Research Article
BibTex RIS Cite

Therapeutic Effects of Momordica charantia L. Ethanolic Extract on Acetic Acid-Induced Ulcerative Colitis in Rats

Year 2021, , 119 - 128, 17.12.2021
https://doi.org/10.26650/EurJBiol.2021.1016222

Abstract

Objective: This study aims to investigate the effect of Momordica charantia L. (MoC) ethanolic extract on ulcerative colitis (UC) and was explored in vitro and in vivo.

Materials and Methods: The rats were divided into control (C), saline-treated colitis (AA), MoC extract-treated colitis (AA+MoC), and sulfasalazine (SS)-treated colitis (AA+SS) groups. Colitis was induced by acetic acid. MoC extract, SS or saline were given to the related groups for 3 days. Interleukine-1β, malondialdehyde, glutathione levels, myeloperoxidase activity, bax/bcl-2 ratio, caspase-9 and caspase-3 levels were measured in colon and macroscopic and histopathologic examinations were done. Total phenolic/flavonoid content and biological activity of MoC were evaluated by in vitro analysis.

Results: Compared to the control group, with acetic acid application interleukin-1β levels, myeloperoxidase activity, malondialdehyde levels, bax/bcl-2 ratio, caspase-9 and caspase-3 levels were significantly upregulated, while glutathione levels were significantly decreased in the AA group. In contrast, MoC and SS treatments reduced interleukin-1β, malondialdehyde levels, myeloperoxidase activity, bax/bcl-2 ratio, and caspase-9 and caspase-3 levels. Glutathione levels increased upon MoC or SS treatment. Increased macroscopic and microscopic scoring with AA improved with MoC or SS treatment, but the MoC or SS treated groups had higher score values than the control. Also, in vitro results showed that MoC exhibited 2,2-diphenyl-1- picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activity as well as significant antilipoxygenase activity. In addition, MoC extract showed a potent anti-inflammatory activity compared to standard indomethacin.

Conclusion: Our biochemical, in vitro and histopathologic analysis indicate that MoC is likely to prove beneficial in UC therapy.

Thanks

We thanks to Deniz Mukaddes Turet for taking pictures of the colon and Seren Ede for helping arrangement of the manuscript.

