Acetic Acid-induced Colitis Research Articles

Anti-inflammatory activity of Ziziphus jujuba hydroalcoholic extract in acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a common gastrointestinal (GI) disorder characterized by chronic inflammation. Current treatments primarily focus on symptom management, but they have inherent limitations. Global attention is increasingly directed towards exploring herbal remedies as complementary approaches. This study aims to investigate the effects of the hydroalcoholic extract of jujuba on an experimental model of ulcerative colitis. In this study, 15 male BALB/c mice were divided into three experimental groups. The first group served as the untreated UC model, acting as the positive control (PC). The second group received treatment with the hydroalcoholic extract of Ziziphus jujuba, while the third group was treated with mesalamine. UC was induced by injecting 100 μL of 4 % acetic acid (AA) intra-rectally several times. Treatment commenced after the onset of symptoms such as diarrhea and bloody stools. The mice were eventually euthanized ethically, and their spleen and intestinal tissues were collected for analysis. Evaluations included the Disease Activity Index (DAI), myeloperoxidase activity (MPO), nitric oxide (NO) levels, cytokine levels (IL-1β, IL-6, TNF-α), and gene expression (iNOS, COX-2, and cytokines). The hydroalcoholic extract of the jujuba plant significantly reduced MPO, NO, the DAI, and the production and expression of inflammatory cytokines, as well as the genes iNOS and COX-2, in the group receiving this extract compared to the positive control group (p<0.05). The study demonstrates that the hydroalcoholic extract of Ziziphus jujuba significantly reduces inflammation markers such as TNF-α, NO, MPO, IL-1β, and IL-6 in a mouse model of ulcerative colitis. Additionally, itdownregulates the expression of pro-inflammatory genes, including iNOS and COX-2. These findings suggest that Z.jujuba extract has potential as an effective anti-inflammatory treatment for managing ulcerative colitis symptoms.

Experimental colitis is comorbid with social interaction deficits and anxiety-like behaviors in mice: mechanistic intuitions into neuroinflammation and Claudin 5 expression in the hippocampus.

Inflammatory bowel disease (IBD) is accompanied by psychiatric disorders, including Schizophrenic-like manifestations. Although incompletely illustrated, intestinal mucosal membrane damage and blood-brain barrier (BBB) penetrability may have significant roles in psychiatric symptoms of IBD. This study aimed to investigate role of the Claudin-5 (CLDN5) (a regulator of the permeability of BBB) and neuroinflammatory response in the comorbid behavioral disorders in experimental colitis in mice. Acetic acid was used to induce colitis in mice. 7 days after induction of colitis, behaviors including social interaction and locomotor activity as well as anxiety-like behaviors were evaluated. Then, the colon was extracted for gross and microscopic evaluations. The expression of CLDN5, TNF-α, IL1β and IL23 was measured by RT-PCR in the colon and hippocampus. Histopathologic evaluations demonstrated mucosal, submucosal, and crypt-related damages in the colon. The negative and positive number of social interactions significantly increased in the colitis group. A considerable increase in locomotor activities (horizontal and vertical components) shown in the colitis group. Mice in colitis group spent less time in the central zone in the open field apparatus. Gene expressions of TNF-α, IL1β, and IL23 increased and CLDN5 decreased in the colitis group. The barrier function of the intestine and brain would be impaired, partially at least, following colitis (as we observed decrease in CLDN5 gene expression). Furthermore, we found that beside inflammatory response in the colon, a neuro-immune response triggered in the hippocampus following colitis. These alterations probably, mediated comorbid behavioral disorders in acetic acid-induced colitis in mice.

Evaluation of the immunomodulatory activity of probiotics mixture and sulfasalazine against acetic acid-induced colitis in a murine model.

