DOI QR코드

DOI QR Code

Protective effect of Evodiae Fructus extract in HCl/ethanol-induced gastritis mice

HCl/ethanol로 유도된 위염 마우스 모델에서 오수유 추출물의 보호 효과

  • IL-Ha Jeong (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Mi-Rae Shin (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Min Ju Kim (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Hui Yeon An (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Seong-Soo Roh (Department of Herbology, College of Korean Medicine, Daegu Haany University)
  • 정일하 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 김민주 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 안희연 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2024.06.05
  • Accepted : 2024.07.15
  • Published : 2024.08.31

Abstract

Purpose: This study investigated the anti-inflammatory effects of Evodiae Fructus (EF) on hydrochloric acid (HCl)/ethanol-induced gastritis, focusing on its impact on oxidative stress by analyzing inflammatory cytokines and inflammation-related factors. The total polyphenol and flavonoid contents were determined through in vitro experiments, while the radical scavenging activity was confirmed using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assays. Methods: In vivo experiments were conducted on rats divided into 5 groups (n = 7/in each group): normal group (Normal), 150 mM HCl/60% ethanol-induced gastritis group (Control), 150 mM HCl/60% ethanol-induced gastritis group administered 10 mg/kg sucralfate (SC), 150 mM HCl/60% ethanol-induced gastritis group administered EF at the doses of 100 mg/kg or 200 mg/kg (EF100 or EF200). The mice were pretreated with the extract (EF) or drug (SC), and after 1 hour, 150 mM HCl/60% ethanol (v/v) mixture was administered orally. Reactive oxygen species (ROS) levels, peroxynitrite (ONOO-), and pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1 beta were assessed in serum. Additionally, western blotting of the gastric tissues confirmed the expression of inflammation-related proteins. Results: EF alleviated the gastric mucosal damage caused by 150 mM HCl/60% ethanol. The assessment of oxidative stress in the serum showed that EF significantly reduced ROS and ONOO- levels and significantly decreased the levels of pro-inflammatory cytokines. Western blot analysis revealed that EF reduced ROS-generating nicotinamide adenine dinucleotide phosphate oxidase subunits, including gp91phox, p22phox, and p47phox. Additionally, EF mitigated the inflammation by inhibiting the mitogen-activated protein kinase signaling pathway. Conclusion: These results indicate that EF is a potential herbal medicine candidate for the treatment of oxidative stress-induced gastritis.

본 실험 결과, EF 열수 추출물이 항산화 활성뿐만 아니라, MAPK 신호 경로의 활성을 조절하고 전 염증성 사이토카인의 수준을 낮추는 것으로 나타났으며, 특히 EF 열수 추출물의 낮은 농도보다 높은 농도에서 더 뛰어난 효과를 나타내었다. 이는 EF 열수 추출물이 NADPH 산화효소, 항산화 단백질 및 염증성 단백질 발현을 조절하여 위 조직 내 급성 위염을 완화시킬 수 있음을 시사한다.

Keywords

Acknowledgement

This work was also supported by the Korea Foundation for Women in Science, Engineering, and Technology (WISET) Grant funded by the Ministry of Science and ICT (MSIT) under the Program for Returners into R&D. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2022R1A2B5B0100257112).