References

  • 1. Yadav V, Varum F, Bravo R, Furrer E, Bojic D, Basit AW. Inflammatory bowel disease: exploring gut pathophysiology for novel therapeu-tic targets. Transl Res 2016; 176: 38-68. google scholar
  • 2. Karakoyun B, Ertaş B, Yüksel M, Akakin D, Çevik Ö, Şener G. Amelio-rative effects of riboflavin on acetic acid-induced colonic injury in rats. Clin Exp Pharmacol Physiol 2018; 45: 563-72. google scholar
  • 3. Fabia R, Willen R, Arrajab A, Andersson R, Ahren B, Bengmark S. Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. Eur Surg Res 1992; 24: 211-25. google scholar
  • 4. El-Akabawy G, El-Sherif NM. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-in-flammatory cytokines and oxidative stress. Biomed Pharmacother 2019; 111: 841-51. google scholar
  • 5. Shalkami AS, Hassan MIA, Bakr AG. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcer-ative colitis. Hum Exp Toxicol 2018; 37: 78-86. google scholar
  • 6. Hagiwara C, Tanaka M, Kudo H. Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requir-ing surgery. J Gastroenterol Hepatol 2002; 17: 758-64. google scholar
  • 7. Rosenberg LN, Peppercorn MA. Efficacy and safety of drugs for ul-cerative colitis. Expert Opin Drug Saf 2010; 9: 573-92. google scholar
  • 8. Saeed F, Afzaal M, Niaz B, Arshad Mu, Tufail T, Hussain MB, et al. Bitter Melon (Momordica Charantia): A Natural Healthy Vegetable. Int J Food Prop 2018; 21: 1270-90. google scholar
  • 9. Huang Ht, Zhang LJ, Huang HC, Hwang SY, Wu Cl, Lin YC, et al. Cucurbitane-type triterpenoids from the vines of Momordica cha-rantia and their anti-inflammatory activities. J Nat Prod 2020; 83: 1400-08. google scholar
  • 10. Ünal NG, Kozak A, Karakaya S, Oruç N, Barutçuoğlu B, Aktan Ç, et al. Anti-inflammatory effect of crude Momordica charantia l. ex-tract on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model in rat and the bioaccessibility of its carotenoid content. J Med Food 2020; 23: 641-8. google scholar
  • 11. Patel S, Patel T, Parmar K, Bhatt Y. Patel NM. Isolation, characteriza-tion and antimicrobial activity of charantin from Momordica cha-rantia linn. fruit. Int J Drug Dev Res 2010; 2: 629-34. google scholar
  • 12. Kumar R, Balaji S, Sripriya R, Nithya N, Uma TS, Sehgal PK. In vitro evaluation of antioxidants of fruit extract of Momordica charantia l. On fibroblasts and keratinocytes. J Agric Food Chem 2010; 58: 1518-22. google scholar
  • 13. Jia S, Shen M, Zhang F, Xie J. Recent advances in Momordica cha-rantia: functional components and biological activities. Int J Mol Sci 2017; 18: 2555. google scholar
  • 14. Gürbüz I, Akyüz Ç, Yeşilada E, Şener B. Anti-ulcerogenic effect of Momordica charantia l. fruits on various ulcer models in rats. J Eth-nopharmacol 2000; 71: 77-82. google scholar
  • 15. Lu HY, Lin BF. Wild bitter melon alleviates dextran sulphate sodi-um-induced murine colitis by suppressing inflammatory respons-es and enhancing intestinal regulatory t cells. J Funct Foods 2016; 23: 590-600. google scholar
  • 16. Zou Y, Chang SK, Gu Y, Qian SY. Antioxidant activity and phenolic compositions of lentil (Lens culinaris var. morton) extract and its fractions. J Agric Food Chem 2011; 59: 2268-76. google scholar
  • 17. Phosrithong N, Nuchtavorn N. Antioxidant and anti-inflammatory activities of Clerodendrum leaf extracts collected in Thailand. Eur J Integr Med 2016; 8(3): 281-85. google scholar
  • 18. Yildirim A, Şen A, Dogan A. Bitis L. Antioxidant and anti-inflamma-tory activity of capitula, leaf and stem extracts of tanacetum cilici-cum (boiss.) Grierson. Int J Second Metab 2019; 6: 211-22. google scholar
  • 19. Gao, X, Ohlander M, Jeppsson N, Björk L, Trajkovski V. Changes in Antioxidant Effects and Their Relationship to Phytonutrients in Fruits of Sea Buckthorn (Hippophae rhamnoides L.) during Matu-ration. J Agric Food Chem 2000; 48(5): 1485-90. google scholar
  • 20. Zhang R, Zeng Q, Deng Y, Zhang M, Wei Z, Zhang Y, et al. Phenolic profiles and antioxidant activity of litchipulp of different cultivars cultivated in Southern China. Food Chem. 2013; 136: 169-76. google scholar
  • 21. Buege JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol 1978; 52: 302-10. google scholar
