WSP downregulates OS by enhancing the function of endogenous antioxidant enzymes like SOD and GSH-Px, that inhibit neutrophil activity, as well as diminish pro-inflammatory cytokines like TNF-ɑ, IL-6, and IL-9, along with mechanisms that attenuate intestinal inflammation in UC rat model.

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC.

Biochemical and histopathological evidence for beneficial effects of Empagliflozin pretreatment on acetic acid-induced colitis in rats

BackgroundUlcerative Colitis (UC) is a disorder which oxidative stress plays a critical role in its pathogenesis. Empagliflozin (EMPA) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been shown to have anti-inflammatory and antioxidative effects. The aim of this study was to investigate the protective effects of EMPA on acetic acid (AA) induced colitis in rats.MethodsA total of twenty-four rats were divided into four groups (six animals in each group) as follows: (1) Control group; (2) acetic acid (AA)-induced colitis group (AA); (3) EMPA treatment group (AA + EMPA); (4) Dexamethasone (Dexa) treatment group (AA + Dexa). Animals in pre-treatment groups received EMPA (10 mg/kg, i.p.) or dexamethasone (4 mg/kg, i.p. as reference drug) for four consecutive days before induction of colitis by intra-rectal acetic acid (4% v/v) administration. Twenty-four hours after AA administration, rats were sacrificed and the colon tissues were removed for histopathological and biochemical evaluations.ResultsPretreatment with EMPA significantly decreased colon weight/length ratio (81.00 ± 5.28 mg/cm vs. 108.80 ± 5.51 mg/cm) as well as, macroscopic (2.50 ± 0.57 vs. 3.75 ± 0.25) and histological scores (3.3 ± 0.14 vs. 1.98 ± 0.14) compared to the AA-induced colitis group (p < 0.01). Pretreatment with EMPA significantly reduced malondialdehyde (MDA) (324.0 ± 15.93 vs. 476.7 ± 32.26 nmol/mg p < 0.001) and increased glutathione level (117.5 ± 4.48 vs. 94.38 ± 3.950 µmol/mg, p < 0.01) in comparison to the AA-induced colitis group. Furthermore, a significant increase in catalase (44.60 ± 4.02 vs.14.59 ± 2.03 U/mg, P < 0.01), superoxide dismutase (283.9 ± 18.11 vs. 156.4 ± 7.92 U/mg, p < 0.001), and glutathione peroxidase (10.38 ± 1.45 vs. 2.508 ± 0.37, p < 0.01) activities were observed by EMPA pretreatment when compared to the AA-induced colitis group. These results were in line with those of the reference drug.ConclusionsIt is concluded that EMPA could effectively reduce the severity of tissue injury in experimental colitis. This protective effect may be related to the antioxidative effects of EMPA drug.

Bioadhesive Microcarriers Encapsulated with IL-27 High Expressive MSC Extracellular Vesicles for Inflammatory Bowel Disease Treatment.

Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSCIL-27 EVs) is developed to treat IBD. The MSCIL-27 EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSCIL-27 EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSCIL-27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSCIL-27 EVs-loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSCIL-27 EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.

Therapeutic potentials of mesenchymal stem cells in the treatment of inflammatory bowel disease in rats.

Interleukin-1beta (IL-1β) and interleukin-17A (IL-17A) have strong pro-inflammatory activities that are involved in inflammatory bowel diseases (IBDs). Mesenchymal stem cell (MSC) therapy is considered a promising treatment for IBD. This study was performed to understand the role of rat Nlrp3 inflammasome, Hmgb1, and pro-inflammatory cytokines (IL-1β and IL-17a) in the pathogenesis of IBD. Also, to evaluate the role of human umbilical cord blood-MSCs (hUCB-MSCs) in the management of IBD. The rats were in four groups: normal controls, indomethacin-induced IBD group, indomethacin-induced IBD rats that received phosphate-buffered saline (PBS), and the IBD group that received hUCB-MSCs as a treatment. The messenger RNA (mRNA) expression levels of rat Nlrp3, Hmgb1, IL-1β, and IL-17a were evaluated by quantitative real-time polymerase chain reaction.Histopathological examination of the small intestinal tissues of the studied rats was performed. There was a significant upregulation of the rat Nlrp3, IL-1β, IL-17a mRNA expression (p < 0.001 for the three parameters), and Hmgb1 (p < 0.05) in the untreated IBD group compared to the normal control group. In the MSC-treated group, IL-1β, IL-17a, and rat Nlrp3 mRNA expression significantly decreased compared to both the untreated IBD group and PBS group (p < 0.05 for all). hUCB-MSCs ameliorated IBD in rats by downregulating the pro-inflammatory cytokines (IL-1β and IL-17a) and other inflammatory mediators such as Hmgb1 and rat Nlrp3.

Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.

Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling.

Ulcerative colitis (UC) is an inflammatory bowel disease and associated with metabolic imbalance. Luteolin (LUT) reportedly exhibits anti-inflammatory activity. However, its regulatory effects on metabolites remain indistinct. Here, the effects of LUT on immune response and oxidative stress in UC were determined. Serum metabolomics profiles of UC rats treated with LUT were obtained utilizing liquid chromatography-mass spectrometry. The results revealed that LUT treatment alleviated colon tissue injury, colon shortening, weight loss, and inflammatory response in UC rats. Additionally, the levels of superoxide dismutase and total antioxidant capacity were elevated, but malondialdehyde content was reduced in serum of UC rats, while these changes were abrogated by LUT. Metabolomics analysis unveiled that l-malic acid, creatinine, l-glutamine, and l-lactic acid levels were remarkably decreased, while dimethyl sulfone, 5-methylcytosine, cysteine-S-sulfate, and jasmonic acid levels were notably increased after LUT treatment. Furthermore, differential metabolites primarily participated in d-glutamine and d-glutamate metabolism, glutathione metabolism, and citrate cycle pathways. In summary, these results demonstrated that LUT improved immune response, alleviated oxidative stress, and altered metabolites in UC rats. This study lays the root for further exploring the mechanism of LUT in the treatment of UC.

Protective effects of topiramate on acetic acid-induced colitis in rats through the inhibition of oxidative stress.

Ulcerative colitis is an intestinal inflammatory condition characterized by a rise in inflammatory mediator production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which is anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis was induced on the first day of the study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed, and colon tissues were removed for further macroscopic, histopathologic, and biochemical analyses. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as the improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and upregulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that the administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties, and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity.

Investigation of In vitro and In vivo Pursuits of Laurus nobilis Extract on Acetic Acid-induced Ulcerative Colitis in Wistar Rats

Investigation of In vitro and In vivo Pursuits of Laurus nobilis Extract on Acetic Acid-induced Ulcerative Colitis in Wistar Rats

Weissella confusa F213 ameliorated inflammation and maintained intestinal mucosa integrity in chemically induced colitis rats

ObjectiveThis study was performed to investigate the potential effects of Weissella confusa F213 (WCF213) on chemically-induced colitis rats. Twelve male Wistar rats were divided into three groups: T1 (saline sterile), T2 (2.5% dextran sulfate sodium (DSS)- for 7 days), and T3 (WCF213 for 14 days, continued with 2.5% DSS for 7 days). The disease activity index (DAI) was monitored. After sacrificing the rats, the colon was collected for length measurement, local TNF-α level, HE staining for histology, and ZO-1 expression by using immunohistochemistry.ResultsWCF213 administration prevented weight loss and haematochezia, maintained average colon length and alleviated the clinical symptom of colitis, such as diarrhoea, albeit statistically non-significant (p < 0.05) compared with the T2 group. The histopathology of WCF213-treated colitis rats showed better architecture and less inflammatory cell infiltration into colon tissue. WCF213 significantly maintained the expression of ZO-1 in the mucosa (p < 0.001) and markedly reduced mucosal TNF-α concentration (p < 0.001) compared with the DSS group. Hence, these findings suggested that WCF213 attenuated clinical symptoms and inflammation and maintained mucosal integrity in DSS-induced colitis in vivo.

Nanoencapsulation of Curcuma longa L. extract for the treatment of experimental colitis

