Sulfasalazine Group Research Articles

Colon-targeted self-assembled nanoparticles loaded with berberine double salt ameliorate ulcerative colitis by improving intestinal mucosal barrier and gut microbiota

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease marked by disturbances in intestinal mucosal barriers, persistent inflammation, oxidative stress, and dysbiosis of the intestinal microbiota. Traditional treatments often fail to adequately address these issues, primarily targeting inflammation. To address these limitations, this study developed an innovative approach using self-assembled nanoparticles for oral administration that target colonic inflammation. Berberine hydrochloride and ursodeoxycholic acid were combined to form a double salt (BeU), enhancing solubility and encapsulation. An amphiphilic polymer (FU-PA) was created by esterifying fucoidan with palmitic acid. FU-PA/BeU nanoparticles were prepared using the nanoprecipitation method and further encapsulated in acid-resistant sodium alginate microspheres (FU-PA/BeU NPs@MS) for targeted delivery to colonic lesions. The aggregation rate of nanoparticles with mucus was significantly reduced to 59 % of free berberine, while the apparent permeability coefficient increased by 2.4 times. In vitro, FU-PA/BeU NPs effectively targeted inflammatory macrophages, reducing IL-6 and NO levels while increasing IL-10 level (to 42.5 %, 26.8 %, and 539 % of the LPS-treated group, respectively). Additionally, the ABTS and DPPH radical scavenging capabilities of FU-PA/BeU NPs were 177.8 % and 151.7 % of BeU, respectively. In dextran sulphate sodium-induced UC mice, oral FU-PA/BeU NPs@MS significantly improved epithelial and mucosal barriers, restored gut microbiota diversity, reduced inflammation and oxidative stress. Remarkably, the mean colon length in the FU-PA/BeU NPs@MS group was 1.2 times longer than that in the sulfasalazine group. These dual-targeted FU-PA/BeU NPs@MS show great potential for UC treatment.

Protective effects and mechanisms of HuDiChangRong capsule on TNBS-induced ulcerative colitis in mice

Ethnopharmacological relevanceUC, characterized by chronic inflammation primarily affecting the colon and rectum, follows a protracted relapsing course marked by inflammation and an abundance of free radicals at the onset. Hudichangrong Capsule (HDCRC), a traditional Chinese medicinal formula, has long been employed in the treatment of UC and chronic bacillary dysentery, exhibiting positive therapeutic outcomes and a high rate of cure in clinical practice. Aim of the studyThe precise mechanism underlying its efficacy for UC remains elusive. Our objective was to investigate the anti-inflammatory effect and underlying mechanisms of HDCRC on TNBS-induced UC. Materials and methodsHere, we introduced HDCRC and induced UC using TNBS. SPF BALB/c mice were divided into 6 groups as follows: control group, colitis model group, colitis treated with sulfasalazine (400 mg/kg) group, and colitis treated with HDCRC (156, 312, and 624 mg/kg) groups. To assess the effects of HDCRC on colitis, we measured body weight loss, disease activity index (DAI), colon length, tissue damage, degree of inflammation, immune capacity, and oxidative stress. Additionally, we evaluated the TLR-4/MyD88 pathway and its downstream signaling using immunohistochemistry, real-time qPCR, and Western blot. Network pharmacology was used for main target prediction. 16s rRNA was employed for gut microbiota detechtion and UPLC-QTOF-MS was used for its and its metabonomics. ResultsHDCRC significantly slowed weight loss, ameliorated DAI, restored colon length, alleviated TNBS-induced tissue damage. It exerted the therapeutic effects via reducing oxidative stress, restoring immune balance, normalizing the inflammatory mediator levels and restoring intestinal barrier integrity. Furthermore, HDCRC mainly alleviate UC via suppressing the TLR-4/MyD88 pathway and its downstream signaling. The key components of the downstream pathway, including TLR-4, MyD88, NF-κB p65, ERK, p-JNK, p38, p-JAK1, JAK1, p-STAT3, and STAT3, were improved, thereby ameliorating the TNBS-induced injury. In addition, HDCRC could regulate gut microbiota (eg. Erysipelaloclostridium,etc.) and its metabonomics (eg. Vitamin B6 metabolism) in UC mice. ConclusionsIn conclusion, HDCRC exerts a protective effect against TNBS-induced UC in mice by inhibiting the TLR-4/MyD88 pathway and its downstream signaling, and partially JAK1/STAT3, suppressing oxidative stress, regulating immunity, restoring intestinal barrier integrity, and regulating gut microbiota and its metabonomics.

