Synergistic Potential of Thymoquinone and Caffeic Acid in Experimental Ulcerative Colitis: A Biochemical and Histopathological Investigation

Synergistic Potential of Thymoquinone and Caffeic Acid in Experimental Ulcerative Colitis: A Biochemical and Histopathological Investigation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Synergistic Potential of Thymoquinone and Caffeic Acid in Experimental Ulcerative Colitis: A Biochemical and Histopathological Investigation Can Ersak, Ender Ergüder, B.Imge Erguder, Saygin Altiner, M. Recep Pekcici This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5815391/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim This study aims to model ulcerative colitis in rats using acetic acid and monitor colitis development with the "Disease Activity Index (DAI)." Additionally, the clinical, biochemical, and histopathological effects of thymoquinone (TQ) and caffeic acid phenethyl ester (CAPE) on this model are examined. Materials and Methods The study used 40 male Wistar Albino rats, weighing between 190–303 grams. The rats were divided into five groups of 8 each: Group 1 (Control) received intraperitoneal 0.9% saline solution for 5 days; Group 2 (Colitis) received acetic acid to induce colitis and 10% ethanol solution intraperitoneally for 5 days; Group 3 (TQ) received acetic acid to induce colitis and intraperitoneal thymoquinone (10 mg/kg/day) for 5 days; Group 4 (CAPE) received acetic acid to induce colitis and intraperitoneal caffeic acid (10 micromol/kg/day) for 5 days; Group 5 (TQ + CAPE) received acetic acid to induce colitis and intraperitoneal thymoquinone and caffeic acid for 5 days. On the 5th day, rats underwent laparotomy under anesthesia, colectomy was performed, and colon samples were taken for biochemical and histological analysis. Serum samples were also collected for biochemical analysis. Results Significant differences were observed in the Disease Activity Index, TNF-α, catalase, glutathione peroxidase, IL-10, and MDA, indicating a balance between oxidant and antioxidant parameters. CAPE was found to have a higher anti-inflammatory effect than TQ histopathologically. The combined application of CAPE and TQ showed a synergistic effect, reducing oxidative stress markers and enhancing antioxidant levels. Conclusion The hypothesis of this study is that CAPE and TQ will effectively reduce inflammation in an experimental colitis model induced by acetic acid. The results largely support this hypothesis, showing that CAPE has a higher anti-inflammatory efficacy than TQ and that their combined use is more effective in reducing inflammation. These findings suggest that CAPE and TQ could be a potential combination for colitis treatment and should be considered for clinical applications. This study provides new insights into the use of anti-inflammatory agents in experimental colitis models and highlights the potential advantages of combining CAPE and TQ in clinical settings. Ulcerative Colitis Thymoquinone Caffeic Acid Phenetyl Ester Experimental 1. Introduction Thymoquinone (TQ), the most abundant component of Nigella sativa (black cumin) seed oil, is attributed with many of the plant’s therapeutic properties. TQ has been studied for its wide range of pharmacological effects, including antioxidant, anti-inflammatory activities. It is also known for its gastroprotective and hepatoprotective properties. Literature suggests that TQ has a low side effect profile with no significant toxicity 1 . Caffeic acid phenethyl ester (CAPE) is a natural bioactive compound, commonly extracted from propolis, a bee product. CAPE has been shown to be effective against various conditions such as infections, oxidative stress, inflammation, cancer, diabetes, neurodegeneration, and anxiety 2 . In this study, acetic acid-induced colitis was used to model ulcerative colitis in rats, with disease progression monitored through the Disease Activity Index (DAI). The aim was to investigate the clinical, biochemical, and histopathological effects of TQ and CAPE on colitis. 2. Material and method The study was approved by the Ethics Committee of an institute accredited by the Turkish Ministry of Health. During the experiment and its termination, full compliance was ensured with the standards recommended by the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. The experimental animals were obtained from the Saki Yenili Experimental Animals Research Center. For the experiment conducted at the Health Sciences university, Ankara Training and Research Hospital Hüsnü Sakal Experimental and Clinical Research Center, 40 male Wistar Albino rats, weighing between 190–303 grams (with an average weight of 247.1 grams), were used. The animals were divided into 5 groups, with 8 animals in each group. 1) Pharmacological agents Acetic Acid (CH₃COOH) (Glacial 99–100%) was obtained from Tekkim Chemical Industry and Trade Limited Company. CAPE (CAS: 331-39-5) was supplied by Merck Chem. through Sigma-Aldrich Chemie GmbH. TQ (CAS: 490-91-5) was also obtained from Merck Chem. through Sigma-Aldrich Chemie GmbH. Experimental Protocol A 4% acetic acid solution was administered rectally using a feeding catheter, followed by a saline enema after 5 minutes to induce colitis. 2) Groups Group 1 (Control): 8 rats received 1 mL intraperitoneal (IP) 0.9% saline once daily for 5 days. Group 2 (Colitis): 8 rats were induced with colitis using acetic acid on day 1 and given 0.5 mL IP 10% ethanol solution daily for 5 days. Group 3 (TQ): 8 rats were induced with colitis on day 1 and received 10 mg/kg/day thymoquinone (TQ) IP daily for 5 days. Group 4 (CAPE): 8 rats were induced with colitis on day 1 and received 10 µmol/kg/day caffeic acid phenethyl ester (CAPE) IP, dissolved in 10% ethanol, daily for 5 days. Group 5 (TQ + CAPE): 8 rats were induced with colitis on day 1 and received both TQ (10 mg/kg/day) and CAPE (10 µmol/kg/day, dissolved in 10% ethanol) IP daily for 5 days. At the end of day 5, a laparotomy was performed on the subjects under anesthesia, and a colectomy was conducted. The removed colon samples were prepared for biochemical and histological analysis. Serum samples were also collected from the subjects for biochemical analysis. An independent researcher, blinded to group details, assessed the subjects daily for weight loss, stool consistency, and rectal bleeding. Weight loss was scored based on percentage loss: 0 for no loss, 1 for 1–5%, 2 for 5–10%, 3 for 10–15%, and 4 for more than 15%. Stool consistency was evaluated with 0 indicating normal stools, 2 for loose stools that did not adhere to the anus, and 4 for diarrhea adhering to the anus. Rectal bleeding was scored as 0 for no bleeding, 2 for occult blood positive, and 4 for visible hemorrhage adhering to the anus. Occult blood in the stool was detected using the Gikan card test and evaluated by the Guaiac method. 3) Biochemical analysis Tissue samples were frozen at -80°C until analysis. For tissue homogenization, samples were mixed with saline (1 g tissue/5 mL SF) and processed using a Bullet Blender homogenizer. Homogenates were centrifuged at 5000 rpm for 20 minutes at 4°C, and supernatants were collected for biochemical assays. Blood samples were centrifuged at 3500 rpm for 5 minutes at 4°C, and serum was stored at -80°C. IL-10 and TNF-alpha levels were measured using ELISA kits (Cloud-Clone Corp) following the manufacturer’s protocol. Caspase-3 was also quantified using a sandwich ELISA method. Additional biochemical parameters such as MDA, catalase, GPx, SOD, XO, and NO were measured spectrophotometrically at 532 nm, 240 nm, 340 nm, 560 nm, 290 nm, and 540 nm, respectively. 4) Histopathology assessment Total colon samples were fixed in formalin, embedded in paraffin, and sectioned at 4 µm thickness. Hematoxylin-eosin (HE) staining was performed, and the samples were examined using a ZEIS light microscope. Histological colitis damage scores were evaluated based on Dieleman’s scoring system, assessing inflammation severity, extent, and crypt damage. Inflammation was scored from 0 to 3, crypt damage from 0 to 4, with percentage involvement recorded. The data were analyzed using IBM SPSS V23. The normality of the data distribution was assessed using the Shapiro-Wilk test. For comparisons of normally distributed data across three or more groups, One-Way ANOVA was employed, with post-hoc analyses conducted using Tukey's test. For non-normally distributed data across three or more groups, the Kruskal-Wallis H test was used, followed by multiple comparisons with Dunn's test. Categorical data were compared using the Fisher-Freeman-Halton test. Results were presented as frequency (percentage) for categorical variables, and as mean ± standard deviation or median (minimum – maximum) for quantitative variables. A significance level of p < 0.050 was considered statistically significant 3. Results Comparative analysis of the Disease Activity Index (DAI) showed significant differences in median weight scores across groups (p = 0.003). The SF group had a median score of 0, while the Ethanol, TQ, CAPE, and CAPE + TQ groups had scores of 1, 1, 1, and 1.5, respectively. Stool consistency also differed significantly (p = 0.005), with scores of 0 in the SF group, and 8, 4, 4, and 5 in the Ethanol, TQ, CAPE, and CAPE + TQ groups, respectively. Rectal bleeding showed significant differences (p = 0.027), with the SF group scoring 0 and the Ethanol, TQ, CAPE, and CAPE + TQ groups scoring 7, 1, 3, and 3, respectively. Total DAI scores were significantly different (p = 0.001), with medians of 0, 16.5, 10, 9, and 9.5 for the SF, Ethanol, TQ, CAPE, and CAPE + TQ groups, respectively. Table 1. Dissease Activity Index Scores Across the Groups Saline Ethanol-Colitis TQ- Colitis CAPE- Colitis CAPE + TQ-Colitis Total Test statistics p* Weight Score 0 ± 0 1,5 ± 0,76 1 ± 0,53 1,5 ± 1,69 1,5 ± 0,93 1,1 ± 1,08 16,299 0,003 0 (0–0) b 1 (1–3) a 1 (0–2) ab 1 (0–4) ab 1,5 (0–3) a 1 (0–4) Consistency Score 1 ± 1,51 8,25 ± 3,28 5,25 ± 5,23 5,5 ± 4,63 5 ± 2,39 5 ± 4,2 14,774 0,005 0 (0–4) b 8 (6–16) a 4 (0–14) ab 4 (0–12) ab 5 (2–8) ab 4 (0–16) Bleeding Score 0 ± 0 6,75 ± 4,4 3,75 ± 4,71 4,5 ± 5,1 4,75 ± 5,23 3,95 ± 4,7 10,977 0,027 0 (0–0) b 7 (0–14) a 1 (0–10) ab 3 (0–14) ab 3 (0–12) ab 2 (0–14) DAI Total 1 ± 1,51 16,5 ± 5,29 10 ± 8,3 11,5 ± 8,82 11,25 ± 7,48 10,05 ± 8,24 19,169 0,001 0 (0–4) b 16,5 (9–23) a 10 (0–26) ab 9 (3–30) a 9,5 (3–22 )a 8,5 (0–30) In colon tissue analysis, IL-10 levels varied significantly between groups (p=0.002), with the SF group showing a median of 141.14, while the Ethanol, TQ, CAPE, and CAPE+TQ groups had values of 137.79, 76.01, 80.32, and 78.17, respectively. Catalase (CAT) activity was significantly higher in the TQ, CAPE, and CAPE+TQ groups compared to the Ethanol group (p=0.001). GSH-Px levels also differed significantly between groups (p=0.003). Serum TNF-alpha levels showed significant variation (p=0.002), with higher levels in the SF group compared to CAPE and CAPE+TQ groups. Caspase-3, MDA, and CAT levels were significantly different between the SF, TQ, CAPE, and CAPE+TQ groups. NOS levels varied significantly (p=0.013), but no significant differences were found in multiple comparisons. Group Total Test statistics p Intraperitoneal administration of saline (SF) was applied Colitis was induced, and intraperitoneal ethanol was administered Colitis was induced, and intraperitoneal TQ was administered Colitis was induced, and intraperitoneal CAPE was administered Colitis was induced, and intraperitoneal CAPE+TQ were administered TNF alfa 60,7 ± 17,91 41,96 ± 26,29 45,43 ± 13,86 44,21 ± 15,89 43,54 ± 9,93 47,17 ± 18,09 4,466 0,347** 55,75 (43,27 - 93) 50,57 (11,2 - 69,57) 45,29 (26,69 - 67,86) 43,62 (14,7 - 64,92) 42,73 (32,38 - 63,15) 46,6 (11,2 - 93) IL10 143,67 ± 43,77 153,53 ± 47,9 81,01 ± 41,16 88,21 ± 36,51 81,62 ± 32,97 109,61 ± 50,5 17,405 0,002** 141,14 (95,09 - 231,22) ab 137,79 (106,52 - 259,2) b 76,01 (32,92 - 157,32) a 80,32 (43,22 - 134,81) ab 78,17 (37,24 - 129,63) a 106,45 (32,92 - 259,2) Caspase3 1,05 ± 0,54 1,09 ± 0,72 1,16 ± 0,47 0,87 ± 0,36 0,8 ± 0,37 1 ± 0,5 3,407 0,492** 0,77 (0,6 - 2,16) 0,84 (0,44 - 2,75) 1,09 (0,78 - 2,21) 0,93 (0,12 - 1,39) 0,78 (0,07 - 1,31) 0,85 (0,07 - 2,75) MDA 16,37 ± 0,67 15,96 ± 2,04 14,55 ± 4,3 16,38 ± 1,48 15,97 ± 0,96 15,85 ± 2,28 0,535 0,712* 