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Study of the Effect and Underlying Mechanism of Enzyme-Treated Garlic Extract on a Lipopolysaccharide-Induced Acute Colitis Model

효소처리를 이용한 마늘 추출물이 Lipopolysaccharide 유발 급성 장염 모델에 미치는 효과 및 기전 연구

  • Min Ju Kim (Research Center for Herbal Convergence on Liver Disease, Daegu Haany University) ;
  • Mi-Rae Shin (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Hak Joo Choi (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Seong-Soo Roh (Dept. of Herbology, College of Korean Medicine, Daegu Haany University)
  • 김민주 (대구한의대학교 간질환한약융복합활용연구센터) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 최학주 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2023.11.30
  • Accepted : 2024.01.03
  • Published : 2023.12.30

Abstract

Objective: This study aims to explore the pharmacological effects and mechanisms of enzyme (Viscozyme)-treated garlic extract (EG) in an animal model of acute enteritis induced by lipopolysaccharide (LPS). Methods: The experiment included four subgroups: normal, control, EG200 (treated with 200 mg/kg EG), and EG400 (treated with 400 mg/kg EG). Drug administration lasted 3 days, followed by the induction of acute enteritis in all groups (except normal) through the intraperitoneal administration of 20 mg/kg of LPS 1 h after the last oral dose. Autopsy was conducted 24 h later to collect serum and colon tissue. Serum was analyzed for reactive oxygen species (ROS) and C-reactive protein (CRP), while Western blotting was performed on the colon tissue. Results: After analyzing the ROS and CRP levels in serum, the EG treatment group exhibited a significant decrease compared with the control group. The EG treatment group exhibited a significant decrease in the activation of the mitogen-activated protein kinases (MAPKs)/nuclear factor-kappa B p65 (NF-κB) pathway compared with the control group. EG administration significantly regulated apoptosis-related factors, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X, cysteine aspartyl-specific protease-3, and cytochrome C. Conclusions: EG treatment in mice with LPS-induced acute colitis reduced the ROS and CRP levels, suppressed the MAPKs/NF-κB pathway in the colon, and effectively alleviated acute enteritis by modulating apoptosis-related factors. Based on these findings, EG emerges as a promising candidate for the prevention and treatment of acute colitis, showing its potential therapeutic efficacy in this experimental model.

Keywords

Acknowledgement

본 연구는 중소벤처기업부의 기술개발사업[S3281126]과 정부 (과학기술정보통신부)의 재원으로 한국연구재단의 지원을 받아 수행되었습니다(No. 2018R1A5A2025272).