In vivo Investigation of the Therapeutic Potential of Ziziphus mauritiana Against Inflammatory Bowel Disease in Albino Wistar Rats

ABSTRACT Purpose: To examine the potential anti-inflammatory activity of the methanolic extract of Ziziphus mauritiana (MEZM) in inflammatory bowel disease conditions. Materials and Methods: A total of 36 adult male Albino Wistar rats were divided into six groups. The first group (normal control) was administered with normal saline, and the second group (disease control) was administered with 4% acetic acid via the rectal route. The third group (sulfasalazine group) received the standard treatment of 100 mg/kg sulfasalazine, while three test groups were administered with 100, 200, and 300 mg/kg of MEZM. On the 14th day, a macroscopic examination was conducted to assess colonic inflammation, ulceration, and levels of cytokines including interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin13 (IL-13), and tumour necrosis factorα (TNFα), which were estimated to investigate the inflammatory response. Result: The cytokine levels increased significantly in the disease control group compared to the normal control group with P value <0.0001. Treatment with sulfasalazine (100 mg/kg) and different doses of MEZM significantly reduced the levels of IL-4 and IL6 compared to the disease control group with P value <0.0001. Animals treated with MEZM (100 mg/kg) showed significant reduction in IL-13 and TNF-α levels with P value <0.001. Levels of IL-13 and TNF-α levels were significantly reduced in animals treated with sulfasalazine (100 mg/kg) and MEZM (200 and 300 mg/kg) with P value <0.0001. Conclusion: The study indicates that MEZM may exert potential anti-inflammatory action in IBD conditions.

Integrated strategy for mechanism of Shenling Baizhu San in treating ulcerative colitis based on colonic metabolomics and network pharmacology

Shenling Baizhu San(SLBZS) is a commonly used medicine for the treatment of ulcerative colitis(UC). This study aims to explore the mechanism of SLBZS in treating UC by using colonic metabolomics and network pharmacology. BALB/c mice were randomly divided into four groups: a blank group, a model group, an SLBZS group, and a sulfasalazine group. UPLC-Q-TOF-MS/MS technology was utilized to analyze the metabolic profiles of colonic tissue in mice, and differential metabolites and related metabolic pathways were screened. Based on the online database, active ingredients, action targets, and UC disease targets of SLBZS were screened. The protein-protein interaction(PPI) network of core targets of SLBZS in treating UC was constructed using STRING and Cytoscape 3.9.1. Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed using the DAVID database. A "metabolite-reaction-enzyme-gene" network was constructed to conduct a combined analysis of metabolomics and network pharmacology. SLBZS reversed the levels of 25 metabolites involved in various pathways such as D-glutamine and D-glutamate metabolism, caffeine metabolism, sphingolipid metabolism, arginine biosynthesis, lysine degradation, alanine, aspartate, and glutamate metabolism, glycerophospholipid metabolism, and pyrimidine metabolism in UC colonic tissue. 47 core targets of SLBZS in treating UC were involved in pathways including the MAPK signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, lipid and atherosclerosis, inflammatory bowel disease, and Th17 cell differentiation. Integrated analysis showed that glycerophospholipid metabolism and pyrimidine metabolism were key metabolic pathways in the treatment of UC with SLBZS. The results suggested that SLBZS improved colonic mucosal morphology by regulating colonic metabolites, down-regulated the expression of inflammation-related core target genes to reduce inflammation levels, and alleviated lipid metabolism disorders, thereby exerting a therapeutic effect on UC.