16,5 (15,48 - 17,1) 16,29 (12,98 - 18,31) 15,61 (6,37 - 19,84) 15,89 (14,92 - 18,79) 15,69 (14,6 - 17,34) 15,93 (6,37 - 19,84) CAT 117,66 ± 39,51 bc 101 ± 28,1 b 158,5 ± 41,03 ac 154,09 ± 38,92 ac 172,56 ± 13,35 a 140,76 ± 42,07 6,318 0,001* 118,55 (58,6 - 197,6) 106,85 (51,2 - 130,3) 150,8 (115,7 - 224) 147,85 (106,9 - 213,7) 173,5 (152,3 - 193,2) 128,85 (51,2 - 224) GSH-Px 0,36 ± 0,01 0,4 ± 0,04 0,36 ± 0,03 0,43 ± 0,05 0,41 ± 0,05 0,39 ± 0,05 16,161 0,003** 0,35 (0,34 - 0,39) b 0,39 (0,35 - 0,49) ab 0,36 (0,29 - 0,4) ab 0,43 (0,36 - 0,5) a 0,43 (0,35 - 0,47) ab 0,38 (0,29 - 0,5) SOD 105,14 ± 15,32 77,9 ± 30,5 107,93 ± 12,94 110,08 ± 37,4 97,96 ± 7,4 99,8 ± 25,3 8,007 0,091** 106,1 (84,8 - 129,3) 78,95 (28,2 - 122,4) 113,15 (89,5 - 123) 102,5 (78,8 - 200) 95,9 (90,3 - 109,8) 99,9 (28,2 - 200) XO 0,02 ± 0,03 0 ± 0 0,01 ± 0,03 0,03 ± 0,08 0 ± 0 0,01 ± 0,04 4,283 0,369** 0 (0 - 0,07) 0 (0 - 0) 0 (0 - 0,07) 0 (0 - 0,22) 0 (0 - 0,01) 0 (0 - 0,22) NO 106,31 ± 76,21 70,47 ± 50,12 62,59 ± 34,97 109,25 ± 42,92 69,94 ± 16,27 83,71 ± 49,96 5,206 0,267** 91,75 (25 - 268) 58,88 (10 - 167,25) 56,63 (6,5 - 113,75) 100,63 (53,75 - 169,75) 62,38 (53 - 91) 76,5 (6,5 - 268) NOS 11,78 ± 1,76 10,83 ± 2,05 11,96 ± 1,53 11,78 ± 1,48 10,61 ± 1,64 11,39 ± 1,71 1,061 0,390* 12,32 (8,96 - 13,69) 11,33 (6,49 - 13,24) 12,1 (9,56 - 13,99) 11,29 (9,79 - 13,76) 10,26 (8,96 - 14,06) 11,38 (6,49 - 14,06) *One-Way ANOVA test; * Kruskal-Wallis H test; a-c : There is no significant difference between groups with the same letter; Mean ± Standard Deviation; Median (Minimum – Maximum) Table 2. Comparison of Quantitative Parameters in Tissue by Groups Group Total Test statistics p Intraperitoneal administration of saline (SF) was applied Colitis was induced, and intraperitoneal ethanol was administered Colitis was induced, and intraperitoneal TQ was administered Colitis was induced, and intraperitoneal CAPE was administered Colitis was induced, and intraperitoneal CAPE+TQ were administered TNF alfa 100,16 ± 21,99 b 71,18 ± 18,15 ab 79,07 ± 27,19 ab 61,51 ± 14,57 a 53,37 ± 24,28 a 73,06 ± 26,23 5,501 0,002* 102,41 (54,84 - 129,86) 75,39 (36,36 - 88,71) 81,51 (41,53 - 127,1) 59,77 (43,21 - 91,65) 46,82 (32,51 - 96,01) 70,47 (32,51 - 129,86) Caspase3 1,14 ± 0,17 1,49 ± 0,44 1,55 ± 0,64 1,81 ± 0,54 2,44 ± 1,08 1,69 ± 0,75 14,497 0,006** 1,13 (0,86 - 1,38) b 1,31 (1,2 - 2,47) ab 1,47 (1,02 - 3,02) ab 1,69 (1,06 - 2,66) ab 2,27 (1,05 - 4,17) a 1,45 (0,86 - 4,17) MDA 16,32 ± 1,06 12,28 ± 3,99 12,02 ± 3,68 14,8 ± 1,31 11,47 ± 4,05 13,38 ± 3,51 15,349 0,004** 16,49 (14,52 - 17,82) b 13,95 (5,65 - 15,57) ab 12,83 (6,53 - 17,42) a 14,8 (12,58 - 16,78) ab 11,17 (3,15 - 16,21) a 14,28 (3,15 - 17,82) CAT 2,76 ± 2,11 2,76 ± 1,64 4,4 ± 2,71 10,06 ± 9,73 13,9 ± 3,33 6,78 ± 6,48 20,407 <0,001** 1,5 (1,5 - 7,3) b 2,2 (1,5 - 5,9) b 3,65 (1,5 - 8,8) ab 5,85 (1,5 - 26,4) ab 13,2 (10,2 - 19) a 4,4 (1,5 - 26,4) GSH-Px 0,16 ± 0,02 0,17 ± 0,02 0,18 ± 0,03 0,16 ± 0,05 0,14 ± 0,06 0,16 ± 0,04 1,441 0,241* 0,16 (0,13 - 0,18) 0,17 (0,12 - 0,19) 0,18 (0,15 - 0,25) 0,17 (0,08 - 0,24) 0,16 (0 - 0,19) 0,16 (0 - 0,25) SOD 60,95 ± 10,63 67,41 ± 10,86 121,21 ± 157,28 59,39 ± 13,54 60,85 ± 6,54 73,96 ± 71,43 3,894 0,421** 62,8 (43,3 - 75) 69,25 (50,4 - 78,2) 66,95 (53,2 - 509,7) 64,55 (31,2 - 70,8) 61,15 (50,2 - 68,7) 65,2 (31,2 - 509,7) XO 0,09 ± 0,03 0,07 ± 0,04 0,06 ± 0,02 0,07 ± 0,04 0,06 ± 0,04 0,07 ± 0,04 4,16 0,385** 0,09 (0,02 - 0,14) 0,09 (0 - 0,11) 0,06 (0,04 - 0,1) 0,08 (0 - 0,11) 0,05 (0 - 0,12) 0,08 (0 - 0,14) NO 18,72 ± 11,01 19,16 ± 5,85 21,78 ± 11,78 20,56 ± 9,19 23,18 ± 11,81 20,62 ± 9,72 1,337 0,855** 17,38 (10,25 - 44) 19,88 (11,75 - 30) 16,75 (11,75 - 44) 20,75 (7,25 - 33,5) 18,5 (12,5 - 44,25) 18,5 (7,25 - 44,25) NOS 9,45 ± 3,75 9,41 ± 2,2 9,49 ± 1,99 16,3 ± 6,45 17,77 ± 8,31 12,35 ± 6,06 12,686 0,013** 7,65 (6,98 - 17,55) 9,23 (7,16 - 14,06) 9,81 (6,6 - 12,11) 15,51 (7,54 - 27,64) 20,66 (4,5 - 28,01) 10,24 (4,5 - 28,01) *One-Way ANOVA test; * Kruskal-Wallis H test ; a-b : There is no significant difference between groups with the same letter; Mean ± Standard Deviation; Median (Minimum – Maximum) Table 3. Comparison of Quantitative Parameters in Serum by Group Histopathological analysis revealed statistically significant relationships between the groups and various parameters of inflammation. In terms of inflammation severity, the control group had mostly no inflammation (62.5%), while the ETH, TQ, CAPE, and CAPE + TQ groups showed increasing levels of mild to severe inflammation, with a significant group effect (p = 0.011). Regarding the spread of inflammation, the control group had no spread in 62.5% of the cases, whereas the ETH, TQ, CAPE, and CAPE + TQ groups exhibited mucosal to transmural involvement, with a statistically significant difference between the groups (p = 0.016). Crypt damage also showed a significant group effect (p = 0.025), with the control group displaying minimal damage and the experimental groups showing varying degrees of basal damage and crypt loss. Additionally, the percentage of colonic involvement was significantly related to the group (p = 0.017), with higher levels of involvement observed in the ETH, TQ, CAPE, and CAPE + TQ groups compared to the control. Despite these significant associations, post-hoc comparisons did not reveal any specific differences between the groups. There is a statistically significant difference in the median total scores among the groups (p = 0.004). The median total score was 0 in the control group, 7.5 in the ETH group, 6.5 in the TQ group, 4 in the CAPE group, and 5 in the CAPE + TQ group. The control group showed significant differences compared to the ETH and TQ groups. Table 4 Comparison of Categorical Pathological Scores by Group Group Test statistics p* Saline ETH TQ CAPE CAPE + TQ Inflammation Score None 5 (62,5) 0 (0) 0 (0) 0 (0) 0 (0) 20,497 0,011 Mild 3 (37,5) 3 (37,5) 3 (37,5) 6 (75) 5 (62,5) Moderate 0 (0) 3 (37,5) 4 (50) 2 (25) 1 (12,5) Severe 0 (0) 2 (25) 1 (12,5) 0 (0) 2 (25) Spread of Inflammation None 5 (62,5) 0 (0) 0 (0) 0 (0) 0 (0) 19,824 0,016 Mucosa 3 (37,5) 3 (37,5) 5 (62,5) 6 (75) 3 (37,5) Submucosa 0 (0) 2 (25) 2 (25) 1 (12,5) 4 (50) Transmural 0 (0) 3 (37,5) 1 (12,5) 1 (12,5) 1 (12,5) Cyrpt Damage No Damage 5 (62,5) 0 (0) 0 (0) 0 (0) 0 (0) 21,78 0,025 Basal 1/3 damaged 2 (25) 4 (50) 4 (50) 6 (75) 6 (75) Basal 2/3 damaged 1 (12,5) 3 (37,5) 3 (37,5) 2 (25) 1 (12,5) Cyrpt 0 (0) 0 (0) 0 (0) 0 (0) 1 (12,5) Loss of crypt and surface ephitelium 0 (0) 1 (12,5) 1 (12,5) 0 (0) 0 (0) Percentage Involvement %0 5 (62,5) 0 (0) 0 (0) 0 (0) 0 (0) 22,767 0,017 %1–25 3 (37,5) 2 (25) 3 (37,5) 6 (75) 6 (75) %25–50 0 (0) 3 (37,5) 3 (37,5) 1 (12,5) 1 (12,5) %51–75 0 (0) 2 (25) 1 (12,5) 1 (12,5) 1 (12,5) %76–100 0 (0) 1 (12,5) 1 (12,5) 0 (0) 0 (0) Total Test Statistics p* Mean ± S.Deviation Median (Min-Max) Group Saline 1,63 ± 2,26 0 (0–5) b 15,606 0,004 ETH 7,88 ± 3,44 7,5 (4–14) a TQ 7 ± 3,16 6,5 (4–14) a CAPE 5,25 ± 2,31 4 (4–9) ab CAPE + TQ 6,13 ± 2,8 5 (4–11) ab Total 5,58 ± 3,46 4,5 (0–14) *Kruskal-Wallis H test; ** a−b : There is no significant difference between groups with the same letter. Table 5. Comparison of Total Scores by Group 4. Discussion The Disease Activity Index (DAI) was used to evaluate colitis activity and symptoms, a scoring system first validated by Murthy et al. 3 . Daily DAI assessments were performed by an independent researcher, and the ethanol-colitis group had the highest median score (16.5), indicating the most severe colitis symptoms. The high DAI scores in the ethanol-colitis models compared to the SF group confirmed the appropriate induction of colitis. The DAI total scores in the TQ, CAPE, and CAPE + TQ groups were significantly lower than those in the ethanol-colitis group, and the differences were statistically significant. Similar differences were observed across weight, consistency, and bleeding scores among the groups. The significant results of the disease activity index scores indicate that the colitis model induced in the subjects was successful. Tissue TNF-alpha levels were lowest in the CAPE + TQ group, while the ethanol-colitis group had the highest quantitative TNF-alpha levels, although the differences between groups were not statistically significant. In serum, the differences in TNF-alpha levels were statistically significant (p = 0.002), with the lowest levels observed in the CAPE and CAPE + TQ groups, which were significantly lower than in the ethanol-colitis group. This suggests a potential synergistic anti-inflammatory effect when TQ and CAPE are used together. Currently, anti-TNF drugs are used in the treatment of ulcerative colitis, offering an alternative for steroid-resistant cases, while effectively preventing relapses and reducing colectomy rates. In this context, further clinical studies on the antioxidant properties of TQ and CAPE molecules could be beneficial for improving UC prognosis 4 , 5 . Regarding IL-10 levels in tissue, the ethanol-colitis group had a median of 137.79, compared to 76.01 in the TQ group, 80.32 in the CAPE group, and 78.17 in the CAPE + TQ group. The differences between the ethanol-colitis group and the TQ, CAPE, and CAPE + TQ groups were statistically significant (p = 0.002). The high IL-10 levels in colitis-induced rats align with findings in the literature, suggesting a response to high cytokine secretion. In our study, the elevated IL-10 levels observed in the colitis-induced subjects align with findings in the literature. A study by Fonseca et al. reported higher IL-10 producing cells in ulcerative colitis (UC) patients compared to healthy individuals. IL-10 was concentrated in macrophages and lymphocytes and spread across a wide area from the serosa to the mucosal layer. All biopsies showed increased IL-10-reactive cells in the colon serosa 6 . Melgar et al. also demonstrated increased IL-10 mRNA levels and IL-10 positive cells in UC patients' T-lymphocytes. These findings support that the elevated IL-10 levels in our study reflect an inflammatory response consistent with UC pathophysiology 7 . Tissue catalase levels also showed significant differences (p = 0.001), with the CAPE + TQ group having the highest levels, suggesting a synergistic effect in enhancing antioxidant activity. Serum catalase levels were significantly different as well (p < 0.001), with CAPE + TQ showing the highest levels, further supporting a positive synergistic effect. In a study by Rana et al., serum catalase levels were compared between UC patients in remission and those with active colitis, showing significantly higher catalase levels in the active colitis group 8 . Catalase plays a crucial role in eliminating hydrogen peroxide, and novel agents mimicking SOD and catalase are being explored as potential treatments for UC. Zhang et al. designed a nanosystem (Tpl/OxbCD NP) that effectively eliminates ROS components by mimicking SOD and catalase functions 9 . Based on this, catalase-mimicking molecules are gaining attention in UC treatment. Our study suggests that the potential anti-inflammatory effects of thymoquinone and CAPE may be linked to increased endogenous catalase levels. The difference in catalase levels between the SF group and the CAPE + TQ group suggests a synergistic effect of combined treatment on catalase activity. For GSH-Px, statistically significant differences were found in tissue levels (p = 0.003), with higher levels in the CAPE and CAPE + TQ groups compared to the SF group. However, serum GSH-Px levels did not show significant differences. Tissue and serum SOD levels were not statistically significant across groups, although CAPE and TQ groups had higher quantitative levels. In a study by Okutan et al. on diabetic rat hearts, CAPE administration was examined for its effects on the oxidative/antioxidative balance. While GSH-Px activity did not differ between diabetic rats and controls, it was significantly higher in CAPE-treated subjects. This suggests, consistent with our study, that CAPE may positively influence GSH-Px activity, independent of the underlying pathological condition 10 . Serum caspase-3 levels showed statistically significant differences (p = 0.006), with the highest levels in the CAPE + TQ group, suggesting a possible involvement in the anti-inflammatory mechanisms of these agents. A study by Qi TY et al. demonstrated that apoptosis