References

  1. Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity 2019;50(4):992-1006.  https://doi.org/10.1016/j.immuni.2019.03.017
  2. Arya VS, Kanthlal SK, Linda G. The role of dietary polyphenols in inflammatory bowel disease: A possible clue on the molecular mechanisms involved in the prevention of immune and inflammatory reactions. J Food Biochem 2020;44(11):e13369. 
  3. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 2015;12(12):720-7.  https://doi.org/10.1038/nrgastro.2015.150
  4. Kang YS, Kim SY, Jo MH, Kang HW, Lee JK, Lim YJ, et al. The Association between the Therapeutic Agent and the Compliance of the Patients with Inflammatory Bowel Diseases. Korean J Gastroenterol 2013;61(6):313-8.  https://doi.org/10.4166/kjg.2013.61.6.313
  5. Kim YK, Moon YH. A Study of the Effectiveness of Hwanggeum-tang and Gamchosasim-tang in the Mice Model of Inflammatory Bowel Disease. J Int Korean Med 2021;42(3):351-74.  https://doi.org/10.22246/jikm.2021.42.3.351
  6. Lee SH, Lee JA, Shin MR, Park HJ, Roh SS. Citrus unshiu Peel Attenuates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice due to Modulation of the PI3K/Akt Signaling Pathway and MAPK and NF-κB. Evid Based Complement Alternat Med 2022;2022:4041402. 
  7. Chen L, Li R, Wang Z, Zhang Z, Wang J, Qiao Y, et al. Lactate-utilizing bacteria ameliorates DSS-induced colitis in mice. Life Sci 2022;288:120179. 
  8. Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60(5):571-607.  https://doi.org/10.1136/gut.2010.224154
  9. Lin Z, Wu H, Fu Y, Dai S. Application of Herbaceous Medications for Inflammatory Bowel Disease as a Complementary and Alternative Therapy. Inflammatory bowel diseases 2019;25(12):1886-95.  https://doi.org/10.1093/ibd/izz190
  10. Kwon OS, Song JN, Yu HJ, Park HY. Effect of Fermented Garlic Extract on Adhesion of THP-1 Cells to Bovine Aortic Endothelial Cells. J Life Science 2017;27(5):553-60.  https://doi.org/10.5352/JLS.2017.27.5.553
  11. Son OG, Seo BI, Lee SH, Park SJ. The Study of DNA markers to identify of Allium sativum L. Kor J Herbology 2014;29(1):27-33.  https://doi.org/10.6116/kjh.2014.29.1.27
  12. Kim HJ, Han CH, Kim NY, Lee EK, Lee KN, Cho HE, et al. Effect of Garlic Extracts with Extraction Conditions on Antioxidant and Anticancer Activity. Korean J Oriental Physiology & Pathology 2010;24(1):111-7. 
  13. Jung SH, Lee SH, Ko KS. Effects of Various Garlic (Allium sativum) Extracts on Cholesterol Synthesis in HepG2 Cells. J Korean Soc Food Sci Nutr 2015;44(12):1779-84.  https://doi.org/10.3746/jkfn.2015.44.12.1779
  14. Kim KJ, Do JR, Kim HK. Antimicrobial, Antihypertensive and Anticancer Activities of Garlic Extracts. Korean J Food Sci Technol 2005;37(2):228-32. 
  15. Kim HK. The Effects of Anti-Thrombotic Activities and Cardiovascular Improvement of Fermented Garlic Extracts. JCCT 2020;6(2):567-72. 
  16. Tanrikulu Y, Sen Tanrikulu C, Kilinc F, Can M, Kokturk F. Effects of garlic oil (allium sativum) on acetic acid-induced colitis in rats: Garlic oil and experimental colitis. Ulus Travma Acil Cerrahi Derg 2020;26(4):503-8.  https://doi.org/10.14744/tjtes.2019.01284
  17. Shao X, Sun C, Tang X, Zhang X, Han D, Liang S, et al. Anti-Inflammatory and Intestinal Microbiota Modulation Properties of Jinxiang Garlic (Allium sativum L.) Polysaccharides toward Dextran Sodium Sulfate-Induced Colitis. J Agric Food Chem 2020;68(44):12295-309.  https://doi.org/10.1021/acs.jafc.0c04773
  18. Sun T, Tang J, Powers JR. Effect of pectolytic enzyme preparations on the phenolic composition and antioxidant activity of asparagus juice. J Agric Food Chem 2005;53(1):42-8.  https://doi.org/10.1021/jf0491299