Currently, the use of probiotics to treat inflammatory bowel diseases (IBD) is widely accepted because of their gut microbiota modulation capabilities and anti-inflammatory potential. The aim of this study is to examine the immunomodulatory outcomes of probiotics and sulfasalazine in the acetic acid-induced colitis murine model. The animals were randomly assigned to one of the seven groups. Following the induction of colitis, Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and sulfasalazine (SASP) were orally administered for 10 days. Subsequently, the in vitro anti-inflammatory effect on TNF-α and IL-10 in the supernatants of cultured spleen cells was assessed via ELISAs. Relative mRNA expression of ZO-1, MLCK, iNOS, TNFR2, ROR-γt, GATA-3, T-bet, and Foxp3 was determined using quantitative reverse‑transcription polymerase chain reaction (qRT‑PCR). The SASP plus probiotic mixture was more effective in alleviating colitis symptoms, and reducing disease activity scores, and mucosal inflammation. qRT-PCR analysis revealed a significant reduction in T-bet and RORγt levels, while Foxp3 and GATA-3 levels increased in the colons of colitis mice. In addition, the selected strains substantially inhibited the release of inflammatory markers. Administration of LA-5 + BB-12 + SASP resulted in considerably higher inhibition of NO production and cell proliferation than in the other groups (p < 0.001). Treatment with LA-5 + BB-12 + SASP also reduced TNF-α-mediated apoptosis in intestinal epithelial cells (IECs). Survey results highlight that the combination regimen could be a promising strategy for IBD therapy, warranting further study of its clinical application and long-term benefits.

Opuntia ficus-indica cladodes extract inhibits human neutrophil pro-inflammatory functions and protects rats from acetic acid-induced ulcerative colitis.

The increased production of reactive oxygen species (ROS) by human neutrophils can lead to oxidative imbalances and several diseases, such as inflammatory bowel disease (IBD). Opuntia ficus-indica (O. ficus-indica) is rich in bioactive substances with anti-inflammatory properties. This study aimed to identify the bioactive compounds present in aqueous cladodes extract (ACE) of O. ficus-indica using high-performance liquid chromatography (HPLC) and to test its effects on human neutrophil inflammatory functions and on ulcerative colitis (UC) induced by acetic acid (Aa) in rats. ROS production and degranulation by neutrophils were assessed by luminol-amplified chemiluminescence, enzymatic techniques, and western blotting. In vivo, the experiment involved seven groups of rats: a negative control group (NaCl), the acetic acid group (Aa), and groups treated with oral sulfasalazine (150mg/kg) or various doses of ACE for 7days. Colonic lesions were induced by an intra-rectal Aa injection, and inflammation was assessed. HPLC analysis identified gallic acid, catechin, caffeic acid, and ferulic acid as major compounds in ACE. In vitro, ACE inhibited neutrophil ROS production, including superoxide anion produced by NADPH oxidase, and significantly reduced myeloperoxidase activity and neutrophil degranulation. In vivo, ACE protected rats from Aa-induced histopathological damage of the colonic mucosa, significantly increased catalase, superoxide dismutase and reduced glutathione levels, and significantly suppressed the increases of plasma cytokines (TNF-α and IL-1β) observed in the Aa group. In conclusion, O. ficus-indica ACE has significant anti-inflammatory properties by restoring oxidative balance, indicating that it could be a potential source of therapeutic agents for inflammatory diseases, particularly UC.

The Effects of Mannyeon-hwan on Acetic Acid-induced Ulcerative Colitis in Rats

Objectives: This study was designed to verify the effects of Mannyeon-hwan (MNH) on acetic acid-induced ulcerative colitis in rats.Methods: Ulcerative colitis was induced in male Sprague-Dawley rats weighing approximately 250 g by injecting acetic acid through the anus. Rats were classified into four groups: normal group, control group (acetic-acid, AA), low concentration group (AA+MNH(L)), and high concentration group (AA+MNH(H)). Body weight, visual evaluation of the colonic mucosa, anatomical histological changes, and changes in the expression of proteins in colon tissue were compared and analyzed.Results: Compared to the control group, the MNH groups showed significant recovery from weight loss and mucosal damage. The expression of inflammatory proteins such as TNF-α, IL-6, IL-1β, NF-κB p65, MPO, and COX-2 were significantly decreased in the MNH groups compared to those in the AA group. In the MNH groups, significant changes in proteins involved in apoptosis such as caspase-3, BAX, and Bcl-2 were observed compared to those in the AA group. Additionally, changes in the expression of TNF-α, IL-6, IL-1β, NF-κB p65, BAX, and Bcl-2 were greater in the MNH(H) group than those in the MNH(L) group.Conclusion: Mannyeon-hwan was found to be effective in suppressing inflammation of the colonic mucosa in ulcerative colitis, inhibiting the expression of inflammation-related proteins, and suppressing damage to the colonic mucosa by regulating the expression of apoptosis-related proteins.

Umbelliprenin attenuates comorbid behavioral disorders in acetic acid-induced colitis in mice: mechanistic insights into hippocampal oxidative stress and neuroinflammation.