Moxibustion alleviates intestinal inflammation in ulcerative colitis rats by modulating long non-coding RNA LOC108352929 and inhibiting Phf11 expression

Long noncoding RNA (lncRNAs) are involved in the pathogenesis of ulcerative colitis (UC). Moxibustion, a traditional Chinese medicine, can improve symptoms in patients with UC and reduce intestinal inflammation in rats with UC. However, it remains unclear whether the ameliorative effect of moxibustion on intestinal mucosal inflammation in UC is related to lncRNAs. Thirty-two rats were randomly assigned to four groups: normal control, UC, moxibustion (MOX), and sulfasalazine (SASP). The UC rat model was induced by administering 4% dextran sulfate sodium (DSS) in drinking water. Rats in the moxibustion group underwent bilateral Tianshu (ST25) moxibustion using the herbs-partition moxibustion method. Rats in the sulfasalazine group received SASP solution via gavage twice daily for seven consecutive days. Our results revealed that, compared with the UC group [2.00 (1.00, 2.50)], the DAI score [0.25 (0.00, 0.50)] was significantly lower in the MOX group (P < 0.05). Compared with the UC group [13.00 (11.25, 14.00)], the histopathological score [5.50 (4.00, 7.75)] was significantly lower in the MOX group (P < 0.05). In addition, the CMDI and macroscopic scores were decreased in the MOX group (P < 0.05). Moxibustion significantly decreased the protein expression of inflammatory factors TNF-α, IFN-γ, and IL-1β in the colonic tissues of UC rats (P <0.05), thereby suppressing the inflammatory response. Moreover, moxibustion exerted a regulatory influence on colon lncRNA and mRNA expression profiles, upregulating LOC108352929 and downregulating Phf11 in rats with UC (P <0.05). Moxibustion also led to a reduction in the expression and colocalization of Phf11 and NF-κB in the colons of UC rats. Moreover, knockdown of LOC108352929 in rat enteric glial cells demonstrated a significant upregulation of TNF-α mRNA expression (P <0.05). In summary, these data illustrate that moxibustion effectively ameliorates DSS-induced colonic injury and inflammation while exerting regulatory control over the lncRNA-mRNA co-expression network in UC rats. Collectively, the in vivo and in vitro studies suggested that LOC108352929-Phf11 may serve as a potential biological marker for moxibustion in the treatment of UC.

Labetalol Ameliorates Experimental Colitis in Rat Possibly Through its Effect on Proinflammatory Mediators and Oxidative Stress.

Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1β, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1β, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.

Synthesis and evaluation of azo pro-drugs of flurbiprofen for colon targeting

This investigation for revealing the new synthsized azo prodrug of flurbiprofen which increase the potency of approach and decrease the associated adverse effects. Different class of amino acids which have synergestic effect with flurbiprofen for the treatment of UC and safely used in IBD, have been selected for synthesis of azo prodrug with fenoprofe. These azo prodrug of different classes has been further evaluated against physicochemical property, in vitro stability test and in vivo ulcer models in rats. The associated consequence reveals the successful synthesis of azo prodrug and also explored the significant therapeutic potential against TNBS induced UC model. Thin layer chromatography of all the intermediates and final compounds were performed on silica gel plates, using UV and iodine chamber for visualization of spots and single spots were obtained for the same,. Open capillary method was used to determine the melting points of the final products, which was found to be uncorrected. The objective of synthesizing such azo prodrugs of flurbiprofen which have improved aqueous solubility and lower log P values than that of flurbiprofen has been achieved. Such high values for aqueous solubility of these novel prodrugs confirm that they will reach intact into colon and will not get absorbed in the upper GIT. All physical and microscopical alteration has also been evaluated in standard (sulfasalazine) and all other azo prodrug groups, and significantly compared with colitis control. This evaluation confirmed that azo prodrugs significantly protect against TNBS induced colitis and show the similar results with sulfasalazine group. This finding proves the therapeutic potential of azo prodrug against ulcerative colitis as similar or better to sulfasalazine.

How Different Is The Status Of Depression And Anxiety In Patients With Rheumatoid Arthritis Receiving Methotrexate With Sulfasalazine Or Hydroxychloroquine?