Inflammatory bowel diseases (IBDs) are gastrointestinal chronic inflammatory diseases characterized by chronic and recurrent intestinal ulcerations. Curcuminoids are naturally occurring polyphenolic compounds with remarkable bioactivity; however, their low water affinity and bioavailability usually hinder their application. Encapsulation techniques can be coupled with extraction procedures to yield nanoparticles that may have enhanced properties. In this work, curcuminoids were extracted from rhizomes of Curcuma longa L. and simultaneously encapsulated using ultrasound. The characterization of the curcuminoids nanoparticles showed that particles ranging from 124 ± 81 to 252 ± 68 nm were formed, and the main properties of the curcuminoids were maintained after encapsulation. Experimental colitis was induced in rats by 2,4,6-trinitrobenzene sulfonic acid, and they were subsequently treated with 10, 25, or 50 mg kg-1 of nanoencapsulated curcuminoids for 7 days through gavage, during which the disease activity index (DAI) was evaluated. Then the rats were euthanized, and the distal colon was removed for macroscopic analysis and the assessment of the activity of the enzymes myeloperoxidase and N-acetylglucosaminidase. The dose of 25 mg kg-1 of nanoencapsulated curcuminoids reduced the DAI and the activity of inflammatory enzymes compared to the untreated group and was established as the minimum effective dose to be used in the treatment of this model of experimental colitis in rats.

Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress-Induced Th17-Polarizing Cytokines in Crohn's-like Colitis.

Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.

α-Terpineol Mitigates Dextran Sulfate Sodium-Induced Colitis in Rats by Attenuating Inflammation and Apoptosis.

Ulcerative colitis (UC) is one of the major inflammatory disorders of the gastrointestinal tract. α-Terpineol (αTL) is naturally present in several plants, and it belongs to the monoterpenes category. αTL possesses various pharmacological properties such as antioxidant, antibacterial, antifungal, anticancer, and antiulcer activities. Importantly, αTL has been reported to possess potent anti-inflammatory effects also. In this study, we hypothesize that αTL may have protective effects against dextran sodium sulfate (DSS)-induced colitis in Wistar rats. Animals were randomly allocated to 3 groups of 6 rats each. In group III, αTL was administered at a dose of 50 mg/kg b. wt. orally from days 1 to 14, while in groups II and III, 4% DSS in drinking water was given to rats ad libitum from the 7th to 14th days. After 24 h of the last dose of αTL, all animals were euthanized. αTL administration reduced the DSS-induced colonic disease activity index, tissue damage, and goblet cell disintegration. αTL suppressed the orchestration of mast cells in the inflamed colon, enhanced the immunostaining of NF-kB-p65, COX-2, iNOS, p53, caspase-9, and cleaved caspase-3, and suppressed the immunostaining of connexin-43, survivin, and Bcl-2. The activities of caspases-9 and -3 were reduced significantly by αTL pretreatment, as also confirmed by calorimetric assays. Moreover, αTL significantly attenuated the nitric oxide level and myeloperoxidase activity. Histological results further support the fact that αTL reduced DSS-induced colonic damage and reduced inflammatory cell infiltration. Overall, our findings suggest that αTL has strong protective effects against DSS-induced colitis by mitigating inflammatory and apoptotic responses.

Quinic acid ameliorates ulcerative colitis in rats, through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways.

In this study, the therapeutic effect of quinic acid (QA), which has anti-inflammatory activity, was investigated on acetic acid-induced colitis in male Wistar rats. Ulcerative colitis (UC) was induced in rats by acetic acid intrarectally, and the protective effects of QA in 10, 30, 60, and 100 mg/kg doses were investigated. Rats were treated for 5 days and their colon tissues were dissected out at the end. Macroscopic and histopathological examinations were performed in colon tissues. Also, the expression of inflammatory and apoptotic genes, including TLR4, IL-1β, INOS, IL-6, TNF-α, NF-κB, Caspase-3, Caspase-8, Bax, and Bcl-2, was measured. Biochemistry indices, such as malondialdehyde (MDA) and nitrite oxide (NO) content, in addition to, total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), and enzymes activities were also assessed. Colitis increased the levels of MDA and NO, and enhanced the inflammatory and apoptotic gene expressions, while reducing the SOD and CAT enzymes activity, and TAC levels in the colitis rats. Also, results showed that colitis was associated with the infiltration of inflammatory cells, epithelium damage, and edema in colon tissue. QA significantly ameliorated histopathological indices, oxidative stress, inflammation, and apoptosis in colitis rats. QA ameliorated UC through the inhibition of two TLR4-NF-κB and NF-κB-INOS-NO signaling pathways, which results in the reduction of colitis complications, including oxidative stress, inflammation, apoptosis and histopathological injuries in rats. Therefore it can be concluded, that QA exerts its therapeutic effects through antiapoptotic, antioxidant, and anti-inflammatory properties.

Voluntary Exercise-Mediated Protection in TNBS-Induced Rat Colitis: The Involvement of NETosis and Prdx Antioxidants.