induced by visilizumab increases apoptosis in activated T-lymphocytes, reducing inflammation in the colonic lamina propria and facilitating rapid remission in ulcerative colitis 11 . Similarly, Shteingart et al. showed that inhibiting the caspase-3 mechanism leads to defective T-lymphocyte responses, triggering inflammation. In our study, the observed increase in serum caspase-3 levels in the CAPE, TQ, and CAPE + TQ groups raises the question of whether these agents may operate through novel anti-inflammatory mechanisms, which warrant further investigation at the cellular level 12 . New studies are needed to elucidate the precise mechanisms behind their anti-inflammatory effects. Serum MDA levels were significantly different (p = 0.004), with lower levels in the TQ and CAPE + TQ groups compared to the ethanol-colitis group, indicating a protective effect of these molecules against oxidative damage. In a study by Kruidenier et al., investigating the relationship between oxidative damage and inflammatory bowel disease (IBD) at the cellular level, MDA levels were found to be significantly higher in the active inflammation group of ulcerative colitis (UC) patients compared to those without inflammation and the control group 13 . This finding aligns with our study, where the lowest serum MDA levels were observed in the CAPE + TQ group, suggesting that these two agents may have protective effects against oxidative damage to cell membranes. There were no significant differences in XO levels between groups, consistent with previous studies suggesting XO may not be the primary source of superoxide production in colitis 14 . Serum NOS levels showed a significant difference (p = 0.013), with higher levels in the CAPE + TQ group, which, combined with lower clinical and histopathological inflammation scores, suggests a protective role of NOS in colon structure. However, more detailed studies are needed to fully understand the mechanisms. A study on ulcerative colitis patients found that nitric oxide (NO) levels were significantly higher in the rectal dialysate of patients with active colitis 15 . However, the use of NOS inhibitors in experimental colitis models has yielded inconsistent results. Non-specific NOS inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), reduced intestinal inflammation in some models, but in others, they either provided no protection or worsened inflammation 16 , 17 . In a study by McCafferty et al., rats genetically unable to produce NOS were compared with normal rats after acetic acid-induced colitis, showing more severe inflammation in the NOS-deficient group 18 . In our study, CAPE + TQ-treated subjects exhibited higher NOS levels and lower clinical and histopathological inflammation scores, suggesting a protective role of NOS and NO in maintaining colon cell structure. However, further research is needed to explore the underlying cellular mechanisms in detail. Histopathological analysis revealed statistically significant differences in total inflammation scores among the groups (p = 0.004). The median score in the SF group was 0, while it was 7.5 in the ethanol-colitis group, 6.5 in the TQ group, 4 in the CAPE group, and 5 in the CAPE + TQ group. There was a significant difference between the SF group and the ethanol-colitis and TQ groups. CAPE and CAPE + TQ showed no significant difference from the SF group, suggesting that the combination of CAPE and TQ may have stronger anti-inflammatory effects than TQ alone. In a study by Mahgoub, rats pre-treated with 10 mg/kg oral thymoquinone (TQ) for three days prior to acetic acid-induced colitis showed lower levels of inflammation in colon specimens compared to the colitis-only group 19 . This suggests that, in addition to its anti-inflammatory effect, TQ may offer protective benefits in colitis. Similarly, in our study, CAPE administered intraperitoneally after the onset of acute colitis was found to be more effective in reducing inflammation, as observed in histopathological examinations. Tambuwala et al. also demonstrated that CAPE reduced fibrosis at the cellular level in a DSS-induced chronic colon inflammation model 20 . Our results further confirm the anti-inflammatory efficacy of CAPE in acute colitis. 5. Conclusion The hypothesis of our study is that CAPE and thymoquinone (TQ) would effectively reduce inflammation in an acetic acid-induced colitis model. Our findings largely support this hypothesis, with histopathological analysis indicating that CAPE demonstrates slightly stronger anti-inflammatory effects than TQ. Notably, the combination of CAPE and TQ showed synergistic potential, as evidenced by enhanced biochemical parameters, including oxidative stress markers and antioxidant levels. This synergistic effect suggests that the co-administration of CAPE and TQ may offer additional benefits in suppressing inflammatory processes. Our study is the first to compare and combine these two molecules in a colitis model, providing valuable insights for future therapeutic approaches. The results indicate that combining CAPE and TQ could be a more effective anti-inflammatory strategy for treating colitis, highlighting its potential for future clinical evaluation. These findings introduce a novel perspective on anti-inflammatory agents in experimental colitis models and suggest that the CAPE-TQ combination warrants further exploration in clinical settings. Declarations Acknowledgments The authors received no specific funding or assistance for this research. Ethical Consideratons This study was approved by the Local Ethics Committee of Ankara training and Research Hospital and Ministy of Health(meeting number: 0076, with decision number: 736, on August 10, 2023.). All experimental procedures were conducted in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes, ensuring the highest standards of animal welfare. References Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res . May-Jun 2015;95-96:138-58. doi:10.1016/j.phrs.2015.03.011 Murtaza G, Karim S, Akram MR, et al. Caffeic acid phenethyl ester and therapeutic potentials. Biomed Res Int . 2014;2014:145342. doi:10.1155/2014/145342 Murthy S, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Digestive diseases and sciences . 1993;38:1722-1734. Kornbluth A, Sachar DB, Gastroenterology PPCotACo. Ulcerative colitis practice guidelines in adults: American college of gastroenterology, practice parameters committee. Official journal of the American College of Gastroenterology| ACG . 2010;105(3):501-523. D'haens GR, Panaccione R, Higgins PD, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Official journal of the American College of Gastroenterology| ACG . 2011;106(2):199-212. Fonseca-Camarillo G, Furuzawa-Carballeda J, Llorente L, Yamamoto-Furusho JK. IL-10—and IL-20—expressing epithelial and inflammatory cells are increased in patients with ulcerative colitis. Journal of clinical immunology . 2013;33:640-648. Melgar S, Yeung MM, Bas A, et al. Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis. Clinical & Experimental Immunology . 2003;134(1):127-137. Rana SV, Sharma S, Prasad KK, Sinha SK, Singh K. Role of oxidative stress & antioxidant defence in ulcerative colitis patients from north India. Indian Journal of Medical Research . 2014;139(4):568-571. Shen X, Shi R, Zhang H, Li K, Zhao Y, Zhang R. The Toll-like receptor 4 D299G and T399I polymorphisms are associated with Crohn’s disease and ulcerative colitis: a meta-analysis. 2010. p. 69-77. Okutan H, Ozcelik N, Yilmaz HR, Uz E. Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. Clinical Biochemistry . 2005;38(2):191-196. Qi TY, Saruta M, Papadakis KA. Visilizumab induces apoptosis of mucosal T lymphocytes in ulcerative colitis through activation of caspase 3 and 8 dependent pathways. Clinical Immunology . 2008;127(3):322-329. Shteingart S, Rapoport M, Grodzovski I, et al. Therapeutic potency of IL2–caspase 3 targeted treatment in a murine experimental model of inflammatory bowel disease. Gut . 2009;58(6):790-798. Kruidenier L, Kuiper I, Lamers CB, Verspaget HW. Intestinal oxidative damage in inflammatory bowel disease: semi‐quantification, localization, and association with mucosal antioxidants. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland . 2003;201(1):28-36. Reynolds P, Rhenius S, Hunter J. Xanthine oxidase activity is not increased in the colonic mucosa of ulcerative colitis. Alimentary pharmacology & therapeutics . 1996;10(5):737-741. Roediger W, Lawson M, Nance S, Radcliffe B. Detectable colonic nitrite levels in inflammatory bowel disease–mucosal or bacterial malfunction? Digestion . 1986;35(4):199-204. Boughton-Smith N, Evans S, Whittle B, et al. Nitric oxide synthase activity in ulcerative colitis and Crohn's disease. The Lancet . 1993;342(8867):338-e2. Grisham MB, Specian RD, Zimmerman TE. Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis. Journal of Pharmacology and Experimental Therapeutics . 1994;271(2):1114-1121. McCafferty DM, Mudgett JS, Swain MG, Kubes P. Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology . 1997;112(3):1022-1027. Mahgoub AA. Thymoquinone protects against experimental colitis in rats. Toxicology letters . 2003;143(2):133-143. Tambuwala MM, Kesharwani P, Shukla R, Thompson PD, McCarron PA. Caffeic acid phenethyl ester (CAPE) reverses fibrosis caused by chronic colon inflammation in murine model of colitis. Pathology-Research and Practice . 2018;214(11):1909-1911. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5815391","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":402509908,"identity":"6b2ee0c0-e123-4a10-894d-3d3ece192ed8","order_by":0,"name":"Can Ersak","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYDCCAzAGDzOIKSFDiha2BJAWHlK08BiAKYI6+G4ffvi5oOKePX/Pmc+vbtRY8DCwHz66AZ8WyXNpxtIzzhQnzjjbu8065xjQYTxpaTfwaTE4w8MgzduWkMBwnnebcQ4bUIsEjxkhLcy/ef8l2Muf53lmnPOPOC1s0rwNCYwbzvYwP85tI0KL5Bk2M2ueYwmJG88cM2PO7ZPgYSPkF74zzI9v89Qk2MudSX78OedbnRw/++FjeLUgAzYJMEmschBg/kCK6lEwCkbBKBg5AACQgEUQT7+7gAAAAABJRU5ErkJggg==","orcid":"","institution":"Kızılcahamam State Hospital","correspondingAuthor":true,"prefix":"","firstName":"Can","middleName":"","lastName":"Ersak","suffix":""},{"id":402509909,"identity":"66d495b7-bc39-4fac-9321-05b8c77a3b39","order_by":1,"name":"Ender Ergüder","email":"","orcid":"","institution":"Health Sciences University","correspondingAuthor":false,"prefix":"","firstName":"Ender","middleName":"","lastName":"Ergüder","suffix":""},{"id":402509910,"identity":"ab2bbbd8-d153-4f9a-9d21-3cd5aff3b31f","order_by":2,"name":"B.Imge Erguder","email":"","orcid":"","institution":"Ankara University","correspondingAuthor":false,"prefix":"","firstName":"B.Imge","middleName":"","lastName":"Erguder","suffix":""},{"id":402509911,"identity":"bc7e3833-e904-4ac6-89aa-22fff9850ac7","order_by":3,"name":"Saygin Altiner","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Saygin","middleName":"","lastName":"Altiner","suffix":""},{"id":402509912,"identity":"c7e6f172-26f1-4ddf-8042-3f99b0e0fbff","order_by":4,"name":"M. Recep Pekcici","email":"","orcid":"","institution":"Health Sciences University","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"Recep","lastName":"Pekcici","suffix":""}],"badges":[],"createdAt":"2025-01-12 20:53:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5815391/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5815391/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74386101,"identity":"7abca310-9b60-47cd-b781-e2e38405dde7","added_by":"auto","created_at":"2025-01-21 20:16:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":860887,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5815391/v1/a1602126-4c35-4b9f-9c2b-43ee63abbdee.