Background — Depression and anxiety are among the most common clinical manifestations in patients with rheumatoid arthritis (RA). Sulfasalazine and hydroxychloroquine are important medications used to treat these patients. Objective — The goal of this study was to compare the occurrence of depression and anxiety in RA patients taking sulfasalazine or hydroxychloroquine for at least six months. Methods — This study included 300 patients with RA referred to inpatient or outpatient departments of a public hospital in northern Iran who were treated with two combination regimens of methotrexate and sulfasalazine or methotrexate and hydroxychloroquine. Participants were assessed on the standard Hospital Anxiety and Depression Scale (HADS) for symptoms of depression and anxiety. Results — The mean HADS depression subscale score was 6.77±3.98 in the hydroxychloroquine group and 3.50±3.53 in the sulfasalazine group (p&lt;0.001). The mean HADS anxiety subscale score was 7.66±4.43 in the hydroxychloroquine group and 5.34±4.35 in the sulfasalazine group (p&lt;0.001). Multiple linear regression analysis revealed a significant difference in the incidence of depression and anxiety between the two treatment groups. Conclusion — A higher prevalence of depression and anxiety was observed in RA patients treated with methotrexate and hydroxychloroquine versus those treated with methotrexate with sulfasalazine.

Moxifloxacin's Therapeutic Effects in AA-Induced Colitis: Anti-Inflammatory Action through NF-κB Pathway Inhibition, Including TNF-α Pathway and Downstream Inflammatory Processes

Objectives: The aim of the present study was to evaluate possible therapeutic effects of moxifloxacin against acetic acid-induced colitis in a rat model.&#x0D; Methods: Forty adult Wistar rats were separated into 4 groups, including the negative control group, acetic acid (AA) group, AA + sulfasalazine (100 mg/kg/day) group, and AA+ moxifloxacin (MFX) (8 mg/kg/day) group. Experimental colitis was induced in rats by rectal administration of (4%v/v) acetic acid. Rats with colitis were received either MFX 8mg/kg/day or sulfasalazine 100mg/kg orally for 7days.The parameters measured are macroscopical assessment, colon weight (indicator of edema) and the measurement of concentrations of the proinflammatory cytokine TNF-α, oxidative stress marker malondialdehyde (MDA), adhesion molecule selectin and the inflammatory mediator NF-κB in colonic tissue homogenate.&#x0D; Results: This study had shown that AA elevate macroscopical scores, colon weight and biochemical homogenate parameters and all measured parameters were significantly reduced by both moxifloxacin and sulfasalazine with nonsignificant difference between them.&#x0D; Conclusions: The study explain that moxifloxacin possesses therapeutic potential in in AA induced colitis and its anti-inflammatory actions may involve inhibition of NF-κB inflammatory pathways including TNF-α pathway with its downstream inflammatory process such as elevation of adhesion molecule synthesis and oxidative species overproduction in the colonic tissues.

Comparative treatment of Sulfasalazine+Ezetimibe combination and Sulfasalazine in a rat model with induced colitis.

Ulcerative colitis is a chronic inflammatory disease with high mortality and morbidity worldwide. It causes inflammation in the lining of the colon, resulting in several symptoms that negatively impact the quality of life. Unfortunately, there is currently no known cure for this condition. Therefore, it is crucial to explore alternative treatment approaches. This research aimed to investigate the anti-inflammatory and antioxidative effects of a combination therapy involving Sulfasalazine+Ezetimibe compared to Sulfasalazine alone in a rat model of ulcerative colitis. Forty adult rats were divided into four groups for this study. The groups consisted of a control group (negative control), an acetic acid group (positive control), an acetic acid+Sulfasalazine (100 mg/kg per day) group, and an acetic acid+Sulfasalazine (50 mg/kg)+Ezetimibe (5 mg/kg) group. Rats were treated for one week, and colitis was induced by administering 2 ml of 4% (v/v) acetic acid inter-rectally. After sacrifice, the colonic tissue homogenate was analyzed for several markers, including proinflammatory cytokines (TNF-α, IL-1β, NF-κB), oxidative stress markers (malondialdehyde, myeloperoxidase), and adhesive molecule markers (E-selectin, ICAM-1). Sulfasalazine and the combination of Sulfasalazine+Ezetimibe significantly reduced the colonic levels of TNF-α, IL-1β, NF-κB, MDA, and E-selectin in the homogenate. However, the combination therapy of Sulfasalazine and Ezetimibe demonstrated a superior effect.