Inflammatory bowel diseases (IBDs) are autoimmune disorders of the gut. It is increasingly clear that voluntary exercise (VE) may exert protection against IBDs, but the exact background mechanism needs to be elucidated. In the present study, we aimed to investigate the possible role of NETosis and the antioxidant peroxiredoxin (Prdx) enzyme family in VE-induced protection. Wistar Han rats were randomly divided into two groups: sedentary (SED) and VE. After the 6-week voluntary wheel running, animals were treated with 2,4,6-trinitrobenzene sulphonic acid (TNBS) as a model of colitis. Here, we found that VE significantly decreased inflammation and ulceration of the colon in the VE TNBS group compared with SED TNBS. We also found that VE significantly decreased the expression of protein arginine deiminase 4 (PAD4) and myeloperoxidase (MPO), and markedly reduced citrullinated histone H3 (citH3) compared with SED TNBS. Furthermore, VE caused a significant increase in the levels of Prdx6 in the control and TNBS groups. Taken together, we found that a prior 6-week VE effectively reduces inflammation in TNBS-induced colitis, and we suggest that the protective effect of VE may be mediated via the inhibition of NETosis and upregulation of Prdx6 antioxidant.

AMELIORATIVE EFFECT OF AVENA SATIVA (OAT) IN DINITROBENZENE SULPHONIC ACID INDUCED INFLAMMATORY BOWEL DISEASE IN RATS

Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal tract disease. There is an upsurge of IBD cases worldwide and there is no gold standard therapy and the drugs used to treat IBD are having many major side effects. Thus, there is a need for a better treatment option. This study aimed to evaluate the prophylactic role of Avena sativa (oat) in 2, 4-dinitro benzene sulphonic acid (DNBS) (120 mg kg-1) induced IBD in rats. Animals were randomly allocated to five groups- negative control, model control receiving only DNBS, group receiving A. sativa extract (500 mg kg-1 and 1 g kg-1 p.o.) and the last group receiving sulphasalazine (100 mg kg-1, p.o.). Colitis-induced rats treated with A. sativa and sulphasalazine restored their body weight, stool consistency, and bleeding in stool and significantly improved several biochemical parameters such as colonic glutathione content, lactate dehydrogenase, myeloperoxidase and lipid peroxides levels as compared to the model control group. Findings suggest that A. sativa possesses antioxidant and anti-inflammatory activity and can be useful in treating IBD.

Acupoint catgut embedding relieves colonic inflammatory injury by down-regulating NLRP3/Caspase-1 signaling pathway in rats with ulcerative colitis

To observe the effect of acupoint catgut embedding (CE) on Nod-like receptor protein 3 (NLRP3)/Caspase-1 signaling pathway in "deficiency-stasis" syndrome type ulcerative colitis (UC) rats, so as to explore its mechanisms underlying improvement of UC. A total of 58 male SD rats were randomly divided into control group (10 rats) and model group (48 rats). The "deficiency-stasis" type UC model was established by gavage of adenine and folium sennae solution for 4 weeks, followed by clycter of mixture solution of 5% trinitro-benzene-sulfonic acid and 50% ethanol. A total of 44 UC rats were randomized into model, salicylazosulfapyridine (SASP), non-acupoint CE, and acupoint CE groups (11 rats in each group). The catgut embedment was applied to bilateral "Zusanli"(ST36), "Shenshu"(BL23), "Pishu"(BL20), "Dachangshu"(BL25), "Geshu" (BL17) and "Tianshu"(ST25), or non-acupoints (the fat muscles of the buttocks), separately, once every two weeks, 3 times altogether. Rats of the SASP group received gavage of SASP solution, and those of the other groups received gavage of same amount of normal saline, once daily for 42 days. The rat's general conditions and the colon length were recorded, the disease activity index (DAI, 0 to 4 points) and colonic mucosal damage index (CMDI, 0 to 5 points) were calculated. Histopathological changes of the colonic mucosa tissue were observed after HE staining, and the tissue damage index (TDI, 0 to 6 points) was given. The levels of serum NLRP3, interleukin (IL)-1β and IL-18 were measured by ELISA, and the expression levels of NLRP3, Caspase-1, apoptosis-associated speck-like protein (ASC), IL-1β and IL-18 mRNAs were measured by fluorescence quantitative PCR. The expression levels of NLRP3 and Caspase-1 proteins in the colon tissues were measured by Western blot, and the immunoactivity of colonic ASC was detected by immunohistochemistry. Compared with the control group, the rats' body mass and colonic length were significantly decreased (P<0.01), and DAI score, CMDI score, TDI score, contents of serum NLRP3, IL-1β and IL-18, expression levels of colonic NLRP3, ASC, Caspase-1, IL-1β and IL-18 mRNAs, and NLRP3 and Caspase -1 proteins as well as colonic ASC immunoactivity were significantly up-regulated in the model group (P<0.01). Compared with the model group, both SASP and acupoint CE groups had a significant increase in body mass and colonic length (P<0.01), and a marked decrease in DAI score, CMDI score, TDI score, contents of serum NLRP3, IL-1β and IL-18, expression levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 mRNAs and NLRP3 and Caspase-1 proteins and ASC immunoactivity (P<0.01). The above indexes were improved in the acupoint CE group in relevant to those of the non-acupoint CE group (P<0.01). HE staining of colonic mucosal tissue showed obvious ulcerative surface, destroyed recess, disordered arrangement of glands, mucosal edema and congestion, infiltration of a large number of inflammatory cells in the model group, which was obviously milder in both SASP and acupoint CE groups. Acupoint embedding can alleviate colonic injury and inhibit inflammatory reaction in rats with "deficiency-stasis" type UC by down-regulating colonic NLRP3/Caspase-1 signaling.