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synergistic Potential of Thymoquinone and Caffeic Acid in Experimental Ulcerative Colitis: A Biochemical and Histopathological Investigation","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThymoquinone (TQ), the most abundant component of Nigella sativa (black cumin) seed oil, is attributed with many of the plant\u0026rsquo;s therapeutic properties. TQ has been studied for its wide range of pharmacological effects, including antioxidant, anti-inflammatory activities. It is also known for its gastroprotective and hepatoprotective properties. Literature suggests that TQ has a low side effect profile with no significant toxicity\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCaffeic acid phenethyl ester (CAPE) is a natural bioactive compound, commonly extracted from propolis, a bee product. CAPE has been shown to be effective against various conditions such as infections, oxidative stress, inflammation, cancer, diabetes, neurodegeneration, and anxiety\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, acetic acid-induced colitis was used to model ulcerative colitis in rats, with disease progression monitored through the Disease Activity Index (DAI). The aim was to investigate the clinical, biochemical, and histopathological effects of TQ and CAPE on colitis.\u003c/p\u003e"},{"header":"2. Material and method","content":"\u003cp\u003e The study was approved by the Ethics Committee of an institute accredited by the Turkish Ministry of Health. During the experiment and its termination, full compliance was ensured with the standards recommended by the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. The experimental animals were obtained from the Saki Yenili Experimental Animals Research Center. For the experiment conducted at the Health Sciences university, Ankara Training and Research Hospital H\u0026uuml;sn\u0026uuml; Sakal Experimental and Clinical Research Center, 40 male Wistar Albino rats, weighing between 190\u0026ndash;303 grams (with an average weight of 247.1 grams), were used. The animals were divided into 5 groups, with 8 animals in each group.\u003c/p\u003e\n\u003ch3\u003e1) Pharmacological agents\u003c/h3\u003e\n\u003cp\u003eAcetic Acid (CH₃COOH) (Glacial 99\u0026ndash;100%) was obtained from Tekkim Chemical Industry and Trade Limited Company. CAPE (CAS: 331-39-5) was supplied by Merck Chem. through Sigma-Aldrich Chemie GmbH. TQ (CAS: 490-91-5) was also obtained from Merck Chem. through Sigma-Aldrich Chemie GmbH.\u003c/p\u003e \u003cp\u003eExperimental Protocol\u003c/p\u003e \u003cp\u003e A 4% acetic acid solution was administered rectally using a feeding catheter, followed by a saline enema after 5 minutes to induce colitis.\u003c/p\u003e\n\u003ch3\u003e2) Groups\u003c/h3\u003e\n\u003cp\u003eGroup 1 (Control): 8 rats received 1 mL intraperitoneal (IP) 0.9% saline once daily for 5 days.\u003c/p\u003e \u003cp\u003eGroup 2 (Colitis): 8 rats were induced with colitis using acetic acid on day 1 and given 0.5 mL IP 10% ethanol solution daily for 5 days.\u003c/p\u003e \u003cp\u003eGroup 3 (TQ): 8 rats were induced with colitis on day 1 and received 10 mg/kg/day thymoquinone (TQ) IP daily for 5 days.\u003c/p\u003e \u003cp\u003eGroup 4 (CAPE): 8 rats were induced with colitis on day 1 and received 10 \u0026micro;mol/kg/day caffeic acid phenethyl ester (CAPE) IP, dissolved in 10% ethanol, daily for 5 days.\u003c/p\u003e \u003cp\u003eGroup 5 (TQ\u0026thinsp;+\u0026thinsp;CAPE): 8 rats were induced with colitis on day 1 and received both TQ (10 mg/kg/day) and CAPE (10 \u0026micro;mol/kg/day, dissolved in 10% ethanol) IP daily for 5 days.\u003c/p\u003e \u003cp\u003eAt the end of day 5, a laparotomy was performed on the subjects under anesthesia, and a colectomy was conducted. The removed colon samples were prepared for biochemical and histological analysis. Serum samples were also collected from the subjects for biochemical analysis.\u003c/p\u003e \u003cp\u003eAn independent researcher, blinded to group details, assessed the subjects daily for weight loss, stool consistency, and rectal bleeding. Weight loss was scored based on percentage loss: 0 for no loss, 1 for 1\u0026ndash;5%, 2 for 5\u0026ndash;10%, 3 for 10\u0026ndash;15%, and 4 for more than 15%. Stool consistency was evaluated with 0 indicating normal stools, 2 for loose stools that did not adhere to the anus, and 4 for diarrhea adhering to the anus. Rectal bleeding was scored as 0 for no bleeding, 2 for occult blood positive, and 4 for visible hemorrhage adhering to the anus. Occult blood in the stool was detected using the Gikan card test and evaluated by the Guaiac method.\u003c/p\u003e\n\u003ch3\u003e3) Biochemical analysis\u003c/h3\u003e\n\u003cp\u003eTissue samples were frozen at -80\u0026deg;C until analysis. For tissue homogenization, samples were mixed with saline (1 g tissue/5 mL SF) and processed using a Bullet Blender homogenizer. Homogenates were centrifuged at 5000 rpm for 20 minutes at 4\u0026deg;C, and supernatants were collected for biochemical assays. Blood samples were centrifuged at 3500 rpm for 5 minutes at 4\u0026deg;C, and serum was stored at -80\u0026deg;C. IL-10 and TNF-alpha levels were measured using ELISA kits (Cloud-Clone Corp) following the manufacturer\u0026rsquo;s protocol. Caspase-3 was also quantified using a sandwich ELISA method. Additional biochemical parameters such as MDA, catalase, GPx, SOD, XO, and NO were measured spectrophotometrically at 532 nm, 240 nm, 340 nm, 560 nm, 290 nm, and 540 nm, respectively.\u003c/p\u003e\n\u003ch3\u003e4) Histopathology assessment\u003c/h3\u003e\n\u003cp\u003eTotal colon samples were fixed in formalin, embedded in paraffin, and sectioned at 4 \u0026micro;m thickness. Hematoxylin-eosin (HE) staining was performed, and the samples were examined using a ZEIS light microscope. Histological colitis damage scores were evaluated based on Dieleman\u0026rsquo;s scoring system, assessing inflammation severity, extent, and crypt damage. Inflammation was scored from 0 to 3, crypt damage from 0 to 4, with percentage involvement recorded.\u003c/p\u003e \u003cp\u003eThe data were analyzed using IBM SPSS V23. The normality of the data distribution was assessed using the Shapiro-Wilk test. For comparisons of normally distributed data across three or more groups, One-Way ANOVA was employed, with post-hoc analyses conducted using Tukey's test. For non-normally distributed data across three or more groups, the Kruskal-Wallis H test was used, followed by multiple comparisons with Dunn's test. Categorical data were compared using the Fisher-Freeman-Halton test. Results were presented as frequency (percentage) for categorical variables, and as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (minimum \u0026ndash; maximum) for quantitative variables. A significance level of p\u0026thinsp;\u0026lt;\u0026thinsp;0.050 was considered statistically significant\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eComparative analysis of the Disease Activity Index (DAI) showed significant differences in median weight scores across groups (p\u0026thinsp;=\u0026thinsp;0.003). The SF group had a median score of 0, while the Ethanol, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups had scores of 1, 1, 1, and 1.5, respectively. Stool consistency also differed significantly (p\u0026thinsp;=\u0026thinsp;0.005), with scores of 0 in the SF group, and 8, 4, 4, and 5 in the Ethanol, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups, respectively. Rectal bleeding showed significant differences (p\u0026thinsp;=\u0026thinsp;0.027), with the SF group scoring 0 and the Ethanol, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups scoring 7, 1, 3, and 3, respectively. Total DAI scores were significantly different (p\u0026thinsp;=\u0026thinsp;0.001), with medians of 0, 16.5, 10, 9, and 9.5 for the SF, Ethanol, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups, respectively.\u003c/p\u003e\n\u003cdiv\u003e\n \u003cdiv align=\"char\"\u003eTable 1. Dissease Activity Index Scores Across the Groups\u003c/div\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSaline\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEthanol-Colitis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTQ- Colitis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAPE- Colitis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAPE\u0026thinsp;+\u0026thinsp;TQ-Colitis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTest statistics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eWeight Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,5\u0026thinsp;\u0026plusmn;\u0026thinsp;0,76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;0,53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,5\u0026thinsp;\u0026plusmn;\u0026thinsp;1,69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,5\u0026thinsp;\u0026plusmn;\u0026thinsp;0,93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,1\u0026thinsp;\u0026plusmn;\u0026thinsp;1,08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e16,299\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;0)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;3)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;2)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;4)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,5 (0\u0026ndash;3)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eConsistency Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;1,51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,25\u0026thinsp;\u0026plusmn;\u0026thinsp;3,28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,25\u0026thinsp;\u0026plusmn;\u0026thinsp;5,23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,5\u0026thinsp;\u0026plusmn;\u0026thinsp;4,63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;2,39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;4,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e14,774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;4)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (6\u0026ndash;16)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (0\u0026ndash;14)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (0\u0026ndash;12)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (2\u0026ndash;8)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (0\u0026ndash;16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eBleeding Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,75\u0026thinsp;\u0026plusmn;\u0026thinsp;4,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,75\u0026thinsp;\u0026plusmn;\u0026thinsp;4,71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,5\u0026thinsp;\u0026plusmn;\u0026thinsp;5,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,75\u0026thinsp;\u0026plusmn;\u0026thinsp;5,23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,95\u0026thinsp;\u0026plusmn;\u0026thinsp;4,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e10,977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;0)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (0\u0026ndash;14)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0\u0026ndash;10)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (0\u0026ndash;14)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (0\u0026ndash;12)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (0\u0026ndash;14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDAI Total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;1,51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16,5\u0026thinsp;\u0026plusmn;\u0026thinsp;5,29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;8,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11,5\u0026thinsp;\u0026plusmn;\u0026thinsp;8,82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11,25\u0026thinsp;\u0026plusmn;\u0026thinsp;7,48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10,05\u0026thinsp;\u0026plusmn;\u0026thinsp;8,24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e19,169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;4)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16,5 (9\u0026ndash;23)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (0\u0026ndash;26)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (3\u0026ndash;30)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9,5 (3\u0026ndash;22\u003csup\u003e)a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,5 (0\u0026ndash;30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn colon tissue analysis, IL-10 levels varied significantly between groups (p=0.002), with the SF group showing a median of 141.14, while the Ethanol, TQ, CAPE, and CAPE+TQ groups had values of 137.79, 76.01, 80.32, and 78.17, respectively. Catalase (CAT) activity was significantly higher in the TQ, CAPE, and CAPE+TQ groups compared to the Ethanol group (p=0.001). GSH-Px levels also differed significantly between groups (p=0.003). Serum TNF-alpha levels showed significant variation (p=0.002), with higher levels in the SF group compared to CAPE and CAPE+TQ groups. Caspase-3, MDA, and CAT levels were significantly different between the SF, TQ, CAPE, and CAPE+TQ groups. NOS levels varied significantly (p=0.013), but no significant differences were found in multiple comparisons.