  19. Sun T, Powers JR, Tang J. Effect of enzymatic macerate treatment on rutin content, antioxidant activity, yield, and physical properties of asparagus juice. J Food Sci 2007;72(4):S267-71.  https://doi.org/10.1111/j.1750-3841.2007.00345.x
  20. Kim Y, Oh J, Jang CH, Lim JS, Lee JS, Kim JS. In Vivo Anti-inflammatory Potential of Viscozyme®-Treated Jujube Fruit. Foods 2020;9(8):1033. 
  21. Hwang JT, Kim HJ, Ryuk JA, Jung DH, Ko BS. Efficiency of the Enzymatic Conversion of Flavone Glycosides Isolated from Carrot Leaves and Anti-Inflammatory Effects of Enzyme-Treated Carrot Leaves. Molecules 2023;28(11):4291. 
  22. Rama P, Vignesh A, Lakshmanan G. In Vitro Antioxidant Activity of Achyranthes Aspera Linn. Int J Med Pharm 2013;3(2):67-78. 
  23. Ali SF, LeBel CP, Bondy SC. Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 1992;13(3):637-48.  https://doi.org/10.1016/0892-0362(91)90081-7
  24. Chen G, Wen D, Shen L, Feng Y, Xiong Q, Li P, et al. Cepharanthine Exerts Antioxidant and Anti-Inflammatory Effects in Lipopolysaccharide (LPS)-Induced Macrophages and DSS-Induced Colitis Mice. Molecules 2023;28(16):6070. 
  25. Wei X, Li N, Wu X, Cao G, Qiao H, Wang J, et al. The preventive effect of Glycyrrhiza polysaccharide on lipopolysaccharide-induced acute colitis in mice by modulating gut microbial communities. Int J Biol Macromol 2023;239:124199. 
  26. Liu C, Yan X, Zhang Y, Yang M, Ma Y, Zhang Y, et al. Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy. J Nanobiotechnology 2022;20(1):206. 
  27. Pandey LK, Sharma KR. Analysis of Phenolic and Flavonoid Content, α-Amylase Inhibitory and Free Radical Scavenging Activities of Some Medicinal Plants. Scientific World Journal 2022;2022:4000707. 
  28. Nageen B, Sarfraz I, Rasul A, Hussain G, Rukhsar F, Irshad S, et al. Eupatilin: a natural pharmacologically active flavone compound with its wide range applications. J Asian Nat Prod Res 2020;22(1):1-16.  https://doi.org/10.1080/10286020.2018.1492565
  29. Chang JP, Doh ES, Kil KJ, Yang JK, Yun CW, Lee GH, et al. Antioxidative Activity of A. victorialis var. platyphyllum Extracts. Jour Korean For Soc 2011;100(3):408-16. 
  30. Chung JY, Kim CS. Antioxidant Activities of Domestic Garlic (Allium sativum L.) Stems from Different Areas. J Korean Soc Food Sci Nutr 2008;37(8):972-8.  https://doi.org/10.3746/jkfn.2008.37.8.972
  31. Shin JH, Choi DJ, Lee SJ, Cha JY, Sung NJ. Antioxidant Activity of Black Garlic (Allium sativum L.). J Korean Soc Food Sci Nutr 2008;37(8):965-71.  https://doi.org/10.3746/jkfn.2008.37.8.965
  32. Sands BE. Biomarkers of Inflammation in Inflammatory Bowel Disease. Gastroenterology 2015;149(5):1275-85.  https://doi.org/10.1053/j.gastro.2015.07.003
  33. Chang S, Malter L, Hudesman D. Disease monitoring in inflammatory bowel disease. World J Gastroenterol 2015;21(40):11246-59.  https://doi.org/10.3748/wjg.v21.i40.11246
  34. Yang S, Li F, Lu S, Ren L, Bian S, Liu M, et al. Ginseng root extract attenuates inflammation by inhibiting the MAPK/NF-κB signaling pathway and activating autophagy and p62-Nrf2-Keap1 signaling in vitro and in vivo. J Ethnopharmacol 2022;283:114739. 
  35. Kim MJ, Shin MR, Lee JA, Park SA, Park HJ, Lee JH, et al. Improvement Effect of Sprout of Coix lacryma-jobi var. mayuen Stapf Water Extract on DSS-Induced Ulcerative Colitis in Mice Kor J Herbol 2020;35(6):21-8. 
  36. Becker C, Watson AJ, Neurath MF. Complex roles of caspases in the pathogenesis of inflammatory bowel disease. Gastroenterology 2013;144(2):283-93.  https://doi.org/10.1053/j.gastro.2012.11.035
  37. Shin MR, Park HJ, Seo BI, Roh SS. New approach of medicinal herbs and sulfasalazine mixture on ulcerative colitis induced by dextran sodium sulfate. World J Gastroenterol 2020;26(35):5272-86. https://doi.org/10.3748/wjg.v26.i35.5272