ORİGANUM ONİTES L. ETANOLİK EKSTRAKTI OKSİDAN, İNFLAMATUAR VE APOPTOTİK BELİRTEÇLERİ DÜZENLEYEREK SIÇANLARDA ASETİK ASİT İLE İNDÜKLENEN ÜLSERATİF KOLİTİ HAFİFLETİR

Yıl 2025, Cilt: 49 Sayı: 3, 631 - 650, 19.09.2025

Dilek Özbeyli , Ali Şen , Leyla Bitiş , Naziye Özkan Yenal , Ayşe Nur Hazar Yavuz , Deniz Mukaddes Türet , Meral Yüksel , Ahmet Doğan , Aslı Aykaç

https://doi.org/10.33483/jfpau.1582539

Öz

Amaç: Bu çalışmada Origanum onites etanolik özütünün (O. onites EE) antioksidan ve anti-inflamatuar etkileri in vitro olarak ve inflamasyon, apoptoz, oksidatif stres ve doku hasarıyla ilişkili parametreler üzerindeki etkileri asetik asit (AA) ile indüklenen sıçan ülseratif kolit (UC) modelinde değerlendirilmiştir.
Gereç ve Yöntem: O. onites'in kurutulmuş kısımları maserasyon yöntemi kullanılarak etanol ile ekstre edildi. Daha sonra, ekstrenin anti-DPPH ve anti-ABTS serbest radikal temizleme, anti-5-lipoksijenaz aktiviteleri ve toplam sekonder metabolik miktarları ölçüldü. Sıçan grupları kontrol + salin (C), UC + salin (A), UC + O. onites EE (O), UC + Sülfasalazin (S) olarak belirlendi. Tüm tedaviler 3 ardışık gün boyunca günde bir kez uygulandı.
Sonuç ve Tartışma: O. onites EE, toplam fenolik, flavonoid ve triterpen içeriklerine iyi miktarda, sahipti ve ABTS, DPPH radikallerine karşı yüksek bir antioksidan aktivite ve 5-LOX enzimine karşı yüksek bir anti-inflamatuar aktivite gösterdi. AA ile uygulanması ile artan luminol-lusigenin, TNF-α, IL-1, IL-17, TLR-9, kaspaz-3, kaspaz-9, MMP-3, makroskobik ve mikroskobik skorlar, O. onites EE ve sülfasalazin tedavileriyle azaldı. Sonuç olarak, O. onites EE'nin sıçanlarda kolit üzerinde iyi bir terapötik etkisi vardır; bu da esas olarak total flavonoid, fenolik ve triterpen içeriği ve Anti-5-LOX ve serbest radikal temizleyici aktivitesinden kaynaklanmaktadır.

Anahtar Kelimeler

Anti-5-LOX , apoptoz , IL-17 , IL-10 , Origanum onites , TRL-9 , ülseratif kolit

Proje Numarası

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ORIGANUM ONITES L. ETHANOLIC EXTRACT ALLEVIATES ACETIC ACID-INDUCED ULCERATIVE COLITIS IN RATS BY REGULATING OXIDANT, INFLAMMATORY, AND APOPTOTIC MARKERS

Öz

Objective: This study aims to evaluate the antioxidant and anti-inflammatory effects of Origanum onites ethanolic extract (O. onites EE) in vitro and its effects on inflammation, apoptosis, oxidative stress, and tissue damage-related parameters in the acetic acid (AA)-induced ulcerative colitis (UC) model in rats.
Material and Method: Dried parts of O. onites were extracted with ethanol using the maceration method. Then, the extract’s anti-DPPH and anti-ABTS free radical scavenging, anti-5-lipoxygenase (LOX) activities, and total secondary metabolic quantities were evaluated in vitro. The rat groups were determined as control + saline (C), AA + saline (A), AA + O. onites EE (O), AA + Sulfasalazine (S). The treatments were applied once a day for 3 consecutive days.
Result and Discussion: O. onites EE showed high amount of total phenolic, total flavonoid, and total triterpene contents, high antioxidant activity against ABTS, DPPH radicals, and anti-inflammatory effects against 5-LOX enzyme. Due to AA-induction, increased luminol-lucigenin, TNF-α, IL-1β, IL-17, TLR-9, caspase-3, caspase-9, MMP-3, macroscopic and microscopic scores attenuated by O. onites EE and sulfasalazine treatments. In conclusion, O. onites EE has a significant therapeutic effect on rats' colitis due to its total flavonoid, phenolic, and triterpene content, and its Anti-5-LOX and free radical scavenging activity.