References

  1. McCarthy DM. Helicobacter pylori and non-steroidal anti-inflammatory drugs: does infection affect the outcome of NSAID therapy? Yale J Biol Med 1998; 71(2): 101-111.
  2. Srivastava A, Lauwers GY. Pathology of non-infective gastritis. Histopathology 2007; 50(1): 15-29. https://doi.org/10.1111/j.1365-2559.2006.02553.x
  3. Keshavarzian A, Fields JZ, Vaeth J, Holmes EW. The differing effects of acute and chronic alcohol on gastric and intestinal permeability. Am J Gastroenterol 1994; 89(12): 2205-2211.
  4. Bianchi Porro G, Parente F, Imbesi V, Montrone F, Caruso I. Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy. Gut 1996; 39(1): 22-26. https://doi.org/10.1136/gut.39.1.22
  5. Scheiman JM. The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage. Arthritis Res Ther 2013; 15 Suppl 3 (Suppl 3): S5.
  6. Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79(3): 629-661. https://doi.org/10.1021/acs.jnatprod.5b01055
  7. Kim YS, Park H, Song J, Lee D, Kim H. Anti-ulcer effects of HT074 on HCl/EtOH induced gastric injury. Korean J Herbol 2018; 33(4): 9-18.
  8. Al-Quraishy S, Othman MS, Dkhil MA, Abdel Moneim AE. Olive (Olea europaea) leaf methanolic extract prevents HCl/ethanol-induced gastritis in rats by attenuating inflammation and augmenting antioxidant enzyme activities. Biomed Pharmacother 2017; 91: 338-349. https://doi.org/10.1016/j.biopha.2017.04.069
  9. Lim JM, Song CH, Park SJ, Park DC, Cho HR, Jung GW, et al. Protective effects of a triple-fermented barley extract (FBe) against HCl/EtOH-induced gastric mucosa damage in mice. Food Sci Nutr 2018; 6(8): 2036-2046. https://doi.org/10.1002/fsn3.745
  10. Jin SE, Lee MY, Shin IS, Jeon WY, Ha H. Syzygium aromaticum water extract attenuates ethanol-induced gastric injury through antioxidant effects in rats. Mol Med Rep 2016; 14(1): 361-366. https://doi.org/10.3892/mmr.2016.5269
  11. Lee JA, Park HJ, Kim SH, Kim MJ, Kim KJ, Shin MR, et al. Evaluation of Evodiae Fructus extract on the chronic acid reflux esophagitis in rats. Korean J Herbol 2019; 34(2): 15-23.
  12. Chien CC, Wu MS, Shen SC, Ko CH, Chen CH, Yang LL, et al. Activation of JNK contributes to evodiamine-induced apoptosis and G2/M arrest in human colorectal carcinoma cells: a structure-activity study of evodiamine. PLoS One 2014; 9(6): e99729.
  13. Ogasawara M, Matsubara T, Suzuki H. Screening of natural compounds for inhibitory activity on colon cancer cell migration. Biol Pharm Bull 2001; 24(6): 720-723. https://doi.org/10.1248/bpb.24.720
  14. Xu ML, Li G, Moon DC, Lee CS, Woo MH, Lee ES, et al. Cytotoxicity and DNA topoisomerase inhibitory activity of constituents isolated from the fruits of Evodia officinalis. Arch Pharm Res 2006; 29(7): 541-547. https://doi.org/10.1007/BF02969262
  15. Sheu JR. Pharmacological effects of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa. Cardiovasc Drug Rev 1999; 17(3): 237-245. https://doi.org/10.1111/j.1527-3466.1999.tb00017.x
  16. Lee JA, Shin MR, Choi JW, Roh SS Effect of Toosendan Fructus on chronic acid reflux esophagitis rats. Korean J Herbol 2021; 36(3): 1-8.
  17. Yu X, Wu DZ, Yuan JY, Zhang RR, Hu ZB. Gastroprotective effect of Fructus Evodiae water extract on ethanol-induced gastric lesions in rats. Am J Chin Med 2006; 34(6): 1027-1035. https://doi.org/10.1142/S0192415X06004491
  18. Folin O, Denis W. On phosphotungstic-phosphomolybdic compounds as color reagents. J Biol Chem 1912; 12(2): 239-243. https://doi.org/10.1016/S0021-9258(18)88697-5
  19. Lister CE, Lancaster JE, Sutton KH, Walker JR. Developmental changes in the concentration and composition of flavonoids in skin of a red and a green apple cultivar. J Sci Food Agric 1994; 64(2): 155-161. https://doi.org/10.1002/jsfa.2740640204