Inflammatory bowel disease (IBD) is often accompanied by psychiatric disorders. Emerging evidence suggests that neuroinflammation and oxidative stress contribute to the psychiatric symptoms associated with IBD. Umbelliprenin (UMB) possesses several pharmacological properties, including anti-inflammatory and antioxidant effects. This study aimed to investigate the protective effects of UMB on comorbid behavioral disorders in a mouse model of experimental colitis, focusing on its potential anti-neuroinflammatory and antioxidant activities. After inducing colitis with acetic acid, male NMRI mice were treated for 7 consecutive days with UMB, saline, or dexamethasone. Behavioral assessments included the forced swimming test (FST), splash test, open field test (OFT), and elevated plus maze (EPM). Histopathological changes in the colon were evaluated, and total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and the expression of inflammatory genes (TNFα, IL1β, and TLR4) were measured in the hippocampus. Colitis was associated with increased immobility time in the FST, reduced entries and time spent in the open arms of the EPM, decreased grooming behavior in the splash test, and reduced time spent in the central zone of the OFT. Colitis also resulted in a reduction in TAC and an increase in MDA levels and inflammatory gene expression in the hippocampus. UMB treatment mitigated the behavioral disorders associated with colitis, reduced neuroinflammation and oxidative stress in the hippocampus, and alleviated histopathological alterations in the colon. In conclusion, UMB may reduce behavioral disorders induced by colitis by decreasing oxidative stress and neuroinflammation in the hippocampus.

Combinatorial intervention with dental pulp stem cells and sulfasalazine in a rat model of ulcerative colitis

BackgroundUlcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo.MethodsUlcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue.ResultsThe investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression.ConclusionsCotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved.

Protective effect of freeze-dried extract of Persicaria bistorta Samp. on acetic acid-induced colitis model in rats: Involvement of nitric oxide and opioid system.

Inflammatory bowel disease is a chronic inflammatory disorder accompanied by occasional flare-ups, abdominal pain, and rectal bleeding.Persicaria bistorta Samp. is a medicinal plant repeatedly mentioned in traditional Persian medicine for the treatment of bleeding and tissue damage in different organs, including the intestines. The current study aimed to evaluate the effect of bistort root in an animal model of colitis. Freeze-dried aqueous extract of the plant (PB) was prepared and analyzed using liquid chromatography-mass spectrometry and high-performance liquid chromatography. The anti-inflammatory effect of oral PB (300, 500, and 700mg/kg) was evaluated in acetic acid-induced colitis in Wistar rats compared with negative control and positive control (dexamethasone). The role of nitric oxide (NO), opioid receptors, Toll-like receptors (TLR-4), interleukin (IL)-1β, IL-6, TNF-α, NF-κB, myeloperoxidase, and intestinal tissue damage using immunohistochemistry staining for cyclooxygenase-2 (COX-2) were also assessed. A total of 29 compounds were identified in the extract. The gallic acid content of the extractwas 4.973 ± 1.102mg/g. PB significantly ameliorated the gross morphological damage from 4.66 ± 0.577 in negative control to 1.33 ± 0.56 in PB 700 (p < 0.001). Also, PB 700 lowered the levels of TNF-α (p < 0.01), TLR-4 (p < 0.001), NF-κB (p < 0.0001), IL-1β (p < 0.0001), and IL-6 (p < 0.0001) compared to the negative control. Additionally, while blocking NO and opioid pathways, the therapeutic effect of the extract was not significant, compared to the negative control, suggesting that PB 700 has exerted its therapeutic effect via these two pathways. However, further mechanistic and clinical studies are recommended to confirm PB as a natural treatment for colitis.

Evaluation of Salvia officinalis in the Treatment of Acetic Acid-induced Ulcerative Colitis in a Rat Model