Anahtar Kelimeler

Anti-5-LOX , apoptosis , IL-17 , IL-10 , Origanum onites , TLR-9 , ulcerative colitis

Etik Beyan

All procedures for experimental protocols of the present study involving animals were performed following the ethical standards of the institution or practice at which the studies were conducted. Approval was granted by the Ethics Committee of University Marmara (Date: 2023, No:50.2023mar). All experimental practices concerning rats were executed following "The Guide for the Care and Use of Laboratory Animals" (www.nap.edu/ catalog/5140.html) and the principles of ARRIVE guidelines.

Destekleyen Kurum

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Proje Numarası

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Teşekkür

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Kaynakça

• 1. da Silva, B.C., Lyra, A.C., Rocha, R., Santana, G.O. (2014). Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis. World Journal of Gastroenterology, 20(28), 9458-9467. [CrossRef]
• 2. Calvet, X., Argüelles-Arias, F., López-Sanromán, A., Cea-Calvo, L., Juliá, B., de Santos, C.R., Carpio, D. (2018). Patients' perceptions of the impact of ulcerative colitis on social and professional life: Results from the UC-LIFE survey of outpatient clinics in Spain. Patient Preference and Adherence, 12, 1815-1823. [CrossRef]
• 3. Jairath, V., Feagan, B.G. (2020). Global burden of inflammatory bowel disease. The Lancet. Gastroenterology & Hepatology, 5(1), 2-3. [CrossRef]
• 4. Matsuoka, K., Kobayashi, T., Ueno, F., Matsui, T., Hirai, F., Inoue, N., Kato, J., Kobayashi, K., Kobayashi, K., Koganei, K., Kunisaki, R., Motoya, S., Nagahori, M., Nakase, H., Omata, F., Saruta, M., Watanabe, T., Tanaka, T., Kanai, T., Noguchi, Y., Takahashi, K.I., Watanabe, K., Hibi, T., Suzuki, Y., Watanabe, M., Sugano, K., Shimosegawa, T. (2018). Evidence-based clinical practice guidelines for inflammatory bowel disease. Journal of Gastroenterology, 53, 305-353. [CrossRef]
• 5. Sies H. (2015). Oxidative stress: A concept in redox biology and medicine. Redox biology, 4, 180-183. [CrossRef]
• 6. Phaniendra, A., Jestadi, D.B., Periyasamy, L. (2015). Free radicals: Properties, sources, targets, and their implication in various diseases. Indian Journal of Clinical Biochemistry: IJCB, 30(1), 11-26. [CrossRef]
• 7. Hussain, T., Tan, B., Yin, Y., Blachier, F., Tossou, M.C., Rahu, N. (2016). Oxidative stress and Inflammation: What polyphenols can do for us? Oxidative Medicine and Cellular Longevity, 7432797. [CrossRef]
• 8. Adams, S.M., Close, E.D., Shreenath, A.P. (2022). Ulcerative colitis: Rapid evidence review. American family physician, 105(4), 406-411.
• 9. Ungaro, R., Mehandru, S., Allen, P.B., Peyrin-Biroulet, L., Colombel, J.F. (2017). Ulcerative colitis. Lancet (London, England), 389(10080), 1756-1770. [CrossRef]
• 10. Mittal, M., Siddiqui, M.R., Tran, K., Reddy, S.P., Malik, A.B. (2014). Reactive oxygen species in inflammation and tissue injury. Antioxidants & Redox Signaling, 20(7), 1126-1167. [CrossRef]
• 11. Suluvoy, J.K., Sakthivel, K.M., Guruvayoorappan, C., Berlin Grace, V.M. (2017). Protective effect of Averrhoa bilimbi L. fruit extract on ulcerative colitis in wistar rats via regulation of inflammatory mediators and cytokines. Biomedicine & Pharmacotherapy, 91, 1113-1121. [CrossRef]
• 12. Iyer, S.S., Cheng, G. (2012). Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Critical Reviews in Immunology, 32(1), 23-63. [CrossRef]