\u0026nbsp;\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.5771%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 10.6041%;\"\u003e\n \u003cp\u003eTest statistics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIntraperitoneal administration of saline (SF) was applied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal ethanol was administered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal TQ was administered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal CAPE was administered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal CAPE+TQ were administered\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eTNF alfa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60,7 \u0026plusmn; 17,91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41,96 \u0026plusmn; 26,29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45,43 \u0026plusmn; 13,86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44,21 \u0026plusmn; 15,89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43,54 \u0026plusmn; 9,93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e47,17 \u0026plusmn; 18,09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e4,466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,347**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e55,75 (43,27 - 93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e50,57 (11,2 - 69,57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45,29 (26,69 - 67,86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e43,62 (14,7 - 64,92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42,73 (32,38 - 63,15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e46,6 (11,2 - 93)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eIL10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e143,67 \u0026plusmn; 43,77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e153,53 \u0026plusmn; 47,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e81,01 \u0026plusmn; 41,16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e88,21 \u0026plusmn; 36,51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e81,62 \u0026plusmn; 32,97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e109,61 \u0026plusmn; 50,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e17,405\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,002**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e141,14 (95,09 - 231,22)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e137,79 (106,52 - 259,2)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e76,01 (32,92 - 157,32)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80,32 (43,22 - 134,81)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78,17 (37,24 - 129,63)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e106,45 (32,92 - 259,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eCaspase3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,05 \u0026plusmn; 0,54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,09 \u0026plusmn; 0,72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,16 \u0026plusmn; 0,47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,87 \u0026plusmn; 0,36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,8 \u0026plusmn; 0,37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e1 \u0026plusmn; 0,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e3,407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,492**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e0,77 (0,6 - 2,16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,84 (0,44 - 2,75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,09 (0,78 - 2,21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,93 (0,12 - 1,39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,78 (0,07 - 1,31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e0,85 (0,07 - 2,75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eMDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16,37 \u0026plusmn; 0,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15,96 \u0026plusmn; 2,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14,55 \u0026plusmn; 4,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16,38 \u0026plusmn; 1,48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15,97 \u0026plusmn; 0,96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e15,85 \u0026plusmn; 2,28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e0,535\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,712*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e16,5 (15,48 - 17,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16,29 (12,98 - 18,31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15,61 (6,37 - 19,84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15,89 (14,92 - 18,79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15,69 (14,6 - 17,34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e15,93 (6,37 - 19,84)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eCAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e117,66 \u0026plusmn; 39,51\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e101 \u0026plusmn; 28,1\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e158,5 \u0026plusmn; 41,03\u003csup\u003eac\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e154,09 \u0026plusmn; 38,92\u003csup\u003eac\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e172,56 \u0026plusmn; 13,35\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e140,76 \u0026plusmn; 42,07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e6,318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,001*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e118,55 (58,6 - 197,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e106,85 (51,2 - 130,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e150,8 (115,7 - 224)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e147,85 (106,9 - 213,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e173,5 (152,3 - 193,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e128,85 (51,2 - 224)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eGSH-Px\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,36 \u0026plusmn; 0,01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,4 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,36 \u0026plusmn; 0,03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,43 \u0026plusmn; 0,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,41 \u0026plusmn; 0,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e0,39 \u0026plusmn; 0,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e16,161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,003**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e0,35 (0,34 - 0,39)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,39 (0,35 - 0,49)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,36 (0,29 - 0,4)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,43 (0,36 - 0,5)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,43 (0,35 - 0,47)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e0,38 (0,29 - 0,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eSOD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e105,14 \u0026plusmn; 15,32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e77,9 \u0026plusmn; 30,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e107,93 \u0026plusmn; 12,94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e110,08 \u0026plusmn; 37,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e97,96 \u0026plusmn; 7,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e99,8 \u0026plusmn; 25,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e8,007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,091**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e106,1 (84,8 - 129,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78,95 (28,2 - 122,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e113,15 (89,5 - 123)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e102,5 (78,8 - 200)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e95,9 (90,3 - 109,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e99,9 (28,2 - 200)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eXO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,02 \u0026plusmn; 0,03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 \u0026plusmn; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,01 \u0026plusmn; 0,03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,03 \u0026plusmn; 0,08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 \u0026plusmn; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e0,01 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e4,283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,369**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0 - 0,07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0 - 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0 - 0,07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0 - 0,22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0 - 0,01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e0 (0 - 0,22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e106,31 \u0026plusmn; 76,21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e70,47 \u0026plusmn; 50,12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e62,59 \u0026plusmn; 34,97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e109,25 \u0026plusmn; 42,92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e69,94 \u0026plusmn; 16,27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e83,71 \u0026plusmn; 49,96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e5,206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,267**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e91,75 (25 - 268)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e58,88 (10 - 167,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e56,63 (6,5 - 113,75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e100,63 (53,75 - 169,75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e62,38 (53 - 91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e76,5 (6,5 - 268)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eNOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,78 \u0026plusmn; 1,76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10,83 \u0026plusmn; 2,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,96 \u0026plusmn; 1,53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,78 \u0026plusmn; 1,48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10,61 \u0026plusmn; 1,64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e11,39 \u0026plusmn; 1,71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 6.7115%;\"\u003e\n \u003cp\u003e1,061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e0,390*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e12,32 (8,96 - 13,69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,33 (6,49 - 13,24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12,1 (9,56 - 13,99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,29 (9,79 - 13,76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10,26 (8,96 - 14,06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.5771%;\"\u003e\n \u003cp\u003e11,38 (6,49 - 14,06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e*One-Way ANOVA test; *\u003cem\u003eKruskal-Wallis H test; \u003csup\u003ea-c\u003c/sup\u003e: There is no significant difference between groups with the same letter; Mean \u0026plusmn; Standard Deviation; Median (Minimum \u0026ndash; Maximum)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eTable 2. Comparison of Quantitative Parameters in Tissue by Groups\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eTest statistics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIntraperitoneal administration of saline (SF) was applied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal ethanol was administered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal TQ was administered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal CAPE was administered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eColitis was