Abstract Introduction Ulcerative colitis (UC) is an inflammatory bowel disease that causes long-lasting inflammation and ulcers within the digestive tract. This study aims to determine the histochemical alteration of Salvia officinalis (sage), an anti-inflammatory and antioxidant herbal agent on UC. Materials and Methods The disease was induced in 37 Sprague-Dawley rats with 2 mL of 3% acetic-acid (AA) enema. The rats were divided into five groups: a control group (AA), two 5-aminosalicylic (5-ASA) groups treated either orally (AO) or rectally (AR) with a dose of 100 mg/kg, and two salvia groups treated with 300mg/kg salvia orally (SO) or rectally (SR). Histopathological analyses of the colon were done on day 7, and markers such as C-reactive protein (CRP), superoxide dismutase (SOD), and complete blood count were measured. Result In macroscopic evaluation, the AO group demonstrated the lowest involvement, followed by the SO, SR, AR, and AA groups, respectively (p = 0.01). There was no significant difference between the SO and AO groups (p = 0.10), and the SR and AR groups (p = 0.58). Regarding microscopic histopathological findings, the AO and SO group demonstrated the most satisfactory results, with no significant difference between the AO versus SO, and AR versus SR groups. Inflammation was resolved in all of the AO and SO subjects. Conclusion Salvia can be beneficial in the treatment course of UC by inhibiting inflammatory responses, increasing the growth and viability of intestinal mucosa, and its antioxidant effects. Therefore, we propose the prescription of salvia as an adds-on or alternative therapy in the management of UC.

Rutin mitigates acetic acid-induced ulcerative colitis: novel coloprotective mechanism.

Ulcerative colitis, an inflammatory bowel disease, is characterized by a status of oxidative stress and inflammation. Rutin is a natural flavonoid with many pharmacological activities and its role in acetic acid-induced ulcerative colitis through the high mobility group B1 (HMGB1)/ toll-like receptor-4 (TLR4)/ myeloid differentiation primary response protein 88 (MYD88)/ nuclear factor-kB (NF-kB) signaling pathway needs to be explored. Four experimental groups were divided into control group, rutin group: treated with 100mg/kg/day rutin orally for 10days, acetic acid (AA) group: given intracolonic instillation of AA to induce ulcerative colitis, and acetic acid with rutin treatment (AA/Rutin) group. Acetic acid caused a marked increase in the colon weight/length ratio and induced colonic histopathological changes, leading to a marked rise in the colonic histopathological scores. Acetic acid exhibited a significant rise in LDH and CRP serum levels as well as TOS colonic levels, accompanied by a marked decline in TAS colonic contents compared to the control group. Moreover, AA-induced activation of the HMGB1/TLR4/MYD88/NF-kB signaling pathway. Rutin demonstrated a significant decrease in the colon weight/length ratio, ameliorated the colonic histopathological changes induced by AA, and exhibited a marked decline in the colonic histopathological scores. Rutin showed a significant decrease in serum LDH, and CRP levels as well as colonic TOS contents when compared with the AA group. Rutin suppressed the colonic activation of the HMGB1/TLR4/MYD88/NF-kB signaling pathway. Rutin could be a promising coloprotective agent against AA-induced ulcerative colitis by targeting the HMGB1/TLR4/MYD88/NF-kB signaling pathway.

Persicaria lanigera (Polygonaceae) leaf extract exhibits antiulcerogenic and antiproliferative activities against acetic acid-induced ulcerative colitis and cotton pellet-induced granuloma tissue in rats

Objective: To assess the effect of leaf extract of Persicaria lanigera on cotton pellet-induced granuloma tissue formation and acetic acid-induced ulcerative colitis. Methods: Rats were randomly divided into six groups: normal control, negative control, positive control (dexamethasone or sulfasalazine) as well as Persicaria lanigera (100-600 mg/kg)-treated groups. The effects of the extracts on body weight, antioxidant, and hematological parameters, as well as mast cell proliferation, were assessed. In addition, a histological evaluation was conducted. Results: Persicaria lanigera extract significantly decreased the mean exudate amount and suppressed granuloma tissue formation in a concentration-dependent manner in rats (P&lt;0.05). Additionally, the extract significantly increased body weight, improved hematological profile, reduced the disease activity index score and malondialdehyde level, as well as enhanced catalase and superoxide dismutase activities (P&lt;0.05). Histological evaluation showed Persicaria lanigera extract alleviated acetic acid-induced colonic damages, as evidenced by decreased cell necrosis, edema, and inflammatory cell infiltration. Conclusions: Persicaria lanigera extract possesses antiproliferative, antioxidative, and anti-colitis activities. However, its underlying mechanisms of action need further investigation.