• 13. Zenobia, C., Hajishengallis, G. (2015). Basic biology and role of interleukin-17 in immunity and inflammation. Periodontology 2000, 69(1), 142-159. [CrossRef]
• 14. Pudla, M., Saengfak, R., Luangjindarat, C., Utaisincharoen, P. (2023). Pyroptosis induced by TLR9 ligand, ODN1826, requires ROS production and caspase-11 activation in Raw264.7 cells. Asian Pacific journal of Allergy and Immunology. [CrossRef]
• 15. Andoh, A., Yagi, Y., Shioya, M., Nishida, A., Tsujikawa, T., Fujiyama, Y. (2008). Mucosal cytokine network in inflammatory bowel disease. World journal of gastroenterology, 14(33), 5154-5161. [CrossRef]
• 16. Garlanda, C., Dinarello, C.A., Mantovani, A. (2013). The interleukin-1 family: Back to the future. Immunity, 39(6), 1003-1018. [CrossRef]
• 17. Marônek, M., Marafini, I., Gardlík, R., Link, R., Troncone, E., Monteleone, G. (2021). Metalloproteinases in inflammatory bowel diseases. Journal of Inflammation Research, 14, 1029-1041. [CrossRef]
• 18. Kordjazy, N., Haj-Mirzaian, A., Haj-Mirzaian, A., Rohani, M.M., Gelfand, E.W., Rezaei, N., Abdolghaffari, A.H. (2018). Role of toll-like receptors in inflammatory bowel disease. Pharmacological Research, 129, 204-215. [CrossRef]
• 19. Gajendran, M., Loganathan, P., Jimenez, G., Catinella, A.P., Ng, N., Umapathy, C., Ziade, N., Hashash, J.G. (2019). A comprehensive review and update on ulcerative colitis. Disease-a-Month, 65(12), 100851. [CrossRef]
• 20. Atanasov, A.G., Waltenberger, B., Pferschy-Wenzig, E.M., Linder, T., Wawrosch, C., Uhrin, P., Temml, V., Wang, L., Schwaiger, S., Heiss, E.H., Rollinger, J.M., Schuster, D., Breuss, J.M., Bochkov, V., Mihovilovic, M.D., Kopp, B., Bauer, R., Dirsch, V.M., Stuppner, H. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33(8), 1582-1614. [CrossRef]
• 21. Costa, C.A.R.A., Quaglio, A.E.V., Di Stasi, L.C. (2018). Pfaffia paniculata (Brazilian ginseng) extract modulates Mapk and mucin pathways in intestinal inflammation. Journal of Ethnopharmacology, 213, 21-25. [CrossRef]
• 22. Arunachalam, K., Damazo, A.S., Macho, A., Lima, J.C.D.S., Pavan, E., Figueiredo, F.F., Oliveira, D.M., Cechinel-Filho, V., Wagner, T.M., Martins, D.T.O. (2020). Piper umbellatum L. (Piperaceae): Phytochemical profiles of the hydroethanolic leaf extract and intestinal anti-inflammatory mechanisms on 2,4,6 trinitrobenzene sulfonic acid induced ulcerative colitis in rats. Journal of Ethnopharmacology, 254, 112707. [CrossRef]
• 23. Ullah, A., Munir, S., Badshah, S.L., Khan, N., Ghani, L., Poulson, B.G., Emwas, A.H., Jaremko, M. (2020). Important flavonoids and their role as a therapeutic agent. Molecules (Basel, Switzerland), 25(22), 5243. [CrossRef]
• 24. Tepe, B., Cakir, A., Sihoglu Tepe, A. (2016). Medicinal uses, phytochemistry, and pharmacology of Origanum onites (L.): A review. Chemistry & Biodiversity, 13(5), 504-520. [CrossRef]
• 25. Canli, K., Bozyel, M.E., Turu, D., Benek, A., Simsek, O., Altuner, E.M. (2023). Biochemical, antioxidant properties and antimicrobial activity of steno-endemic Origanum onites. Microorganisms, 11(8), 1987. [CrossRef]
• 26. Lukas, B., Novak, J. (2020). Origanum vulgare L. and Origanum onites L. (Oregano). In: Novak, J., Blüthner, WD. (eds) Medicinal, Aromatic and Stimulant Plants. Handbook of Plant Breeding, vol. 12. Springer, Cham. [CrossRef]
• 27. Dundar, E., Olgun, E.G., Isiksoy, S., Kurkcuoglu, M., Baser, K.H., Bal, C. (2008). The effects of intra-rectal and intra-peritoneal application of Origanum onites L. essential oil on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in the rat. Experimental and Toxicologic Pathology, 59(6), 399-408. [CrossRef]