induced, and intraperitoneal CAPE+TQ were administered\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eTNF alfa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e100,16 \u0026plusmn; 21,99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e71,18 \u0026plusmn; 18,15\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e79,07 \u0026plusmn; 27,19\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e61,51 \u0026plusmn; 14,57\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e53,37 \u0026plusmn; 24,28\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e73,06 \u0026plusmn; 26,23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e5,501\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,002*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e102,41 (54,84 - 129,86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e75,39 (36,36 - 88,71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e81,51 (41,53 - 127,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e59,77 (43,21 - 91,65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46,82 (32,51 - 96,01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e70,47 (32,51 - 129,86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eCaspase3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,14 \u0026plusmn; 0,17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,49 \u0026plusmn; 0,44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,55 \u0026plusmn; 0,64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,81 \u0026plusmn; 0,54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2,44 \u0026plusmn; 1,08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,69 \u0026plusmn; 0,75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e14,497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,006**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1,13 (0,86 - 1,38)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,31 (1,2 - 2,47)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,47 (1,02 - 3,02)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,69 (1,06 - 2,66)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2,27 (1,05 - 4,17)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1,45 (0,86 - 4,17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eMDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16,32 \u0026plusmn; 1,06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12,28 \u0026plusmn; 3,99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12,02 \u0026plusmn; 3,68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14,8 \u0026plusmn; 1,31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,47 \u0026plusmn; 4,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13,38 \u0026plusmn; 3,51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e15,349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,004**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e16,49 (14,52 - 17,82)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13,95 (5,65 - 15,57)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12,83 (6,53 - 17,42)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14,8 (12,58 - 16,78)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11,17 (3,15 - 16,21)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14,28 (3,15 - 17,82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eCAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2,76 \u0026plusmn; 2,11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2,76 \u0026plusmn; 1,64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4,4 \u0026plusmn; 2,71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10,06 \u0026plusmn; 9,73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13,9 \u0026plusmn; 3,33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6,78 \u0026plusmn; 6,48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e20,407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1,5 (1,5 - 7,3)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2,2 (1,5 - 5,9)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3,65 (1,5 - 8,8)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5,85 (1,5 - 26,4)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13,2 (10,2 - 19)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4,4 (1,5 - 26,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eGSH-Px\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,16 \u0026plusmn; 0,02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,17 \u0026plusmn; 0,02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,18 \u0026plusmn; 0,03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,16 \u0026plusmn; 0,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,14 \u0026plusmn; 0,06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,16 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e1,441\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0,241*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e0,16 (0,13 - 0,18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,17 (0,12 - 0,19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,18 (0,15 - 0,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,17 (0,08 - 0,24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,16 (0 - 0,19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,16 (0 - 0,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eSOD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60,95 \u0026plusmn; 10,63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e67,41 \u0026plusmn; 10,86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e121,21 \u0026plusmn; 157,28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e59,39 \u0026plusmn; 13,54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e60,85 \u0026plusmn; 6,54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e73,96 \u0026plusmn; 71,43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e3,894\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0,421**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e62,8 (43,3 - 75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e69,25 (50,4 - 78,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66,95 (53,2 - 509,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e64,55 (31,2 - 70,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e61,15 (50,2 - 68,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65,2 (31,2 - 509,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eXO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,09 \u0026plusmn; 0,03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,07 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,06 \u0026plusmn; 0,02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,07 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,06 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,07 \u0026plusmn; 0,04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e4,16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0,385**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e0,09 (0,02 - 0,14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,09 (0 - 0,11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,06 (0,04 - 0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,08 (0 - 0,11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,05 (0 - 0,12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0,08 (0 - 0,14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18,72 \u0026plusmn; 11,01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19,16 \u0026plusmn; 5,85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21,78 \u0026plusmn; 11,78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20,56 \u0026plusmn; 9,19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23,18 \u0026plusmn; 11,81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20,62 \u0026plusmn; 9,72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e1,337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0,855**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e17,38 (10,25 - 44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19,88 (11,75 - 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16,75 (11,75 - 44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20,75 (7,25 - 33,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18,5 (12,5 - 44,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18,5 (7,25 - 44,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eNOS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9,45 \u0026plusmn; 3,75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9,41 \u0026plusmn; 2,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9,49 \u0026plusmn; 1,99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16,3 \u0026plusmn; 6,45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17,77 \u0026plusmn; 8,31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12,35 \u0026plusmn; 6,06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e12,686\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,013**\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e7,65 (6,98 - 17,55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9,23 (7,16 - 14,06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9,81 (6,6 - 12,11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15,51 (7,54 - 27,64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20,66 (4,5 - 28,01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10,24 (4,5 - 28,01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e*One-Way ANOVA test; *\u003cem\u003eKruskal-Wallis H test\u003csup\u003e; a-b\u003c/sup\u003e: There is no significant difference between groups with the same letter; Mean \u0026plusmn; Standard Deviation; Median (Minimum \u0026ndash; Maximum)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Table 3. Comparison of Quantitative Parameters in Serum by Group \u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eHistopathological analysis revealed statistically significant relationships between the groups and various parameters of inflammation. In terms of inflammation severity, the control group had mostly no inflammation (62.5%), while the ETH, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups showed increasing levels of mild to severe inflammation, with a significant group effect (p\u0026thinsp;=\u0026thinsp;0.011). Regarding the spread of inflammation, the control group had no spread in 62.5% of the cases, whereas the ETH, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups exhibited mucosal to transmural involvement, with a statistically significant difference between the groups (p\u0026thinsp;=\u0026thinsp;0.016). Crypt damage also showed a significant group effect (p\u0026thinsp;=\u0026thinsp;0.025), with the control group displaying minimal damage and the experimental groups showing varying degrees of basal damage and crypt loss.\u003c/p\u003e\n\u003cp\u003eAdditionally, the percentage of colonic involvement was significantly related to the group (p\u0026thinsp;=\u0026thinsp;0.017), with higher levels of involvement observed in the ETH, TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups compared to the control. Despite these significant associations, post-hoc comparisons did not reveal any specific differences between the groups. There is a statistically significant difference in the median total scores among the groups (p\u0026thinsp;=\u0026thinsp;0.004). The median total score was 0 in the control group, 7.5 in the ETH group, 6.5 in the TQ group, 4 in the CAPE group, and 5 in the CAPE\u0026thinsp;+\u0026thinsp;TQ group. The control group showed significant differences compared to the ETH and TQ groups.