Neuroimmune response and oxidative stress in the prefrontal cortex mediate seizure susceptibility in experimental colitis in male mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have a vital role in the pathophysiology of IBD as well as seizure. IBD is associated with extraintestinal manifestations. This study aimed to explore the relationship between colitis and susceptibility to seizures, with a focus on the roles of neuroinflammation and oxidative stress in acetic acid-induced colitis in mice. Forty male Naval Medical Research Institute mice were divided into four groups: control, colitis, pentylenetetrazole (PTZ), and colitis + PTZ. Colitis was induced by intrarectal administration of acetic acid, and seizures were induced by intravenous injection of PTZ 7 days postcolitis induction. Following the measurement of latency to seizure, the mice were killed, and their colons and prefrontal cortex (PFC) were dissected. Gene expression of inflammatory markers including interleukin-1β, tumor necrosis factor-alpha, NOD-like receptor protein 3, and toll-like receptor 4, as well as total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels were measured in the colon and PFC. Histopathological evaluations were performed on the colon samples. Data were analyzed by t-test or one-way variance analysis. Colitis decreased latency to seizure, increased gene expression of inflammatory markers, and altered levels of MDA, nitrite, and TAC in both the colon and PFC. Simultaneous induction of colitis and seizure exacerbated the neuroimmune response and oxidative stress in the PFC and colon. Results concluded that neuroinflammation and oxidative stress in the PFC at least partially mediate the comorbid decrease in seizure latency in mice with colitis.

Therapeutic potential of Capparis spinosa in experimental model of acute acetic acid-induced colitis: Anti-inflammatory and antioxidant effects

IntroductionThis study examined the anti-inflammatory and antioxidant properties of Capparis spinosa L. (caper) in order to determine its medicinal potential in the treatment of acute colitis. MethodSixty male rats were divided into six groups. After the experimental period, distal colonic extension was collected for determination of colonic damage, oxidative stress markers, along with antioxidant markers. The impact of altered levels of inflammatory cytokines in colon tissues on the underlying mechanisms examined. ResultsThe results showed that administering different doses of caper led to significant decreases in TNF-α and IL-6 levels when compared to the control colitis group (p < 0.001). Caper treatment effectively lowered elevated oxidative stress factors (MDA, NO, and MPO) compared to the control colitis group (p < 0.001). Caper treatment resulted in a significant increase in antioxidant factors (CAT, SOD, and GSH) compared with the control colitis group (p < 0.001).Significant improvements in tissue repair were observed in caper-treated groups compared to positives and control colitis (p < 0.001). ConclusionThe study highlights caper may be useful in the treatment of acute colitis due to its ameliorative effects on inflammation, oxidative stress, and tissue repair.

Aspergillus awamori: potential antioxidant, anti-inflammatory, and anti-apoptotic activities in acetic acid-induced ulcerative colitis in rats

Ulcerative colitis (UC) is a chronic colonic inflammation with a significant health hazard. Aspergillus awamori (A. awamori) is a microorganism with various bioactive compounds with natural antioxidant and anti-inflammatory properties. The present work aimed to elucidate the protective and therapeutic effects of varying concentrations of A. awamori against acetic acid (AA)-induced ulcerative colitis (UC) in rats. Nine groups of albino male rats were established: a control negative group (G1), a control positive group (G2,AA), and preventive protocol groups (including G3A, G4A, and G5A) that received 100 mg, 50 mg, and 25 mg/kg b.w, respectively, of A. awamori orally and daily from the 1st day of the experiment and for 7 consecutive days. Then, they were subjected to one dose of AA intrarectally on day 8th. G3B, G4B, and G5B were termed as curative protocol groups that received one dose of AA on day 8th and then administered 100 mg, 50 mg, and 25 mg/kg b.w. of A. awamori, respectively, on day 9th and continued receiving these doses daily until day 16th. Rats in the AA group exhibited marked histopathological alterations of the distal colon, with an exaggeration of the DAI. In addition, a remarkable increase in oxidative stress was represented by the elevation of MDA and NO levels with a decline in SOD and GPx activities. In addition, upregulation of TNF-α, IL-6, and IL-1β mRNA expressions and downregulation of Muc2 and Nrf2 levels were detected. Unambiguously, a remarkable anti-inflammatory effect was noticed either in A. awamori prevented or treated groups expounded by reducing and regulating TNF-α, IL-6, and IL-1β with improved pathological lesion scoring. The Muc2, Nrf2, and bcl-2 gene levels were upregulated and restored also. In summary, the findings in this work reveal that A. awamori supplementation successfully alleviated the UC induced by AA, which had a better effect when administered before colitis induction.

