Ephedra intermedia alleviates ethanol-mediated gastric ulcer in rats by anti-inflammatory and antioxidant mechanisms

Authors

  • Morteta H. Al-Medhtiy Department of Anatomy and Histology, Faculty of Veterinary Medicine, University of Kufa, Najaf, Iraq.
  • Mohammed T Mohammed Department of Microbiology, Faculty of veterinary medicine, University of Kufa, Najaf, Iraq.
  • Mohammed M. Hussein M. Raouf Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Erbil, Iraq.
  • Ayman M. Al-Qaaneh Department of Allied Health Sciences, Al-Balqa Applied University (BAU), Al-Salt, Jordan.
  • Ahmed A. j. Jabbar Department of Medical Laboratory Technology, Erbil Technical Health and Medical College, Erbil Polytechnic University, Erbil, Iraq. https://orcid.org/0000-0001-9689-4018
  • Musher Ismael Salih Department of Chemistry, Faculty of Science and Health, Koya University, Koya, Erbil, Iraq.
  • Rawaz Rizgar Hassan Department of Medical Laboratory Science, College of Science, Knowledge University, Erbil, Iraq.
  • Abdullah Othman Hassan Department of Medical Laboratory Science, College of Science, Knowledge University, Erbil, Iraq.
  • Mahmood Ameen Abdulla Department of Medical Analysis, Faculty of Applied Science, Tishk International University, Erbil, Iraq.
  • Shilan Farhad Mamand Department of Medical Microbiology, College of Science, Knowledge University, Erbil, Iraq.
  • Marwa M. Ameen Department of Medical Microbiology, College of Science, Cihan University-Erbil, Erbil, Iraq.
  • Parween Abdulsamad Ismail Department of Chemistry, College of Education, Salahaddin University, Erbil, Iraq.

DOI:

https://doi.org/10.21123/bsj.2024.10952

Keywords:

Antioxidant enzymes, Acute toxicity, Ephedra intermedia, stomach ulcer, histology

Abstract

Ephedra intermedia has been used as a traditional therapy for various health purposes including gastric disorders. To validate its traditional use, we investigated the acute toxicity and the gastro-protective effects of E. intermedia leaf extract (EILE) in ethanol-induced gastric injury in rats. Sprague Dawley rats were randomly separated into 5 groups: normal control (A) and ulcer rats (B) received orally 0.5% carboxymethyl cellulose (CMC); C, rats ingested with omeprazole 20mg/kg; D and E, rats ingested with 250 and 500mg/kg EILE, respectively. After 60 min, groups B-E received an oral dose of absolute ethanol to initiate a gastric ulcer. After another 60 min, the rats were anesthetized and sacrificed. The toxicity trial showed the absence of any toxic signs in rats exposed to up to 5 g/kg EILE. Ethanol ingestion led to significant gastric tissue penetration indicated by decreased mucus content, reduced gastric pH, and severe mucosal lesions. Rats treated with omeprazole or EILE had significantly less stomach tissue damage, indicated by a suppressive effect on ethanol-mediated gastric grazes, improvement of gastric mucus and pH, decreased edema, and leukocyte extravasation into the submucosal layer. EILE treatment caused a significant up-regulation of the endogenous antioxidant enzymes (SOD and CAT) and a reduction in MDA levels. Moreover, EILE-treated rats showed increased expression of PAS (glycoprotein) in the gastric epithelium and fundic glands. The gastro-protective effects of E. intermedia could be attributed to its positive augmentation of various stomach factors making it a potentially viable source of potent pharmaceuticals for ulcer amelioration.

References

Woolf A, Rehman RB RR. Gastric ulcer. Treasure Isl. StatPearls Publ. 2023;

Fu S, Chen J, Zhang C, Shi J, Nie X, Hu Y, et al. Gastroprotective effects of Periplaneta americana L. extract against ethanol-induced gastric ulcer in mice by suppressing apoptosis-related pathways. Front. Pharmacol. Frontiers Media SA; 2021;12: 798421.

Sistani Karampour N, Arzi A, Rezaie A, Pashmforoosh M, Kordi F. Gastroprotective Effect of Zingerone on Ethanol-Induced Gastric Ulcers in Rats. Medicina . 2019; 55(3)64-73. https://doi.org/10.3390/medicina55030064

Fazalda A, Quraisiah A, Nur Azlina MF. Antiulcer effect of honey in nonsteroidal anti-inflammatory drugs induced gastric ulcer model in rats: a systematic review. Evidence-Based Complement. Altern. Med. Hindawi; 2018;2018. https://doi.org/10.1155/2018/7515692.