• 28. Aykac, A., Teralı, K., Özbeyli, D., Ede, S., Albayrak, Ö., Başer, K.H.C., Şener, G. (2022). A multi-parameter evaluation of the neuroprotective and cognitive-enhancing effects of Origanum onites L. (Turkish Oregano) essential oil on scopolamine-induced amnestic rats. Metabolic Brain Disease, 37(4), 1041-1055. [CrossRef]
• 29. Boal Carvalho, P., Cotter, J. (2017). Mucosal healing in ulcerative colitis: A comprehensive Review. Drugs, 77(2), 159-173. [CrossRef]
• 30. Nenci, A., Becker, C., Wullaert, A., Gareus, R., van Loo, G., Danese, S., Huth, M., Nikolaev, A., Neufert, C., Madison, B., Gumucio, D., Neurath, M.F., Pasparakis, M. (2007). Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature, 446(7135), 557-561. [CrossRef]
• 31. McKenzie, S.J., Baker, M.S., Buffinton, G.D., Doe, W.F. (1996). Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. The Journal of Clinical Investigation, 98(1), 136-141. [CrossRef]
• 32. von Lampe, B., Barthel, B., Coupland, S.E., Riecken, E.O., Rosewicz, S. (2000). Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut, 47(1), 63-73. [CrossRef]
• 33. Yang, C., Wang, W., Li, S., Qiao, Z., Ma, X., Yang, M., Zhang, J., Cao, L., Yao, S., Yang, Z., Wang, W. (2023). Identification of cuproptosis hub genes contributing to the immune microenvironment in ulcerative colitis using bioinformatic analysis and experimental verification. Frontiers in Immunology, 14, 1113385. [CrossRef]
• 34. Şen, A., Özbeyli, D., Teralı, K., Göger, F., Yıldırım, A., Ertaş, B., Doğan, A., Bitiş, L., Şener, G. (2023). Protective effects of Rubus tereticaulis leaves ethanol extract on rats with ulcerative colitis and bio-guided isolation of its active compounds: A combined in silico, in vitro and in vivo study. Chemico-Biological Interactions, 369, 110263. [CrossRef]
• 35. Zou, Y., Chang, S.K., Gu, Y., Qian, S.Y. (2011). Antioxidant activity and phenolic compositions of lentil (Lens culinaris var. Morton) extract and its fractions. Journal of Agricultural and Food Chemistry, 59(6), 2268-2276. [CrossRef]
• 36. Phosrithong, N., Nuchtavorn, N. (2016). Antioxidant and anti-inflammatory activites of Clerodendrum leaf extracts collected in Thailand. European Journal of Integrative Medicine, 8(3), 281-285. [CrossRef]
• 37. Zhang, R., Zeng, Q., Deng, Y., Zhang, M., Wei, Z., Zhang, Y., Tang, X. (2013). Phenolic profiles and antioxidant activity of litchi pulp of different cultivars cultivated in Southern China. Food Chemistry, 136(3-4), 1169-1176. [CrossRef]
• 38. Gao, X., Ohlander, M., Jeppsson, N., Björk, L., Trajkovski, V. (2000). Changes in antioxidant effects and their relationship to phytonutrients in fruits of sea buckthorn (Hippophae rhamnoides L.) during maturation. Journal of Agricultural and Food Chemistry, 48(5), 1485-1490. [CrossRef]
• 39. Yıldırım, A., Şen, A., Doğan, A., Bitis, L. (2019). Antioxidant and anti-inflammatory activity of capitula, leaf and stem extracts of Tanacetum cilicicum (Boiss.) Grierson. International Journal of Secondary Metabolite, 6(2), 211-222. [CrossRef]
• 40. Chang, C.L., Lin, C.S., Lai, G.H. (2012). Phytochemical characteristics, free radical scavenging activities, and neuroprotection of five medicinal plant extracts. Evidence-based Complementary and Alternative Medicine: eCAM, 984295. [CrossRef]
• 41. MacPherson, B.R., Pfeiffer C.J. (1978). Experimental production of diffuse colitis in rats. Digestion, 17(2), 135–150. [CrossRef]