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice

Context Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. Objective This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. Materials and methods Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. Results Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1β and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1β, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. Discussion and conclusion Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1β, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

Inhibition of xCT by sulfasalazine alleviates the depression-like behavior of adult male mice subjected to maternal separation stress

Maternal separation (MS) can induce emotional disorders. Our previous study reported that MS resulted in depression-like behavior. In this study, we aimed to explore the role of xCT in depression-like behavior in adult mice subjected to MS stress. Pups were divided into the control group, the control + sulfasalazine (SSZ, 75 mg/kg/day, i.p.) group, the MS group, and the MS+SSZ group. After MS, all pups were raised until PD60. Then, the depression-like behavior was detected by the novelty suppressed feeding (NSF) test, the forced swimming test (FST), and the tail suspension test (TST). The synaptic plasticity was examined by electrophysiological recordings and molecular biotechnology. The data showed that, compared with the control group, the mice in the MS group presented depression-like behavior, impairment of long-term potentiation (LTP), a reduction in the number of astrocytes, and activation of the microglia. Moreover, the expression of xCT was increased in the prefrontal cortex of MS mice, the EAAT2 and the Group Ⅱ metabotropic glutamate receptors (mGluR2/3) were decreased, and the level of pro-inflammatory factors was increased in the prefrontal cortex. After the administration with SSZ, the depression-like behavior and the impairment of LTP were alleviated, the number of astrocytes was increased, and the microglial activation was inhibited. Moreover, the levels of EAAT2 and mGluR2/3 were ameliorated, the over-activation of the microglia was mitigated, and the levels of glutamate and pro-inflammatory factors were decreased. In conclusion, the inhibition of xCT by SSZ could alleviate depression-like behavior partly via modulating the homeostasis of the glutamate system and dampening neuroinflammation.

Sulfasalazine inhibits esophageal cancer cell proliferation by mediating ferroptosis.

This study aimed to explore the potential mechanism by which sulfasalazine (SAS) inhibits esophageal cancer cell proliferation. A cell counting kit-8 (CCK-8) assay was used to detect the effect of SAS (0, 1, 2, and 4 mM) on the proliferation of TE-1 cells. Subsequently, TE-1 cells were divided into control group, SAS group, SAS + ferrostatin-1 (ferroptosis inhibitor) group, and SAS + Z-VAD (OH)-FMK (apoptosis inhibitor) group, and cell proliferation was measured using a CCK-8 assay. Real-time quantitative polymerase chain reaction and western blotting were used to determine the expression of solute carrier family member 7 11 (SLC7A11, also called xCT), glutathione peroxidase 4 (GPX4), and acyl-CoA synthase long-chain family member 4 (ACSL4) in TE-1 cells. Measurement of ferroptosis in TE-1 cells was achieved by flow cytometry. Compared with the control group (0 mM SAS), the proliferation of TE-1 cells was significantly inhibited by different concentrations of SAS for different time lengths, and 4 mM SAS treatment for 48 h could obtain the maximum inhibition rate (53.9%). In addition, SAS treatment caused a significant decrease in the mRNA and protein expression of xCT and GPX4, and a significant increase in ACSL4 expression in TE-1 cells treated with SAS. Flow cytometry results showed that the ferroptosis level was significantly increased after SAS treatment. However, the activation of ferroptosis by SAS was partially eliminated by treatment with ferrostatin-1 or Z-VAD (OH)-FMK. In conclusion, SAS inhibits the proliferation of esophageal carcinoma cells by activating the ferroptosis pathway.

Mechanism of tryptanthrin in treatment of ulcerative colitis in mice based on serum metabolomics

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P&lt;0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

Ibudilast ameliorates experimentally induced colitis in rats via down-regulation of proinflammatory cytokines and myeloperoxidase enzyme activity

Objectives: This study was carried out to explore the possible anti-inflammatory effect of ibudilast on acetic acid-induced colitis in rats. Methods: Fifty adult Wistar rats were separated into 5 groups, including the control group, acetic acid group, acetic acid + vehicle, acetic acid + sulfasalazine (100 mg/kg/day)group, and acetic acid + ibudilast (30 mg/kg/day) group. Colitis was induced in rats by the inter-rectal installation of 2 ml of 4% (v/v) acetic acid. Sulfasalazine and ibudilast were administered orally for ten days after 2 hours of induction. Results: The treatment with ibudilast significantly reduced disease activity index (DAI), macroscopic colonic scores (MAC), and histopathological changes induced by acetic acid. Also, ibudilast markedly decreased the expression of proinflammatory markers (TNF-α and IL-1β) in colonic tissue. Moreover, ibudilast inhibited myeloperoxidase (MPO) enzyme activity that was increased by acetic acid. Conclusion: Therefore, ibudilast may have a therapeutic effect in the management of ulcerative colitis.