Veilleux-Lemieux D, Castel A, Carrier D, Beaudry F, Vachon P. Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats. J. Am. Assoc. Lab. Anim. Sci. American Association for Laboratory Animal Science; 2013;52(5): 567–570.

Al-khateeb E, Al-Ani H, Al-Kadi K, Al-Obaidi E, Shalan N, Al-Rawi N. Investigation of the alkaloids of two Ephedra Spp. wildly grown in Iraq. Jordan J. Pharm. Sci. 2014;7(3) 191-198.

Zheng Q, Mu X, Pan S, Luan R, Zhao P. Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology. J Ethnopharmacol. 2024;319(Pt 2):117273. https://doi.org/10.1016/j.jep.2023.117273

Kilpatrick K, Pajak A, Hagel JM, Sumarah MW, Lewinsohn E, Facchini PJ, et al. Characterization of aromatic aminotransferases from Ephedra sinica Stapf. Amino Acids. 2016; 48: 1209-1220. https://doi.org/10.1007/s00726-015-2156-1.

Nasar MQ, Zohra T, Khalil AT, Ovais M, Ullah I, Ayaz M, et al. Extraction optimization, Total Phenolic-Flavonoids content, HPLC-DAD finger printing, antimicrobial, antioxidant and cytotoxic potentials of Chinese folklore Ephedra intermedia Schrenk & CA Mey. Braz J Pharm Sci. 2023; 58, e20989. http://dx.doi.org/10.1590/s2175-97902022e20989

Tang S, Ren J, Kong L, et al. Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity. Molecules. 2023; 28 (668) 1-22. http://dx.doi.org/10.3390/molecules28020663.

Almaimani G, Jabbar AAJ, Ibrahim IAA, Alzahrani AR, Bamagous GA, Almaimani RA, et al. Anise (Pimpinella anisum L.) attenuates azoxymethane-induced colorectal cancer by antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats. Environ. Sci. Pollut. Res. 2024;31(3): 4439–4452. https://doi.org/10.1007/s11356-023-31349-z

Gul R, Jan SU, Faridullah S, Sherani S, Jahan N. Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from Ephedra intermedia indigenous to Balochistan. Sci World J. 2017(1), p.5873648. https://doi.org/10.1155/2017/5873648

Fan X, Cao Y, Zeng M, Wang R, Liu Y, Xu C, et al. A New Lignan from the Herbaceous stems of Ephedra intermedia Schrenket CA Meyer. Rec Nat Prod. 2023; 17(2):293-299.

Shin MS, Lee J, Lee JW, Park SH, Lee IK, Choi JA, et al. Anti-inflammatory effect of artemisia argyi on ethanol-induced gastric ulcer: Analytical, in vitro and in vivo studies for the identification of action mechanism and active compounds. Plants. 2021; 10(2): 332-345. https://doi.org/10.3390/plants10020332

Raish M, Shahid M, Bin Jardan YA, et al. Gastroprotective Effect of Sinapic Acid on Ethanol-Induced Gastric Ulcers in Rats: Involvement of Nrf2/HO-1 and NF-κB Signaling and Antiapoptotic Role. Front Pharmacol 2021; 12: 622815. https://doi.org/10.3389/fphar.2021.622815

Liu Y, Sui D, Fu W, Sun L, Li Y, Yu P, et al. Protective effects of polysaccharides from Panax ginseng on acute gastric ulcers induced by ethanol in rats. Food Funct. 2021; 12(6): 2741-2749. https://doi.org/10.1039/d0fo02947e

Ahmed KA-A, Jabbar AAJ, M.Raouf MMH, et al. Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms. J Mol Histol. Epub ahead of print 2024. https://doi.org/10.1007/s10735-024-10211-7.

Nawahirsha S, Kurian G, Alexander T, Kurian S. Impact of alcohol on gastric mucosa in a population with high prevalence of Helicobacter pylori. Int. J. Adv. Med. 2021;8(6): 764.

Balogun SO, Damazo AS, de Oliveira Martins DT. Helicteres sacarolha A. St.-Hil. et al.: gastroprotective and possible mechanism of actions in experimental animals. J Ethnopharmacol. 2015; 166: 176-184. https://doi.org/10.1016/j.jep.2015.03.021

Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA. Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats. BMC Pharmacol Toxicol. 2019; 20(1)13-26. https://doi.org/10.1186/s40360-019-0292-z

Ben Ahmed Z, Yousfi M, Viaene J, Dejaegher B, Demeyer K, Heyden Y Vander. Four Pistacia atlantica subspecies (atlantica, cabulica, kurdica and mutica): A review of their botany, ethnobotany, phytochemistry and pharmacology. J. Ethnopharmacol. 2021;265: 113329. https://doi.org/10.1016/j.jep.2020.113329