  20. Islam T, Hasan MR, Roy A, Islam MS, Uddin MA, Islam MA, et al.. Screening of in-vitro antioxidant, brine shrimp lethality bioassay and antimicrobial activities of extracts of Bridelia retusa (L.) Spreng. Fruit. Int J Pharm 2015; 5(4): 1058-1067.
  21. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 1999; 26(9-10): 1231-1237. https://doi.org/10.1016/S0891-5849(98)00315-3
  22. Lee JS, Oh TY, Kim YK, Baik JH, So S, Hahm KB, et al. Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: stress-responsive transcription factors and MAP kinases as potential targets. Mutat Res 2005; 579(1-2): 214-224. https://doi.org/10.1016/j.mrfmmm.2005.03.027
  23. Syam AF, Sadikin M, Wanandi SI, Rani AA. Molecular mechanism on healing process of peptic ulcer. Acta Med Indones 2009; 41(2): 95-98.
  24. Handa O, Naito Y, Yoshikawa T. Redox biology and gastric carcinogenesis: the role of Helicobacter pylori. Redox Rep 2011; 16(1): 1-7. https://doi.org/10.1179/174329211X12968219310756
  25. Miyata K, Kamato T, Nishida A, Honda K. Studies on the mechanism for the gastric mucosal protection by famotidine in rats. Jpn J Pharmacol 1991; 55(2): 211-222. https://doi.org/10.1016/S0021-5198(19)39953-6
  26. Sohn YA, Hwang IY, Lee SY, Cho HS, Jeong CS. Protective effects of genipin on gastrointestinal disorders. Biol Pharm Bull 2017; 40(2): 151-154. https://doi.org/10.1248/bpb.b16-00545
  27. Lee JH, Lee DU, Jeong CS. Gardenia jasminoides Ellis ethanol extract and its constituents reduce the risks of gastritis and reverse gastric lesions in rats. Food Chem Toxicol 2009; 47(6): 1127-1131. https://doi.org/10.1016/j.fct.2009.01.037
  28. Funatsu T, Chono K, Hirata T, Keto Y, Kimoto A, Sasamata M. Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats. Eur J Pharmacol 2007; 554(1): 53-59. https://doi.org/10.1016/j.ejphar.2006.10.023
  29. Murat N, Gidener S, Koyuncuoglu M, Yilmaz O. The effect of nonsteroidal anti-inflammatory drugs on rat gastric mucosa. The role of endothelin. Saudi Med J 2007; 28(4): 612-616.
  30. Yao J. Tiao He Yi Wei Granule, a traditional Chinese medicine, against ethanol-induced gastric ulcer in mice. Evid Based Complement Alternat Med 2015; 2015: 647283.
  31. Zhao G, Yu YM, Kaneki M, Bonab AA, Tompkins RG, Fischman AJ. Simvastatin reduces burn injury-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway. Ann Surg 2015; 261(5): 1006-1012. https://doi.org/10.1097/SLA.0000000000000764
  32. Gobert AP, Wilson KT. Polyamine- and NADPH-dependent generation of ROS during Helicobacter pylori infection: a blessing in disguise. Free Radic Biol Med 2017; 105: 16-27. https://doi.org/10.1016/j.freeradbiomed.2016.09.024
  33. El-Benna J, Dang PM, Gougerot-Pocidalo MA, Marie JC, Braut-Boucher F. p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases. Exp Mol Med 2009; 41(4): 217-225. https://doi.org/10.3858/emm.2009.41.4.058
  34. Panday A, Sahoo MK, Osorio D, Batra S NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol 2015; 12(1): 5-23. https://doi.org/10.1038/cmi.2014.89
  35. Wu H, Ming W, Tan J, Lu Q, Mulmi Shrestha S, Li N, et al. Role of MKP-5-p38/MAPK pathway in Clopidogrel-induced gastric mucosal epithelial cells apoptosis and tight junction dysfunction. Am J Transl Res 2020; 12(5): 1741-1753.
  36. de Souza MC, Vieira AJ, Beserra FP, Pellizzon CH, Nobrega RH, Rozza AL. Gastroprotective effect of limonene in rats: influence on oxidative stress, inflammation and gene expression. Phytomedicine 2019; 53: 37-42. https://doi.org/10.1016/j.phymed.2018.09.027
  37. Yang Y, Kim SC, Yu T, Yi YS, Rhee MH, Sung GH, et al. Functional roles of p38 mitogen-activated protein kinase in macrophage-mediated inflammatory responses. Mediators Inflamm 2014; 2014: 352371.
  38. Garcia-Gonzalez MA, Aisa MA, Strunk M, Benito R, Piazuelo E, Jimenez P, et al. Relevance of IL-1 and TNF gene polymorphisms on interleukin-1β and tumor necrosis factor-α gastric mucosal production. Hum Immunol 2009; 70(11): 935-945.