• 42. Ansari, M.N., Rehman, N.U., Karim, A., Soliman, G.A., Ganaie, M.A., Raish, M., Hamad, A.M. (2021). Role of oxidative stress and inflammatory cytokines (TNF-α and IL-6) in acetic acid-induced ulcerative colitis in rats: Ameliorated by otostegia fruticosa. Life (Basel, Switzerland), 11(3), 195. [CrossRef]
• 43. El-Meligy, R.M., Awaad, A.S., Soliman, G.A., Bacha, A.B., Alafeefy, A.M., Kenawy, S.A. (2015). Prophylactic and curative anti-ulcerative colitis activity and the possible mechanisms of action of some desert plants. Journal of Enzyme Inhibition and Medicinal Chemistry, 30(2), 250-258. [CrossRef]
• 44. Karakoyun, B., Ertaş, B., Yüksel, M., Akakın, D., Çevik, Ö., Şener, G. (2018). Ameliorative effects of riboflavin on acetic acid-induced colonic injury in rats. Clinical and Experimental Pharmacology & Physiology, 45(6), 563-572. [CrossRef]
• 45. Iseri, S.O., Ersoy, Y., Ercan, F., Yuksel, M., Atukeren, P., Gumustas, K., Alican, I. (2009). The effect of sildenafil, a phosphodiesterase-5 inhibitor, on acetic acid-induced colonic inflammation in the rat. Journal of Gastroenterology and Hepatology, 24(6), 1142-1148. [CrossRef]
• 46. Haklar, G., Ulukaya-Durakbaşa, C., Yüksel, M., Dağli, T., Yalçin, A.S. (1998). Oxygen radicals and nitric oxide in rat mesenteric ischaemia-reperfusion: Modulation by L-arginine and NG-nitro-L-arginine methyl ester. Clinical Experimental Pharmacology and Physiology, 25(11), 908-912. [CrossRef]
• 47. Arabacı Tamer, S., Akbulut, S., Erdoğan, Ö., Çevik, Ö., Ercan, F., Yeğen, B.Ç. (2023). Neuropeptide W exhibits preventive and therapeutic effects on acetic acid-induced colitis via modulation of the cyclooxygenase enzyme system. Digestive Diseases and Sciences, 68(6), 2441-2453. [CrossRef]
• 48. Indarti, K., Apriani, E.F., Wibowo, A.E., Simanjuntak, P. (2019). Antioxidant activity of ethanolic extract and various fractions from green tea (Camellia sinensis L.) leaves. Pharmacognosy Journal, 11(4), 771-776. [CrossRef]
• 49. Randhawa, P.K., Singh, K., Singh, N., Jaggi, A.S. (2014). A review on chemical-induced inflammatory bowel disease models in rodents. The Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology, 18(4), 279-288. [CrossRef]
• 50. Cook, M.D., Martin, S.A., Williams, C., Whitlock, K., Wallig, M.A., Pence, B.D., Woods, J.A. (2013). Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis. Brain, Behavior, and Immunity, 33, 46-56. [CrossRef]
• 51. Chen, K., Shang, S., Yu, S., Cui, L., Li, S., He, N. (2022). Identification and exploration of pharmacological pyroptosis-related biomarkers of ulcerative colitis. Frontiers in Immunology, 13, 998470. [CrossRef]
• 52. Şen, A., Ertaş, B., Çevik, Ö., Yıldırım, A., Kayalı, D.G., Akakın, D., Bitiş, L., Şener, G. (2023). Cotinus coggygria Scop. attenuates acetic acid-ınduced colitis in rats by regulation of inflammatory mediators. Applied Biochemistry and Biotechnology, 195(11), 7021-7036. [CrossRef]
• 53. Zhang, H., Xia, B., Li, J., Zhao, Q., Chen, Z.T., Zhou, R., Wu, J. (2016). Expression and clinical significance of IL-17 and IL-17 receptor in ulcerative colitis. Journal of Huazhong University of Science and Technology, 36(1), 37-40. [CrossRef]
• 54. Zhu, Q., Zheng, P., Chen, X., Zhou, F., He, Q., Yang, Y. (2018). Andrographolide presents therapeutic effect on ulcerative colitis through the inhibition of IL-23/IL-17 axis. American Journal of Translational Research, 10(2), 465-473.[CrossRef]