Sulfasalazine prevents lung injury due to intra-abdominal sepsis in rats: possible role of Nrf2 and angiopoietin-2

This study aimed to investigate the effect of sulfasalazine in preventing and treating intra-abdominal sepsis-induced acute respiratory distress syndrome (ARDS) in a rat model. Forty male Wistar albino rats were used. The rats were randomly divided into four equal groups, and sepsis was induced in 30 rats by intraperitoneal administration of a fecal saline solution prepared from rat feces. Group 1: normal control (n=10) [non-surgical], Group 2: fecal intraperitoneal injection (FIP) (n=10) [untreated septic group], Group 3: FIP+saline (placebo) (n=10) [saline administered intraperitoneally], Group 4 (n=10): FIP+sulfasalazine [250 mg/kg per day administered intraperitoneally]. Computed tomography was performed and blood samples were collected for biochemical and blood gas analysis. The lungs were removed for histopathological studies. Statistically significant reductions in interleukin (IL)-6, IL1-β, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and angiopoietin-2 (ANG-2) levels were observed in the sulfasalazine group compared to the FIP+saline group (P<0.001). Nrf2 levels were significantly higher in the sulfasalazine-treated group than in the FIP and FIP+saline groups (P<0.01). Lung tissue scores were significantly reduced in the sulfasalazine group compared to the other sepsis groups. The Hounsfield unit (HU) value was significantly lower in the sulfasalazine group than in the FIP+saline group (P<0.001). PaO2 values were significantly higher in the sulfasalazine-treated group than in the FIP+saline-treated group (P<0.05). Sulfasalazine was shown to be effective in preventing and treating ARDS.

Phytochemical Screening and Antioxidant Activity of Uncaria tomentosa Extract

Background: Uncaria tomentosa is a traditional medicinal herb with antiviral, antioxidant, immunostimulating, anti-inflammatory, and anticancer effects. Objective: The present study was conducted to evaluate the antioxidant capacity in vitro and in vivo and the phytochemical analysis of Uncaria tomentosa. Materials and Methods: The plant extract was screened for phytochemical compounds and antioxidant capacity in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and in vivo using acetic acid-induced colitis. Colitis was induced in rats by transrectal administration (5 mL/kg) of 4% (v/v) acetic acid. Forty adult albino rats were divided into four groups: control group, acetic acid group, acetic acid + sulfasalazine (100 mg/kg/day) group, and acetic acid + Uncaria tomentosa extract (250 mg/kg/day) group. After inducing colitis, sulfasalazine and Uncaria tomentosa extract were given orally for 10 days. Data were statistically analyzed, and P &lt; 0.05 was considered statistically significant throughout the study. Results: Preliminary phytochemical study showed that Uncaria tomentosa extract contains flavonoids, phenols alkaloids, saponin, and terpenoids. In the DPPH assay, the extract exhibited considerable antioxidant capacity in a dose-dependent manner. Also, Uncaria tomentosa extract dramatically decreased oxidative stress parameters, such as myeloperoxidase enzyme activity and malondialdehyde in colonic tissue. Moreover, Uncaria tomentosa treatment attenuated macroscopic colonic scores and histopathological changes induced by acetic acid. Conclusion: The findings of this study show that Uncaria tomentosa extract could be a source of natural antioxidants and may have a therapeutic effect on ulcerative colitis.

Exercise Improves Clinical Symptoms, Pathological Changes and Oxidative/Antioxidative Balance in Animal Model of Colitis.