Evaluation of the Protective and Healing Effects of Heracleum lasiopetalum Boiss on a Modified Acetic Acid-Induced Ulcerative Colitis Model in Rats

Background: Ulcerative colitis (UC), a chronic inflammatory condition of the colon with no definitive cure, necessitates the exploration of innovative therapies. Herbal remedies combined with conventional drugs may offer complementary benefits, enhancing treatment outcomes. Objectives: This study investigates the therapeutic effects of Heracleum lasiopetalum Boiss in a rat model of acetic acid-induced UC. Methods: Forty-eight adult female Wistar rats were randomly allocated to six groups (n = 8 per group) for each of two experiments. UC was induced by intracolonic administration of 1 ml of 4% acetic acid for 10 minutes. In the treatment groups, female rats received an oral gavage of 5%, 10%, and 40% aqueous plant extract, sulfasalazine (100 mg/kg), and distilled water for 6 days, starting 3 days after acetic acid administration. The protective groups received substances via oral gavage from 7 days before to 3 days after acetic acid administration. The extent of mucosal ulcers, hyperemia, inflammation, and mucosal bleeding was evaluated based on the Gerald Classification System Score (Macroscopic). Pathological assessment was conducted on prepared slides using the modified Wallace method (Microscopic). Changes in body and colon weight, along with food and water intake, were examined. Results: Significant changes in food intake were observed in both the extract and positive control treatment groups, exhibiting a notable difference compared to the negative control group (P &lt; 0.05). Body weight changes experienced a significant increase in the positive control treatment group compared to the negative control group (P &lt; 0.05), while no significant difference was evident between the extract and negative control treatment groups (P &gt; 0.05). In terms of water and food intake, as well as weight changes, no significant differences were detected among the various protective groups (P &gt; 0.05). Both microscopic and macroscopic examinations revealed a substantial enhancement in the colon of the extract and positive control treatment groups compared to the negative control group (P &lt; 0.05), with no significant difference observed between the protective groups (P &gt; 0.05). Conclusions: Heracleum lasiopetalum extract demonstrates a dose-dependent reduction in colon hyperemia, mucosal ulceration, inflammation, and fibrosis. This highlights its potential as a supplementary treatment option for UC, emphasizing the need for further investigation.

Effect of Tamarindus indica L. fruit pulp and seed extracts on experimental ulcerative colitis in rats.

Tamarindus indica L. which has anti-inflammatory, radical scavenging, and ulcer healing effects can be useful for the alleviation of inflammatory bowel disease (IBD). Therefore, the effects of T. indica fruit pulp (TIPE) and seed extracts (TISE) were investigated on experimental colitis. TIPE and TISE (125, 250, and 500 mg/kg) were made by maceration (ethanol/water: 80/30) and administered to male Wistar rats with acetic acid-induced colitis. Prednisolone (4 mg/kg) and mesalazine (100 mg/kg) were used as reference drugs. The colon tissues were examined for macroscopic and pathologic parameters and myeloperoxidase (MPO) and malondialdehyde (MDA) values. The total phenols were 45.7 ± 1.1 and 453.0 ± 3.3 mg/g in terms of gallic acid for TIPE and TISE, respectively. Both of the extracts significantly improved most of the investigated parameters including body weight loss, the weight of colons, indices of ulcers, and total colitis. MPO activity and MDA in the treatment groups (except for TIPE at 125 mg/Kg) significantly decreased compared to the control. Both TIPE and TISE were effective in the treatment of colitis however it seems that the effective ingredients were more concentrated in seeds rather than pulp extract so the highest dose of seed extract had a competitive effect with reference drugs. More studies are needed to introduce T. indica as a suitable complementary medicine or food for patients with IBD.

Mangiferin, A Naturally Occurring Glucosylxanthone, Induces Apoptosis in Caco-2 Cells In Vitro and Exerts Protective Effects on Acetic Acid-Induced Ulcerative Colitis in Mice through the Regulation of NLRP3.