Prevention of Inflammation Initiation on Acetic Acid-Induced Ulcerative Colitis in Rats by Malva nicaeensis All.

Aerial parts of Malva nicaeensis All. are preferred in the prevention and treatment of intestinal infections and hemorrhoids in Turkish traditional medicine. This study is planned to evaluate the pharmacological activity of M. nicaeensis extracts on rats with acetic acid-induced colitis. The plant material was subsequently extracted with n-hexane, ethanol, and water, respectively. All of these extracts were tested for efficacy in the acetic acid-induced rat colitis model. The aqueous and polysaccharide extracts regulated cytokine levels and antioxidant parameters. Furthermore, the aqueous extract in particular regulated myeloperoxidase and caspase-3 levels in this rat model. In addition, the polysaccharide-rich fraction was separated from the aqueous extract. The polysaccharide-rich fraction and aqueous extract regulated cytokine levels and antioxidant parameters. The aqueous extract also positively affected myeloperoxidase and caspase-3 levels. The phytochemical studies revealed that the aqueous extract had the highest phenolic content. In addition, the polysaccharide fraction was found to contain total sugars, sulfated groups, uronic acids, and total proteins in 78.4%, 0.9%, 1.5%, and 14.7%, respectively, and was rich in monosaccharide-type compounds, especially galactose (36.4%). M. nicaeensis was discovered to be a drug lead in the future treatment of irritable bowel diseases or as a complementary therapeutic agent that aided conventional treatments.

Evaluation of Ethanolic leaf extract of Cucumis melo var. agrestis in Acetic Acid-Induced Ulcerative Colitis on Rats

The crux of the present research work was to evaluate the therapeutic potential of Ethanolic leaf extract of Cucumis melo var. agrestis (ELECM)on Ulcerative Colitis in rats. The successful induction of Ulcerative Colitis was done by intra-rectal administration of 500 μl of acetic acid (4% v/v), rats were euthanized on day 8 by cervical dislocation under anesthesia. The pathological parameters such as colon weight, colon antioxidant enzymes (SOD, CAT), lipid peroxidase enzymes (MDA, MPO), inflammatory markers (TNF- α and IL-6), and histopathological aspects were estimated to evaluate the ELECM against the disease control. Sulfasalazine was used as positive control to compare the protective effect of the ELECM. The GC-MS analysis of ELECM confirms the presence of about 12 specific phytochemicals. Induction of ulcerative colitis was evidenced in the control group due to increased colon weight, lipid peroxidase enzymes, and immune markers also by alleviated levels of antioxidant enzymes in the rat colon. However, ELECM treated group almost reversed the effect of the disease control group, above all the histopathological response of the ELECM-treated group against the acetic acid-induced ulcerative colitis was almost the same as that of the control group, indicating the significant protective effect. Our present study suggests that ELECM extract has significant protective activity against acetic acid-induced ulcerative colitis, due to its higher antioxidant, moderate anti-inflammatory, and mild immune-suppressive effects, and the protective action might be due to the presence of active constituents such as flavonoids and total phenols as presented on the GC-MS analysis report.