• 55. Oliveira, R.G., Damazo, A.S., Antonielli, L.F., Miyajima, F., Pavan, E., Duckworth, C.A., Lima, J.C.D.S., Arunachalam, K., Martins, D.T.O. (2021). Dilodendron bipinnatum Radlk. extract alleviates ulcerative colitis induced by TNBS in rats by reducing inflammatory cell infiltration, TNF-α and IL-1β concentrations, IL-17 and COX-2 expressions, supporting mucus production and promotes an antioxidant effect. Journal of Ethnopharmacology, 269, 113735. [CrossRef]
• 56. Fitzpatrick, L.R., Small, J.S., Doblhofer, R., Ammendola, A. (2012). Vidofludimus inhibits colonic interleukin-17 and improves hapten-induced colitis in rats by a unique dual mode of action. The Journal of Pharmacology and Experimental Therapeutics, 342(3), 850-860. [CrossRef]
• 57. Zhang, M., Qiu, X., Zhang, H., Yang, X., Hong, N., Yang, Y., Chen, H., Yu, C. (2014). Faecalibacterium prausnitzii inhibits interleukin-17 to ameliorate colorectal colitis in rats. PloS one, 9(10), e109146. [CrossRef]
• 58. Fujino, S., Andoh, A., Bamba, S., Ogawa, A., Hata, K., Araki, Y., Bamba, T., Fujiyama, Y. (2003). Increased expression of interleukin 17 in inflammatory bowel disease. Gut, 52(1), 65-70. [CrossRef]
• 59. Jiang, W., Su, J., Zhang, X., Cheng, X., Zhou, J., Shi, R., Zhang, H. (2014). Elevated levels of Th17 cells and Th17-related cytokines are associated with disease activity in patients with inflammatory bowel disease. Inflammation Research: Official Journal of The European Histamine Research Society, 63(11), 943–950. [CrossRef]
• 60. Kang, G.D., Lim, S., Kim, D.H. (2015). Oleanolic acid ameliorates dextran sodium sulfate-induced colitis in mice by restoring the balance of Th17/Treg cells and inhibiting NF-κB signaling pathway. International Immunopharmacology, 29(2), 393-400. [CrossRef]
• 61. Qiu, W., Wu, B., Wang, X., Buchanan, M.E., Regueiro, M.D., Hartman, D.J., Schoen, R.E., Yu, J., Zhang, L. (2011). PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice. The Journal of Clinical Investigation, 121(5), 1722-1732. [CrossRef]
• 62. Ren, M.T., Gu, M.L., Zhou, X.X., Yu, M.S., Pan, H.H., Ji, F., Ding, C.Y. (2019). Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis. World Journal of Gastroenterology, 25(38), 5800-5813. [CrossRef]
• 63. Zheng, B., Ying, M., Xie, J., Chen, Y., Wang, Y., Ding, X., Hong, J., Liao, W., Yu, Q. (2020). A Ganoderma atrum polysaccharide alleviated DSS-induced ulcerative colitis by protecting the apoptosis/autophagy-regulated physical barrier and the DC-related immune barrier. Food & Function, 11(12), 10690-10699. [CrossRef]
• 64. Chen, X., Feng, H., El-Kott, A.F., Abd-Ella, E.M. (2020). Origanum vulgare L. leaves extract alleviates testis and sperm damages induced by finasteride: Biochemical, immunohistological and apoptosis genes based evidences. Andrologia, 52(11), e13823. [CrossRef]
• 65. Vujicic, M., Nikolic, I., Kontogianni, V.G., Saksida, T., Charisiadis, P., Orescanin-Dusic, Z., Blagojevic, D., Stosic-Grujicic, S., Tzakos, A. G., Stojanovic, I. (2015). Methanolic extract of Origanum vulgare ameliorates type 1 diabetes through antioxidant, anti-inflammatory and anti-apoptotic activity. The British Journal of Nutrition, 113(5), 770-782. [CrossRef]
• 66. Taha, M., Elazab, S.T., Abdelbagi, O., Saati, A.A., Babateen, O., Baokbah, T.A.S., Qusty, N.F., Mahmoud, M.E., Ibrahim, M.M., Badawy, A.M. (2023). Phytochemical analysis of Origanum majorana L. extract and investigation of its antioxidant, anti-inflammatory and immunomodulatory effects against experimentally induced colitis downregulating Th17 cells. Journal of Ethnopharmacology, 317, 116826. [CrossRef]