Inflammatory bowel diseases (IBD), an inflammatory disease, include Crohn's disease and ulcerative colitis. Dysregulated autoimmune response to gut dysbiosis is mainly involved in the pathogenesis of IBD and is triggered by various inciting environmental factors. With its rising prevalence in every continent, IBD has evolved into a global disease, which is on the rise, affecting people of all ages. There is a growing incidence of IBD in the elderly population, as evidenced by epidemiological data. IBD is characterized by an inflammatory process that requires a lifelong treatment. The main challenge in IBD management is the adverse side effects associated with almost all of the currently available drugs. Hence, there is a search for drugs with more efficacy and fewer side effects. Natural products with great structural diversity and ease of modification chemically are being explored, as they were shown to control IBD by safely suppressing pro-inflammatory pathways. The present study aims at understanding the role of mangiferin, a COX-2 inhibitor isolated from tubers of Pueraria tuberosa in the treatment of IBD and colon cancer, in vitro on the Caco-2 human colon cancer cell line and in vivo in the acetic acid-induced IBD mouse model. In the acetic acid-induced colitis model, it prevented the decrease in length of the colon, mucosal erosion, and cellular infiltration in a dose-dependent manner. The expression levels of various pro-inflammatory markers like COX-2, IL1β, TNF-α, INF-γ, IL-6, NLRP3, and caspase-1 were downregulated in an acetic acid-induced mouse model on treatment with mangiferin in a dose dependent manner. Mangiferin also showed anticancer effects on Caco-2 cells by increasing the expression of Fas ligand, Fas receptor, FADD, caspase-8, and caspase-3 proteins, whereas Bid and Bcl-2 proteins showed decreased expression. These data suggest that mangiferin, an inhibitor of COX, induces apoptosis in colon cancer cells in vitro and protects mice from acetic acid-induced colitis in vivo.

Pomegranate seed oil alleviates colitis: Therapeutic effects achieved by modulation of oxidative stress and inflammation in a rat model

Pomegranate seed oil shows positive effects by limiting neutrophil activation and lipid peroxidation through its antioxidant and anti-inflammatory activities. This study evaluated the possible ameliorative effects of pomegranate seed oil, its actions on proinflammatory cytokines, and its antioxidant activity using an acute acetic acid-induced colitis model in rats. 32 male Sprague-Dawley rats were divided into 4 groups: control, colitis, 0.4 ml/kg, and 0.8 ml/kg pomegranate seed oil treatment after colitis. At the end of the experiment, histopathological and biochemical analyses of intestinal tissues and blood were performed. The study revealed that administering different doses of pomegranate seed oil dramatically reduced total oxidant levels, nuclear factor kappa B, proinflammatory cytokines, and myeloperoxidase activity and appreciably reduced colitis injury. These findings suggest that pomegranate seed oil may alleviate colitis symptoms effectively and exert protective effects through antioxidant, anti-inflammatory mechanisms.

Anti-inflammatory and protective effects of Pimpinella candolleana on ulcerative colitis in rats: a comprehensive study of quality, chemical composition, and molecular mechanisms.

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-α, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment.

Protective effects of Moringa oleifera against acetic acid-induced colitis in rat: Inflammatory mediators’ inhibition and preservation the colon morphohistology

Moringa oleifera decoction is used in folk medicine to alleviate various gastrointestinal ailments and has been shown in several studies to exhibit diverse biological activities: antioxidant, anti-inflammatory, and myorelaxant on intestine strips. However, its protective effect on pro-inflammatory cytokines in colitis remains to be ascertained. We investigated Moringa oleifera leaf aqueous extract activities on a rat model of acetic acid-induced colitis. Thirty-six rats were divided in random into six groups, and received either distilled water (10 mL/kg), the aqueous leaf extract of Moringa oleifera (25, 50, and 100 mg/kg) or the reference drug Loperamide (5 mg/kg) for 20 days. Animal body weight and food intake were followed-up. Colitis was induced on day 15, and daily stool weight was followed up. Animals were sacrificed (day 21), serum concentrations of pro-inflammatory cytokines MPO, IL-6, and TNF-α were evaluated, and the colon and liver preserved for histological examinations. After one-week pre-treatment, a significant (P < 0.05) weight increase was observed. At day 20, the extract significantly (P < 0.01) prevented weight loss. Food intake decreased by 36.33% in the colitis control, and by 4.34% in the extract (100 mg/kg) treated animals (P < 0.01). Moringa oleifera (100 mg/kg, day 20) decreased stool weights to 4.75±0.3 g (P < 0.05). The extract decreased (P < 0.01) MPO level. At 100 mg/kg, it significantly (P < 0.05) reduced IL-6 –0.58 ± 0.14 against 0.85 ± 0.00 ng/L in the colitis control. At the same dose, TNF-α levels decreased to 417.96 ± 0.17 ng/L (P < 0.001). Moringa oleifera alleviated colitis symptoms by reducing stool emission, alleviating inflammation, and preserving colon and liver cytoarchitecture.