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of Categorical Pathological Scores by Group\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eTest statistics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ep*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSaline\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eETH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTQ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAPE\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAPE\u0026thinsp;+\u0026thinsp;TQ\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInflammation Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (62,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e20,497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (62,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpread of Inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (62,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e19,824\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMucosa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (62,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSubmucosa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransmural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCyrpt Damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo Damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (62,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e21,78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,025\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasal 1/3 damaged\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBasal 2/3 damaged\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCyrpt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoss of crypt and surface ephitelium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePercentage Involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e%0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (62,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e22,767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e%1\u0026ndash;25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e%25\u0026ndash;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (37,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e%51\u0026ndash;75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e%76\u0026ndash;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (12,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eTest Statistics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ep*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.Deviation\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMedian (Min-Max)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSaline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,63\u0026thinsp;\u0026plusmn;\u0026thinsp;2,26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0\u0026ndash;5)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e15,606\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eETH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,88\u0026thinsp;\u0026plusmn;\u0026thinsp;3,44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,5 (4\u0026ndash;14)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;3,16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,5 (4\u0026ndash;14)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAPE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,25\u0026thinsp;\u0026plusmn;\u0026thinsp;2,31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (4\u0026ndash;9)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAPE\u0026thinsp;+\u0026thinsp;TQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,13\u0026thinsp;\u0026plusmn;\u0026thinsp;2,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (4\u0026ndash;11)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,58\u0026thinsp;\u0026plusmn;\u0026thinsp;3,46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,5 (0\u0026ndash;14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e*Kruskal-Wallis H test; **\u003csup\u003ea\u0026minus;b\u003c/sup\u003e: There is no significant difference between groups with the same letter.\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;5. Comparison of Total Scores by Group\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe Disease Activity Index (DAI) was used to evaluate colitis activity and symptoms, a scoring system first validated by Murthy et al. \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Daily DAI assessments were performed by an independent researcher, and the ethanol-colitis group had the highest median score (16.5), indicating the most severe colitis symptoms. The high DAI scores in the ethanol-colitis models compared to the SF group confirmed the appropriate induction of colitis. The DAI total scores in the TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups were significantly lower than those in the ethanol-colitis group, and the differences were statistically significant. Similar differences were observed across weight, consistency, and bleeding scores among the groups. The significant results of the disease activity index scores indicate that the colitis model induced in the subjects was successful.\u003c/p\u003e \u003cp\u003eTissue TNF-alpha levels were lowest in the CAPE\u0026thinsp;+\u0026thinsp;TQ group, while the ethanol-colitis group had the highest quantitative TNF-alpha levels, although the differences between groups were not statistically significant. In serum, the differences in TNF-alpha levels were statistically significant (p\u0026thinsp;=\u0026thinsp;0.002), with the lowest levels observed in the CAPE and CAPE\u0026thinsp;+\u0026thinsp;TQ groups, which were significantly lower than in the ethanol-colitis group. This suggests a potential synergistic anti-inflammatory effect when TQ and CAPE are used together. Currently, anti-TNF drugs are used in the treatment of ulcerative colitis, offering an alternative for steroid-resistant cases, while effectively preventing relapses and reducing colectomy rates. In this context, further clinical studies on the antioxidant properties of TQ and CAPE molecules could be beneficial for improving UC prognosis\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRegarding IL-10 levels in tissue, the ethanol-colitis group had a median of 137.79, compared to 76.01 in the TQ group, 80.32 in the CAPE group, and 78.17 in the CAPE\u0026thinsp;+\u0026thinsp;TQ group. The differences between the ethanol-colitis group and the TQ, CAPE, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups were statistically significant (p\u0026thinsp;=\u0026thinsp;0.002). The high IL-10 levels in colitis-induced rats align with findings in the literature, suggesting a response to high cytokine secretion. In our study, the elevated IL-10 levels observed in the colitis-induced subjects align with findings in the literature. A study by Fonseca et al. reported higher IL-10 producing cells in ulcerative colitis (UC) patients compared to healthy individuals. IL-10 was concentrated in macrophages and lymphocytes and spread across a wide area from the serosa to the mucosal layer. All biopsies showed increased IL-10-reactive cells in the colon serosa\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Melgar et al. also demonstrated increased IL-10 mRNA levels and IL-10 positive cells in UC patients' T-lymphocytes. These findings support that the elevated IL-10 levels in our study reflect an inflammatory response consistent with UC pathophysiology\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTissue catalase levels also showed significant differences (p\u0026thinsp;=\u0026thinsp;0.001), with the CAPE\u0026thinsp;+\u0026thinsp;TQ group having the highest levels, suggesting a synergistic effect in enhancing antioxidant activity. Serum catalase levels were significantly different as well (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with CAPE\u0026thinsp;+\u0026thinsp;TQ showing the highest levels, further supporting a positive synergistic effect. In a study by Rana et al., serum catalase levels were compared between UC patients in remission and those with active colitis, showing significantly higher catalase levels in the active colitis group\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Catalase plays a crucial role in eliminating hydrogen peroxide, and novel agents mimicking SOD and catalase are being explored as potential treatments for UC. Zhang et al. designed a nanosystem (Tpl/OxbCD NP) that effectively eliminates ROS components by mimicking SOD and catalase functions\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Based on this, catalase-mimicking molecules are gaining attention in UC treatment. Our study suggests that the potential anti-inflammatory effects of thymoquinone and CAPE may be linked to increased endogenous catalase levels. The difference in catalase levels between the SF group and the CAPE\u0026thinsp;+\u0026thinsp;TQ group suggests a synergistic effect of combined treatment on catalase activity.\u003c/p\u003e \u003cp\u003eFor GSH-Px, statistically significant differences were found in tissue levels (p\u0026thinsp;=\u0026thinsp;0.003), with higher levels in the CAPE and CAPE\u0026thinsp;+\u0026thinsp;TQ groups compared to the SF group. However, serum GSH-Px levels did not show significant differences. Tissue and serum SOD levels were not statistically significant across groups, although CAPE and TQ groups had higher quantitative levels. In a study by Okutan et al. on diabetic rat hearts, CAPE administration was examined for its effects on the oxidative/antioxidative balance. While GSH-Px activity did not differ between diabetic rats and controls, it was significantly higher in CAPE-treated subjects. This suggests, consistent with our study, that CAPE may positively influence GSH-Px activity, independent of the underlying pathological condition\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSerum caspase-3 levels showed statistically significant differences (p\u0026thinsp;=\u0026thinsp;0.006), with the highest levels in the CAPE\u0026thinsp;+\u0026thinsp;TQ group, suggesting a possible involvement in the anti-inflammatory mechanisms of these agents. A study by Qi TY et al. demonstrated that apoptosis induced by visilizumab increases apoptosis in activated T-lymphocytes, reducing inflammation in the colonic lamina propria and facilitating rapid remission in ulcerative colitis \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Similarly, Shteingart et al. showed that inhibiting the caspase-3 mechanism leads to defective T-lymphocyte responses, triggering inflammation. In our study, the observed increase in serum caspase-3 levels in the CAPE, TQ, and CAPE\u0026thinsp;+\u0026thinsp;TQ groups raises the question of whether these agents may operate through novel anti-inflammatory mechanisms, which warrant further investigation at the cellular level\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. New studies are needed to elucidate the precise mechanisms behind their anti-inflammatory effects.\u003c/p\u003e \u003cp\u003eSerum MDA levels were significantly different (p\u0026thinsp;=\u0026thinsp;0.004), with lower levels in the TQ and CAPE\u0026thinsp;+\u0026thinsp;TQ groups compared to the ethanol-colitis group, indicating a protective effect of these molecules against oxidative damage. In a study by Kruidenier et al., investigating the relationship between oxidative damage and inflammatory bowel disease (IBD) at the cellular level, MDA levels were found to be significantly higher in the active inflammation group of ulcerative colitis (UC) patients compared to those without inflammation and the control group\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. This finding aligns with our study, where the lowest serum MDA levels were observed in the CAPE\u0026thinsp;+\u0026thinsp;TQ group, suggesting that these two agents may have protective effects against oxidative damage to cell membranes.\u003c/p\u003e \u003cp\u003eThere were no significant differences in XO levels between groups, consistent with previous studies suggesting XO may not be the primary source of superoxide production in colitis\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSerum NOS levels showed a significant difference (p\u0026thinsp;=\u0026thinsp;0.013), with higher levels in the CAPE\u0026thinsp;+\u0026thinsp;TQ group, which, combined with lower clinical and histopathological inflammation scores, suggests a protective role of NOS in colon structure. However, more detailed studies are needed to fully understand the mechanisms. A study on ulcerative colitis patients found that nitric oxide (NO) levels were significantly higher in the rectal dialysate of patients with active colitis\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. However, the use of NOS inhibitors in experimental colitis models has yielded inconsistent results. Non-specific NOS inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), reduced intestinal inflammation in some models, but in others, they either provided no protection or worsened inflammation\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. In a study by McCafferty et al., rats genetically unable to produce NOS were compared with normal rats after acetic acid-induced colitis, showing more severe inflammation in the NOS-deficient group\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. In our study, CAPE\u0026thinsp;+\u0026thinsp;TQ-treated subjects exhibited higher NOS levels and lower clinical and histopathological inflammation scores, suggesting a protective role of NOS and NO in maintaining colon cell structure. However, further research is needed to explore the underlying cellular mechanisms in detail.