• 67. Shin, S.K., Cho, J.H., Kim, E.J., Kim, E.K., Park, D.K., Kwon, K.A., Chung, J.W., Kim, K.O., Kim, Y.J. (2017). Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model. World Journal of Gastroenterology, 23(25), 4559-4568. [CrossRef]
• 68. Xu, B.L., Zhang, G.J., Ji, Y.B. (2015). Active components alignment of Gegenqinlian decoction protects ulcerative colitis by attenuating inflammatory and oxidative stress. Journal of Ethnopharmacology, 162, 253–260. [CrossRef]
• 69. Wang, G., Xu, B., Shi, F., Du, M., Li, Y., Yu, T., Chen, L. (2019). Protective effect of methane-rich saline on acetic acid-ınduced ulcerative colitis via blocking the TLR4/NF-κB/MAPK pathway and promoting IL-10/JAK1/STAT3-mediated anti-inflammatory response. Oxidative Medicine and Cellular Longevity, 2019, 7850324. [CrossRef]
• 70. Bourgonje, A.R., Feelisch, M., Faber, K.N., Pasch, A., Dijkstra, G., van Goor, H. (2020). Oxidative stress and redox-modulating therapeutics in inflammatory bowel disease. Trends in Molecular Medicine, 26(11), 1034-1046. [CrossRef]
• 71. Han, Y., Ma, T.M., Lu, M.L., Ren, L., Ma, X.D., Bai, Z.H. (2014). Role of moxibustion in inflammatory responses during treatment of rat ulcerative colitis. World Journal of Gastroenterology, 20(32), 11297-11304. [CrossRef]
• 72. Sánchez-Muñoz, F., Fonseca-Camarillo, G., Villeda-Ramírez, M.A., Miranda-Pérez, E., Mendivil, E.J., Barreto-Zúñiga, R., Uribe, M., Bojalil, R., Domínguez-López, A., Yamamoto-Furusho, J.K. (2011). Transcript levels of Toll-Like Receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis. BMC Gastroenterology, 11, 138. [CrossRef]
• 73. Zhang, C., Hu, Y., Yuan, Y., Guo, J., Li, H., Li, Q., Liu, S. (2023). Liposome-embedded SOD attenuated DSS-induced ulcerative colitis in mice by ameliorating oxidative stress and intestinal barrier dysfunction. Food & Function, 14(9), 4392-4405. [CrossRef]
• 74. Hwang, J., Jin, J., Jeon, S., Moon, S.H., Park, M.Y., Yum, D.Y., Kim, J.H., Kang, J.E., Park, M.H., Kim, E.J., Pan, J.G., Kwon, O., Oh, G.T. (2020). SOD1 suppresses pro-inflammatory immune responses by protecting against oxidative stress in colitis. Redox Biology, 37, 101760. [CrossRef]
• 75. Yasui, K., Baba, A. (2006). Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation. Inflammation Research, 55(9), 359-363. [CrossRef]
• 76. Priyanthi, C., Sivakanesan, R. (2021). The total antioxidant capacity and the total phenolic content of rice using water as a solvent. International Journal of Food Science, 2021(1), 5268584. [CrosRef]
• 77. Herald, T.J., Gadgil, P., Tilley, M. (2012). High‐throughput micro plate assays for screening flavonoid content and DPPH‐scavenging activity in sorghum bran and flour. Journal of the Science of Food and Agriculture, 92(11), 2326-2331. [CrosRef]
• 78. Li, J., Zu, Y.G., Fu, Y.J., Yang, Y.C., Li, S., Li, Z.N., Wink, M. (2010). Optimization of microwave-assisted extraction of triterpene saponins from defatted residue of yellow horn (Xanthoceras sorbifolia Bunge.) kernel and evaluation of its antioxidant activity. Innovative Food Science & Emerging Technologies. 11, 637-643. [CrosRef]
• 79. Wojdyło, A., Oszmiański, J., Czemerys, R. (2007). Antioxidant activity and phenolic compounds in 32 selected herbs. Food Chemistry, 105(3), 940-949. [CrossRef]