  • 22. Beutler E. Red Cell Metabolism. A manual of biochemical methods. In B ergmeyen HV (ed.), annals of internal medicine 1975 2nd Ed. Issue 6. Grune & Stratton. google scholar
  • 23. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Investig Dermatol 1982; 78: 206-9. google scholar
  • 24. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measure-ment with the folin phenol reagent. J Biol Chem 1951;193: 265-75. google scholar
  • 25. Wurtz NR, Viet A, Shaw SA, Dilger A, Valente MN, Khan JA, et al. Po-tent triazolopyridine myeloperoxidase inhibitors. Acs Med Chem Lett 2018; 9: 1175-80. google scholar
  • 26. Chang CI, Chen CR, Liao YW, Cheng Hl, Chen YC, Chou CH. Cucur-bitane-type triterpenoids from Momordica charantia. J Nat Prod 2006; 69: 1168-71. google scholar
  • 27. Lin Kw, Yang Sc, Lin Cn. Antioxidant constituents from the stems and fruits of Momordica charantia. Food Chem 2011; 127: 609-14. google scholar
  • 28. Shivanagoudra SR, Perera WH, Perez JL, Athrey G, Sun Y, Jayapraka-sha GK, et al. Cucurbitane-type compounds from Momordica cha-rantia: Isolation, in vitro antidiabetic, anti-inflammatory activities and in silico modeling approaches. Bioorg Chem 2019; 87: 31-42. google scholar
  • 29. Randhawa PK, Singh K, Singh N, Jaggi AS. 2014. A review on chem-ical-induced inflammatory bowel disease models in rodents. Kore-an J Physiol Pharmacol 2014; 18: 279-88. google scholar
  • 30. Iseri SO, Ersoy Y, Ercan F, Yuksel M, Atukeren P, Gumustas K, et al. The effect of sildenafil, a phosphodiesterase-5 inhibitor, on ace-tic acid-induced colonic inflammation in the rat. J Gastroenterol Hepatol (Australia) 2009; 24: 1142-48. google scholar
  • 31. Kolgazi M, Uslu U, Yuksel M, Velioglu-Ogunc A, Ercan F, Alican I. The role of cholinergic anti-inflammatory pathway in acetic acid-in-duced colonic inflammation in the rat. Chem Biol Interact 2013; 205(1): 72-80. google scholar
  • 32. Soliman NA, Keshk WA, Rizk FH, Ibrahim MA. The possible amelio-rative effect of simvastatin versus sulfasalazine on acetic acid in-duced ulcerative colitis in adult rats. Chem Biol Interact 2019; 298: 57- 65. google scholar
  • 33. Tahan G, Gramignoli R, Marongiu F, Aktolga S, Cetinkaya A, Tahan V, et al. Melatonin expresses powerful anti-inflammatory and anti-oxidant activities resulting in complete improvement of acetic-ac- id-induced colitis in rats. Dig Dis Sci 2011; 56: 715-20. google scholar
  • 34. Semiz A, Ozgun Acar O, Cetin H, Semiz G, Sen, A. Suppression of inflammatory cytokines expression with Bitter melon (Momordi-ca charantia) in tnbs-instigated ulcerative colitis. J Transl Int Med 2020; 8: 177-87. google scholar
  • 35. Hossen I, Hua W, Ting L, Mehmood A, Jingyi S, Duoxia X, et al. Phy-tochemicals and inflammatory bowel disease: A review. Critical Reviews in Food Science and Nutrition 2020; 60(8): 1321-45. google scholar
  • 36. Guven B, Can M, Piskin O, Aydin BG, Karakaya K, Elmas O, et al. Flavonoids protect colon against radiation induced colitis. Regul Toxicol Pharmacol 2019; 104: 128-32. google scholar
  • 37. Yao J, Cao X, Zhang R, Li YX, Xu Zl, Zhang DG, et al. Protective effect of baicalin against experimental colitis via suppression of oxidant stress and apoptosis. Pharmacogn Mag 2016; 12: 225-34. google scholar
  • 38. Zhu L, Dai LM, Shen H, Gu PQ, Zheng K, Liu YJ, et al. Qing Chang Hua Shi granule ameliorate inflammation in experimental rats and cell model of ulcerative colitis through Mek/Erk signaling pathway. Biomed Pharmacother 2019; 116: 108967. google scholar
  • 39. Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiolo-gy 2000; 7: 153-63. google scholar
  • 40. Haeberlein SLB. Mitochondrial function in apoptotic neuronal cell death. Neurochem Res 2004; 29: 521-30. google scholar
  • 41. Tan KO, Fu NY, Sukumaran SK, Chan SL, Kang JH, Poon KL, et. Map-1 is a mitochondrial effector of bax. Proc Natl Acad Sci USA. 2005; 102(41): 14623-8. google scholar
  • 42. Cevik O, Akpinar H, Oba R, Cilingir OT, Ozdemir ZN, Cetinel S, et al. The effect of Momordica charantia intake on the estrogen re-ceptors ESRa/ESRp gene levels and apoptosis on uterine tissue in ovariectomy rats. Mol Biol Rep 2015; 42: 167-77. google scholar
Year 2021, , 119 - 128, 17.12.2021
https://doi.org/10.26650/EurJBiol.2021.1016222