Ulcerative colitis is one of the major phenotypic forms of inflammatory bowel diseases. The present study aimed to investigate the effect of force swimming exercise on clinical symptoms (disease activity index; DAI), colon histopathology, inflammation and fibrosis, and oxidant/antioxidant balance in dextran sulfate sodium (DSS)-induced colitis mice. Male C57BL6 mice were randomly divided into five groups (n = 6 each): control, exercise, colitis, colitis + sulfasalazine, and colitis + exercise. Exercise was performed by forced swimming six weeks before and during the experiment. Colitis was induced by 1.5% DSS in drinking water. The animals were evaluated for body weight changes and DAI (including changes of body weight, stool consistency, rectal bleeding, and prolapse) during the induction of colitis and treatment. At the end of experiment, colons and spleens were evaluated by H and E and Masson Trichrome stainings. Oxidant (Malon dialdehyde; MDA), and antioxidant markers [total thiol groups, superoxide dismutase (SOD), and catalase activity] were also measured in colon tissue. Results indicated that exercise in colitis mice significantly improved DAI, colon length, spleen weight, and histological injury score and alleviated fibrotic changes in colon tissue that were comparable to sulfasalazine group. Exercise also restored the oxidant/antioxidant balance in colitis mice by reducing MDA and increasing antioxidative markers including total thiol groups, SOD, and catalase activity. Taken together, aerobic exercise could improve clinical symptoms and colonic inflammation through, at least, the balancing the oxidative stress markers. Thus, it can be considered in management of colitis patients as effective method.

Effects of sulfasalazine in axial spondyloarthritis on COVID-19 outcomes: real-life data from a single center

Introduction Compared to biological agents, little is known about the impact of sulfasalazine therapy on COVID-19 outcomes in patients with Axial Spondyloarthritis (AxSpA). Therefore, we aimed to evaluate the COVID-19 severity in AxSpAs receiving sulfasalazine and biologic-agent. Materials and Methods A total of 219 SARS-CoV-2 positive AxSpA patients were retrospectively analyzed. COVID-19 pneumonia, hospitalization rate, and length of stay were used to determine COVID-19 severity. AxSpA patients were mainly grouped and compared as sulfasalazine and non-sulfasalazine. Afterward, we excluded no-treatment patients to reveal the drug’s effects more clearly and regrouped AxSpA patients as sulfasalazine-monotherapy (34.3%), biologic-monotherapy (33.7%), and sulfasalazine + biologic (7.3%). Results Fifty-nine percent of the patients were male and the mean age was 45.0 years. Peripheral arthritis was 35% and uveitis 15%. In total, 41.5% of them have received sulfasalazine and 41.0% biologic agents, and the remaining patients with no AxSpA-specific treatment. In the first comparison, the sulfasalazine group had a higher age, more frequent COVID-19 pneumonia, hospitalization, and longer hospitalization than a non-sulfasalazine group. In the pairwise comparison of 3 treatment groups, the demographic and clinical features, the hospitalization rate and the length of hospital stay were similar but the sulfasalazine-monotherapy group had a higher frequency of COVID-19 pneumonia than the biologic-monotherapy group (23% vs. 7%, p = 0.008). Conclusion Our results imply sulfasalazine may be related to more severe COVID-19 in AxSpA patients. These patients should be followed more carefully in the presence of COVID-19, regardless of reasons such as age, comorbidity, and extra-axial disease, and consideration of discontinuing sulfasalazine maybe even thought.

OUTCOME OF DOUBLE BLIND COMPARATIVE STUDY OF SULFASALAZINE AND HYDROXYCHLOROQUINE IN EARLY UNDIFFERENTIATED INFLAMMATORY ARTHRITIS

Objective:Undifferentiated inflammatory arthritis is one of the requirements for being diagnosed in the patient doesnt meet the classical criteria for recognized arthritis. which no approved treatment algorithm exist. Sulfasalazine and hydroxychloroquine used in this trial for early Undifferentiated inflammatory arthritis. Methods: A six-month, double-blind, randomized experiment was conducted. Undifferentiated arthritis in 100 consecutive patients. ESR, morning stiffness, number of swollen joints, and a pain score are all measured on a monthly basis. Patients with certain rheumatological diagnoses were excluded.. Results: The trial was completed by 74 patients.The sulfasalazine group patient responds better and more promptly. There have been respond in terms of grip strength, pain score, and the duration of morning stiffness compared to hydroxychloroquine.The 26 withdrawal from the research prematurely owing to side effects, with gastrointestinal symptoms being the primary cause in the actively treated group. Conclusions:Our statistics lead us to the conclusion that sulfasalazine provides an earlier and better response than hydroxychloroquine. The earlier Response to sulfasalazine is a significant benefit for patients quality of life.