• 80. Vuolo, M.M., Lima, V.S., Junior, M.R.M. (2019). Phenolic compounds: Structure, classification, and antioxidant power. In Bioactive Compounds. Woodhead Publishing, pp. 33-50. [CrossRef]
• 81. Ambriz-Pérez, D.L., Leyva-López, N., Gutierrez-Grijalva, E.P., Heredia, J.B. (2016). Phenolic compounds: Natural alternative in inflammation treatment. A Review. Cogent Food & Agriculture, 2(1), 1131412. [CrossRef]
• 82. Ríos, J.L., Recio, M.C., Maáñez, S., Giner, R.M. (2000). Natural triterpenoids as anti-inflammatory agents. Studies in Natural Products Chemistry, 22, 93-143. [CrossRef]
• 83. Miranda, R.S., de Jesus, B.D.S. M., da Silva Luiz, S.R., Viana, C.B., Adão Malafaia, C.R., Figueiredo, F.S., Carvalho, T.D.S.C., Silva, M.L., Londero, V.S., da Costa-Silva, T.A., Lago, J.H.G., Martins, R.C.C. (2022). Antiinflammatory activity of natural triterpenes-An overview from 2006 to 2021. Phytotherapy Research: PTR, 36(4), 1459-1506. [CrossRef]
• 84. Xue, J.C., Yuan, S., Meng, H., Hou, X.T., Li, J., Zhang, H.M., Chen, L.L., Zhang, C.H., Zhang, Q.G. (2023). The role and mechanism of flavonoid herbal natural products in ulcerative colitis. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 158, 114086. [CrossRef]
• 85. Dodda, D., Chhajed, R., Mishra, J. (2014). Protective effect of quercetin against acetic acid induced inflammatory bowel disease (IBD) like symptoms in rats: Possible morphological and biochemical alterations. Pharmacological Reports, 66(1), 169-173. [CrossRef]
• 86. Elgalil Mohamed Ahmed, A.A., Attia Mona, M.A., Abd-Elaziz Magdy, A.E.E., Abd Ellatif Rasha, A. (2022). Histological study of the effect of quercetin on experimentally induced ulcerative colitis in adult male albino rats. Tanta Medical Journal, 50(4), 285-295. [CrossRef]
• 87. Lin, Z., Gan, T., Huang, Y., Bao, L., Liu, S., Cui, X., Wang, H., Jiao, F., Zhang, M., Su, C., Qian, Y. (2022). Anti-Inflammatory activity of mulberry leaf flavonoids in vitro and in vivo. International Journal of Molecular Sciences, 23(14), 7694. [CrossRef]
• 88. Eshwarappa, R.S., Ramachandra, Y.L., Subaramaihha, S.R., Subbaiah, S.G., Austin, R.S., Dhananjaya, B. L. (2016). Anti-Lipoxygenase activity of leaf gall extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae). Pharmacognosy Research, 8(1), 78-82. [CrossRef]
• 89. Cuzzocrea, S., Rossi, A., Mazzon, E., Di Paola, R., Genovese, T., Muià, C., Caputi, A.P., Sautebin, L. (2005). 5-Lipoxygenase modulates colitis through the regulation of adhesion molecule expression and neutrophil migration. Laboratory Investigation; a Journal of Technical Methods And Pathology, 85(6), 808-822. [CrossRef]
• 90. Demirci, F., Teralı, K., Karadağ, A.E., Biltekin, S.N., Ak Sakallı, E., Demirci, B., Koşar, M., Başer, K.H. C. (2023). In vitro and in silico evaluation of ACE2 and LOX inhibitory activity of Origanum essential oils and carvacrol. Planta Medica, 89(8), 790-799. [CrossRef]
• 91. Sheta, N.M., Boshra, S.A. (2021). Fabrication and evaluation of celecoxib oral oleogel to reduce the inflammation of ulcerative colitis. AAPS PharmSciTech, 22(5), 180. [CrossRef]
• 92. Kourkoulis, P., Michalopoulos, G., Katifelis, H., Giannopoulou, I., Lazaris, A.C., Papaconstantinou, I., Karamanolis, G., Gazouli, M. (2020). Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity. European Journal of Gastroenterology & Hepatology, 32(9), 1106-1115. [CrossRef]
• 93. Xiao, Y., Li, B., Liu, J., Ma, X. (2018). Carvacrol ameliorates inflammatory response in interleukin 1β-stimulated human chondrocytes. Molecular Medicine Reports, 17(3), 3987-3992. [CrossRef]