Abstract

References

  • 1. Yadav V, Varum F, Bravo R, Furrer E, Bojic D, Basit AW. Inflammatory bowel disease: exploring gut pathophysiology for novel therapeu-tic targets. Transl Res 2016; 176: 38-68. google scholar
  • 2. Karakoyun B, Ertaş B, Yüksel M, Akakin D, Çevik Ö, Şener G. Amelio-rative effects of riboflavin on acetic acid-induced colonic injury in rats. Clin Exp Pharmacol Physiol 2018; 45: 563-72. google scholar
  • 3. Fabia R, Willen R, Arrajab A, Andersson R, Ahren B, Bengmark S. Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. Eur Surg Res 1992; 24: 211-25. google scholar
  • 4. El-Akabawy G, El-Sherif NM. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-in-flammatory cytokines and oxidative stress. Biomed Pharmacother 2019; 111: 841-51. google scholar
  • 5. Shalkami AS, Hassan MIA, Bakr AG. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcer-ative colitis. Hum Exp Toxicol 2018; 37: 78-86. google scholar
  • 6. Hagiwara C, Tanaka M, Kudo H. Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requir-ing surgery. J Gastroenterol Hepatol 2002; 17: 758-64. google scholar
  • 7. Rosenberg LN, Peppercorn MA. Efficacy and safety of drugs for ul-cerative colitis. Expert Opin Drug Saf 2010; 9: 573-92. google scholar
  • 8. Saeed F, Afzaal M, Niaz B, Arshad Mu, Tufail T, Hussain MB, et al. Bitter Melon (Momordica Charantia): A Natural Healthy Vegetable. Int J Food Prop 2018; 21: 1270-90. google scholar
  • 9. Huang Ht, Zhang LJ, Huang HC, Hwang SY, Wu Cl, Lin YC, et al. Cucurbitane-type triterpenoids from the vines of Momordica cha-rantia and their anti-inflammatory activities. J Nat Prod 2020; 83: 1400-08. google scholar
  • 10. Ünal NG, Kozak A, Karakaya S, Oruç N, Barutçuoğlu B, Aktan Ç, et al. Anti-inflammatory effect of crude Momordica charantia l. ex-tract on 2,4,6-trinitrobenzene sulfonic acid-induced colitis model in rat and the bioaccessibility of its carotenoid content. J Med Food 2020; 23: 641-8. google scholar
  • 11. Patel S, Patel T, Parmar K, Bhatt Y. Patel NM. Isolation, characteriza-tion and antimicrobial activity of charantin from Momordica cha-rantia linn. fruit. Int J Drug Dev Res 2010; 2: 629-34. google scholar
  • 12. Kumar R, Balaji S, Sripriya R, Nithya N, Uma TS, Sehgal PK. In vitro evaluation of antioxidants of fruit extract of Momordica charantia l. On fibroblasts and keratinocytes. J Agric Food Chem 2010; 58: 1518-22. google scholar
  • 13. Jia S, Shen M, Zhang F, Xie J. Recent advances in Momordica cha-rantia: functional components and biological activities. Int J Mol Sci 2017; 18: 2555. google scholar
  • 14. Gürbüz I, Akyüz Ç, Yeşilada E, Şener B. Anti-ulcerogenic effect of Momordica charantia l. fruits on various ulcer models in rats. J Eth-nopharmacol 2000; 71: 77-82. google scholar
  • 15. Lu HY, Lin BF. Wild bitter melon alleviates dextran sulphate sodi-um-induced murine colitis by suppressing inflammatory respons-es and enhancing intestinal regulatory t cells. J Funct Foods 2016; 23: 590-600. google scholar