\u003c/p\u003e \u003cp\u003eHistopathological analysis revealed statistically significant differences in total inflammation scores among the groups (p\u0026thinsp;=\u0026thinsp;0.004). The median score in the SF group was 0, while it was 7.5 in the ethanol-colitis group, 6.5 in the TQ group, 4 in the CAPE group, and 5 in the CAPE\u0026thinsp;+\u0026thinsp;TQ group. There was a significant difference between the SF group and the ethanol-colitis and TQ groups. CAPE and CAPE\u0026thinsp;+\u0026thinsp;TQ showed no significant difference from the SF group, suggesting that the combination of CAPE and TQ may have stronger anti-inflammatory effects than TQ alone. In a study by Mahgoub, rats pre-treated with 10 mg/kg oral thymoquinone (TQ) for three days prior to acetic acid-induced colitis showed lower levels of inflammation in colon specimens compared to the colitis-only group\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. This suggests that, in addition to its anti-inflammatory effect, TQ may offer protective benefits in colitis. Similarly, in our study, CAPE administered intraperitoneally after the onset of acute colitis was found to be more effective in reducing inflammation, as observed in histopathological examinations. Tambuwala et al. also demonstrated that CAPE reduced fibrosis at the cellular level in a DSS-induced chronic colon inflammation model\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Our results further confirm the anti-inflammatory efficacy of CAPE in acute colitis.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThe hypothesis of our study is that CAPE and thymoquinone (TQ) would effectively reduce inflammation in an acetic acid-induced colitis model. Our findings largely support this hypothesis, with histopathological analysis indicating that CAPE demonstrates slightly stronger anti-inflammatory effects than TQ. Notably, the combination of CAPE and TQ showed synergistic potential, as evidenced by enhanced biochemical parameters, including oxidative stress markers and antioxidant levels. This synergistic effect suggests that the co-administration of CAPE and TQ may offer additional benefits in suppressing inflammatory processes. Our study is the first to compare and combine these two molecules in a colitis model, providing valuable insights for future therapeutic approaches. The results indicate that combining CAPE and TQ could be a more effective anti-inflammatory strategy for treating colitis, highlighting its potential for future clinical evaluation. These findings introduce a novel perspective on anti-inflammatory agents in experimental colitis models and suggest that the CAPE-TQ combination warrants further exploration in clinical settings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding or assistance for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Consideratons\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study was approved by the Local Ethics Committee of Ankara training and Research Hospital and Ministy of Health(meeting number: 0076, with decision number: 736, on August 10, 2023.). All experimental procedures were conducted in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes, ensuring the highest standards of animal welfare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDarakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. \u003cem\u003ePharmacol Res\u003c/em\u003e. May-Jun 2015;95-96:138-58. doi:10.1016/j.phrs.2015.03.011\u003c/li\u003e\n\u003cli\u003eMurtaza G, Karim S, Akram MR, et al. Caffeic acid phenethyl ester and therapeutic potentials. \u003cem\u003eBiomed Res Int\u003c/em\u003e. 2014;2014:145342. doi:10.1155/2014/145342\u003c/li\u003e\n\u003cli\u003eMurthy S, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. \u003cem\u003eDigestive diseases and sciences\u003c/em\u003e. 1993;38:1722-1734. \u003c/li\u003e\n\u003cli\u003eKornbluth A, Sachar DB, Gastroenterology PPCotACo. Ulcerative colitis practice guidelines in adults: American college of gastroenterology, practice parameters committee. \u003cem\u003eOfficial journal of the American College of Gastroenterology| ACG\u003c/em\u003e. 2010;105(3):501-523. \u003c/li\u003e\n\u003cli\u003eD\u0026apos;haens GR, Panaccione R, Higgins PD, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn\u0026apos;s and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? \u003cem\u003eOfficial journal of the American College of Gastroenterology| ACG\u003c/em\u003e. 2011;106(2):199-212. \u003c/li\u003e\n\u003cli\u003eFonseca-Camarillo G, Furuzawa-Carballeda J, Llorente L, Yamamoto-Furusho JK. IL-10\u0026mdash;and IL-20\u0026mdash;expressing epithelial and inflammatory cells are increased in patients with ulcerative colitis. \u003cem\u003eJournal of clinical immunology\u003c/em\u003e. 2013;33:640-648. \u003c/li\u003e\n\u003cli\u003eMelgar S, Yeung MM, Bas A, et al. Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis. \u003cem\u003eClinical \u0026amp; Experimental Immunology\u003c/em\u003e. 2003;134(1):127-137. \u003c/li\u003e\n\u003cli\u003eRana SV, Sharma S, Prasad KK, Sinha SK, Singh K. Role of oxidative stress \u0026amp; antioxidant defence in ulcerative colitis patients from north India. \u003cem\u003eIndian Journal of Medical Research\u003c/em\u003e. 2014;139(4):568-571. \u003c/li\u003e\n\u003cli\u003eShen X, Shi R, Zhang H, Li K, Zhao Y, Zhang R. The Toll-like receptor 4 D299G and T399I polymorphisms are associated with Crohn\u0026rsquo;s disease and ulcerative colitis: a meta-analysis. 2010. p. 69-77.\u003c/li\u003e\n\u003cli\u003eOkutan H, Ozcelik N, Yilmaz HR, Uz E. Effects of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. \u003cem\u003eClinical Biochemistry\u003c/em\u003e. 2005;38(2):191-196. \u003c/li\u003e\n\u003cli\u003eQi TY, Saruta M, Papadakis KA. Visilizumab induces apoptosis of mucosal T lymphocytes in ulcerative colitis through activation of caspase 3 and 8 dependent pathways. \u003cem\u003eClinical Immunology\u003c/em\u003e. 2008;127(3):322-329. \u003c/li\u003e\n\u003cli\u003eShteingart S, Rapoport M, Grodzovski I, et al. Therapeutic potency of IL2\u0026ndash;caspase 3 targeted treatment in a murine experimental model of inflammatory bowel disease. \u003cem\u003eGut\u003c/em\u003e. 2009;58(6):790-798. \u003c/li\u003e\n\u003cli\u003eKruidenier L, Kuiper I, Lamers CB, Verspaget HW. Intestinal oxidative damage in inflammatory bowel disease: semi‐quantification, localization, and association with mucosal antioxidants. \u003cem\u003eThe Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland\u003c/em\u003e. 2003;201(1):28-36. \u003c/li\u003e\n\u003cli\u003eReynolds P, Rhenius S, Hunter J. Xanthine oxidase activity is not increased in the colonic mucosa of ulcerative colitis. \u003cem\u003eAlimentary pharmacology \u0026amp; therapeutics\u003c/em\u003e. 1996;10(5):737-741. \u003c/li\u003e\n\u003cli\u003eRoediger W, Lawson M, Nance S, Radcliffe B. Detectable colonic nitrite levels in inflammatory bowel disease\u0026ndash;mucosal or bacterial malfunction? \u003cem\u003eDigestion\u003c/em\u003e. 1986;35(4):199-204. \u003c/li\u003e\n\u003cli\u003eBoughton-Smith N, Evans S, Whittle B, et al. Nitric oxide synthase activity in ulcerative colitis and Crohn\u0026apos;s disease. \u003cem\u003eThe Lancet\u003c/em\u003e. 1993;342(8867):338-e2. \u003c/li\u003e\n\u003cli\u003eGrisham MB, Specian RD, Zimmerman TE. Effects of nitric oxide synthase inhibition on the pathophysiology observed in a model of chronic granulomatous colitis. \u003cem\u003eJournal of Pharmacology and Experimental Therapeutics\u003c/em\u003e. 1994;271(2):1114-1121. \u003c/li\u003e\n\u003cli\u003eMcCafferty DM, Mudgett JS, Swain MG, Kubes P. Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. \u003cem\u003eGastroenterology\u003c/em\u003e. 1997;112(3):1022-1027. \u003c/li\u003e\n\u003cli\u003eMahgoub AA. Thymoquinone protects against experimental colitis in rats. \u003cem\u003eToxicology letters\u003c/em\u003e. 2003;143(2):133-143. \u003c/li\u003e\n\u003cli\u003eTambuwala MM, Kesharwani P, Shukla R, Thompson PD, McCarron PA. Caffeic acid phenethyl ester (CAPE) reverses fibrosis caused by chronic colon inflammation in murine model of colitis. \u003cem\u003ePathology-Research and Practice\u003c/em\u003e. 2018;214(11):1909-1911. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ulcerative Colitis, Thymoquinone, Caffeic Acid Phenetyl Ester, Experimental","lastPublishedDoi":"10.21203/rs.3.rs-5815391/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5815391/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eThis study aims to model ulcerative colitis in rats using acetic acid and monitor colitis development with the \"Disease Activity Index (DAI).\" Additionally, the clinical, biochemical, and histopathological effects of thymoquinone (TQ) and caffeic acid phenethyl ester (CAPE) on this model are examined.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eThe study used 40 male Wistar Albino rats, weighing between 190\u0026ndash;303 grams. The rats were divided into five groups of 8 each: Group 1 (Control) received intraperitoneal 0.9% saline solution for 5 days; Group 2 (Colitis) received acetic acid to induce colitis and 10% ethanol solution intraperitoneally for 5 days; Group 3 (TQ) received acetic acid to induce colitis and intraperitoneal thymoquinone (10 mg/kg/day) for 5 days; Group 4 (CAPE) received acetic acid to induce colitis and intraperitoneal caffeic acid (10 micromol/kg/day) for 5 days; Group 5 (TQ\u0026thinsp;+\u0026thinsp;CAPE) received acetic acid to induce colitis and intraperitoneal thymoquinone and caffeic acid for 5 days. On the 5th day, rats underwent laparotomy under anesthesia, colectomy was performed, and colon samples were taken for biochemical and histological analysis. Serum samples were also collected for biochemical analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSignificant differences were observed in the Disease Activity Index, TNF-α, catalase, glutathione peroxidase, IL-10, and MDA, indicating a balance between oxidant and antioxidant parameters. CAPE was found to have a higher anti-inflammatory effect than TQ histopathologically. The combined application of CAPE and TQ showed a synergistic effect, reducing oxidative stress markers and enhancing antioxidant levels.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe hypothesis of this study is that CAPE and TQ will effectively reduce inflammation in an experimental colitis model induced by acetic acid. The results largely support this hypothesis, showing that CAPE has a higher anti-inflammatory efficacy than TQ and that their combined use is more effective in reducing inflammation. These findings suggest that CAPE and TQ could be a potential combination for colitis treatment and should be considered for clinical applications. This study provides new insights into the use of anti-inflammatory agents in experimental colitis models and highlights the potential advantages of combining CAPE and TQ in clinical settings.\u003c/p\u003e","manuscriptTitle":"Synergistic Potential of Thymoquinone and Caffeic Acid in Experimental Ulcerative Colitis: A Biochemical and Histopathological Investigation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-17 07:43:49","doi":"10.21203/rs.3.rs-5815391/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"32d1aaf4-1228-48b9-a9e3-6bef3d101e3e","owner":[],"postedDate":"January 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-21T20:08:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-17 07:43:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5815391","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5815391","identity":"rs-5815391","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}