  • 16. Zou Y, Chang SK, Gu Y, Qian SY. Antioxidant activity and phenolic compositions of lentil (Lens culinaris var. morton) extract and its fractions. J Agric Food Chem 2011; 59: 2268-76. google scholar
  • 17. Phosrithong N, Nuchtavorn N. Antioxidant and anti-inflammatory activities of Clerodendrum leaf extracts collected in Thailand. Eur J Integr Med 2016; 8(3): 281-85. google scholar
  • 18. Yildirim A, Şen A, Dogan A. Bitis L. Antioxidant and anti-inflamma-tory activity of capitula, leaf and stem extracts of tanacetum cilici-cum (boiss.) Grierson. Int J Second Metab 2019; 6: 211-22. google scholar
  • 19. Gao, X, Ohlander M, Jeppsson N, Björk L, Trajkovski V. Changes in Antioxidant Effects and Their Relationship to Phytonutrients in Fruits of Sea Buckthorn (Hippophae rhamnoides L.) during Matu-ration. J Agric Food Chem 2000; 48(5): 1485-90. google scholar
  • 20. Zhang R, Zeng Q, Deng Y, Zhang M, Wei Z, Zhang Y, et al. Phenolic profiles and antioxidant activity of litchipulp of different cultivars cultivated in Southern China. Food Chem. 2013; 136: 169-76. google scholar
  • 21. Buege JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol 1978; 52: 302-10. google scholar
  • 22. Beutler E. Red Cell Metabolism. A manual of biochemical methods. In B ergmeyen HV (ed.), annals of internal medicine 1975 2nd Ed. Issue 6. Grune & Stratton. google scholar
  • 23. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Investig Dermatol 1982; 78: 206-9. google scholar
  • 24. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measure-ment with the folin phenol reagent. J Biol Chem 1951;193: 265-75. google scholar
  • 25. Wurtz NR, Viet A, Shaw SA, Dilger A, Valente MN, Khan JA, et al. Po-tent triazolopyridine myeloperoxidase inhibitors. Acs Med Chem Lett 2018; 9: 1175-80. google scholar
  • 26. Chang CI, Chen CR, Liao YW, Cheng Hl, Chen YC, Chou CH. Cucur-bitane-type triterpenoids from Momordica charantia. J Nat Prod 2006; 69: 1168-71. google scholar
  • 27. Lin Kw, Yang Sc, Lin Cn. Antioxidant constituents from the stems and fruits of Momordica charantia. Food Chem 2011; 127: 609-14. google scholar
  • 28. Shivanagoudra SR, Perera WH, Perez JL, Athrey G, Sun Y, Jayapraka-sha GK, et al. Cucurbitane-type compounds from Momordica cha-rantia: Isolation, in vitro antidiabetic, anti-inflammatory activities and in silico modeling approaches. Bioorg Chem 2019; 87: 31-42. google scholar
  • 29. Randhawa PK, Singh K, Singh N, Jaggi AS. 2014. A review on chem-ical-induced inflammatory bowel disease models in rodents. Kore-an J Physiol Pharmacol 2014; 18: 279-88. google scholar
  • 30. Iseri SO, Ersoy Y, Ercan F, Yuksel M, Atukeren P, Gumustas K, et al. The effect of sildenafil, a phosphodiesterase-5 inhibitor, on ace-tic acid-induced colonic inflammation in the rat. J Gastroenterol Hepatol (Australia) 2009; 24: 1142-48. google scholar
  • 31. Kolgazi M, Uslu U, Yuksel M, Velioglu-Ogunc A, Ercan F, Alican I. The role of cholinergic anti-inflammatory pathway in acetic acid-in-duced colonic inflammation in the rat. Chem Biol Interact 2013; 205(1): 72-80. google scholar
  • 32. Soliman NA, Keshk WA, Rizk FH, Ibrahim MA. The possible amelio-rative effect of simvastatin versus sulfasalazine on acetic acid in-duced ulcerative colitis in adult rats. Chem Biol Interact 2019; 298: 57- 65. google scholar
  • 33. Tahan G, Gramignoli R, Marongiu F, Aktolga S, Cetinkaya A, Tahan V, et al. Melatonin expresses powerful anti-inflammatory and anti-oxidant activities resulting in complete improvement of acetic-ac- id-induced colitis in rats. Dig Dis Sci 2011; 56: 715-20. google scholar
  • 34. Semiz A, Ozgun Acar O, Cetin H, Semiz G, Sen, A. Suppression of inflammatory cytokines expression with Bitter melon (Momordi-ca charantia) in tnbs-instigated ulcerative colitis. J Transl Int Med 2020; 8: 177-87. google scholar
  • 35. Hossen I, Hua W, Ting L, Mehmood A, Jingyi S, Duoxia X, et al. Phy-tochemicals and inflammatory bowel disease: A review. Critical Reviews in Food Science and Nutrition 2020; 60(8): 1321-45. google scholar
  • 36. Guven B, Can M, Piskin O, Aydin BG, Karakaya K, Elmas O, et al. Flavonoids protect colon against radiation induced colitis. Regul Toxicol Pharmacol 2019; 104: 128-32. google scholar
  • 37. Yao J, Cao X, Zhang R, Li YX, Xu Zl, Zhang DG, et al. Protective effect of baicalin against experimental colitis via suppression of oxidant stress and apoptosis. Pharmacogn Mag 2016; 12: 225-34. google scholar
  • 38. Zhu L, Dai LM, Shen H, Gu PQ, Zheng K, Liu YJ, et al. Qing Chang Hua Shi granule ameliorate inflammation in experimental rats and cell model of ulcerative colitis through Mek/Erk signaling pathway. Biomed Pharmacother 2019; 116: 108967. google scholar
  • 39. Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiolo-gy 2000; 7: 153-63. google scholar
  • 40. Haeberlein SLB. Mitochondrial function in apoptotic neuronal cell death. Neurochem Res 2004; 29: 521-30. google scholar
  • 41. Tan KO, Fu NY, Sukumaran SK, Chan SL, Kang JH, Poon KL, et. Map-1 is a mitochondrial effector of bax. Proc Natl Acad Sci USA. 2005; 102(41): 14623-8. google scholar
  • 42. Cevik O, Akpinar H, Oba R, Cilingir OT, Ozdemir ZN, Cetinel S, et al. The effect of Momordica charantia intake on the estrogen re-ceptors ESRa/ESRp gene levels and apoptosis on uterine tissue in ovariectomy rats. Mol Biol Rep 2015; 42: 167-77. google scholar
There are 42 citations in total.

Details

Primary Language English
Journal Section Research Articles
Authors

Dilek Özbeyli 0000-0002-4141-6913

Ali Şen 0000-0002-2144-5741

Aslı Aykaç 0000-0002-4885-5070

Kerem Teralı This is me 0000-0002-9964-6383

Özlem Tuğçe Çilingir-kaya 0000-0002-2591-9174

İsmail Şenkardeş 0000-0002-2656-0319

Göksel Şener 0000-0001-7444-6193

Publication Date December 17, 2021
Submission Date October 30, 2021
Published in Issue Year 2021

Cite

AMA Özbeyli D, Şen A, Aykaç A, Teralı K, Çilingir-kaya ÖT, Şenkardeş İ, Şener G. Therapeutic Effects of Momordica charantia L. Ethanolic Extract on Acetic Acid-Induced Ulcerative Colitis in Rats. Eur J Biol. December 2021;80(2):119-128. doi:10.26650/EurJBiol.2021.1016222