Liang J, Dou Y, Wu X, Li H, Wu J, Huang Q, et al. Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis. Chem. Biol. Interact. Elsevier; 2018;283: 30–37. https://doi.org/10.1016/j.cbi.2018.01.014

Mohan S, Hobani YH, Shaheen E, Abou-Elhamd AS, abdelhaleem A, Alhazmi HA, et al. Girinimbine from curry leaves promotes gastro protection against ethanol induced peptic ulcers and improves healing via regulation of anti-inflammatory and antioxidant mechanisms. Food Funct. 2020; 11(4): 3493-3505. https://doi.org/10.1039/D0FO00053A

Simões S, Lopes R, Campos MCD, Marruz MJ, da Cruz MEM, Corvo L. Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation. Anim Model Exp Med. 2019; 2(2): 121-126. https://doi.org/10.1002/ame2.12060

Zhou D, Yang Q, Tian T, Chang Y, Li Y, Duan LR, et al. Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomed Pharmacother. 2020; 126-page. https://doi.org/10.1016/j.biopha.2020.110075

Gong G, Rigetu Zhao, Zhu Y, et al. Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats. kjpp 2021; 25: 403–411. https://doi.org/10.4196/kjpp.2021.25.5.403

Akanda MR, Kim IS, Ahn D, Tae HJ, Nam HH, Choo BK, et al. Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways. Int J Mol Sci . 2018; 19(2) 584-599. https://doi.org/10.3390/ijms19020584

Jabbar AAJ, Alamri ZZ, Abdulla MA, Salehen NA, Ibrahim IAA, Hassan RR, et al. Boric Acid (Boron) Attenuates AOM-Induced Colorectal Cancer in Rats by Augmentation of Apoptotic and Antioxidant Mechanisms. Biol Trace Elem Res. 2024;202(6):2702-2719. https://doi.org/10.1007/s12011-023-03864-0

Jan R, Khan M, Asaf S, Lubna, Asif S, Kim K-M. Bioactivity and therapeutic potential of kaempferol and quercetin: new insights for plant and human health. Plants. MDPI; 2022;11(19): 2623. https://doi.org/10.3390/plants11192623.

Khémiri I, Bitri L. Effectiveness of Opuntia ficus indica L. inermis seed oil in the protection and the healing of experimentally induced gastric mucosa ulcer. Oxid Med Cell Longev. 2019. https://doi.org/10.1155/2019/1568720

Ibeh LN, Ijioma SN, Emmanuel O, et al. Psidium guajava leaf extract improves gastrointestinal functions in rats and rabbits: an implication for ulcer and diarrhoea management. Biomarkers Biochem Indic Expo response, susceptibility to Chem 2021; 26: 737–746. https://doi.org/10.1080/1354750X.2021.

Guideline O. 423: Acute oral toxicity-acute toxic class method. OECD Guidelines for the Testing of Chemicals. Paris: OECD Publishing; 2001. 1–14 p.

Ahmed KA-A, Jabbar AAJ, Galali Y, M. Al-Qaaneh A, Akçakavak G, Salehen NA, et al. Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms. Ski. Res. Technol. John Wiley & Sons, Ltd; 2024;30(5): e13727. https://doi.org/10.1111/srt.13727

Shady NH, Abdullah HS, Maher SA, Albohy A, Elrehany MA, Mokhtar FA, et al. Antiulcer Potential of Psidium guajava Seed Extract Supported by Metabolic Profiling and Molecular Docking. Antioxidants. 2022; 11(7)1230. https://doi.org/10.3390/antiox11071230

Zhang J, Yin Y, Xu Q, et al. Integrated serum pharmacochemistry and investigation of the anti-gastric ulcer effect of Zuojin pill in rats induced by ethanol. Pharm Biol 2022; 60: 1417–1435. https://doi.org/10.1080/13880209.2022.2098345.

Vijayan DK, Sreerekha PR, Dara PK, et al. Antioxidant defense of fish collagen peptides attenuates oxidative stress in gastric mucosa of experimentally ulcer-induced rats. Cell Stress Chaperones 2022; 27: 45–54. https://doi.org/10.1007/s12192-021-01245-x.

Soni MG, Carabin IG, Griffiths JC, Burdock GA. Safety of ephedra: lessons learned. Toxicol Lett. 2004; 150(1): 97-110. https://doi.org/10.1016/j.toxlet.2003.07.006.

Hamoudi M, Amroun D, Boutefnouchet S, Bensouici C, Kaoula S, Harzallah D, et al. Phytochemical screening, in vitro antioxidant and enzyme inhibitory properties, and acute toxicity of extracts from the aerial parts of Ephedra nebrodensis, a source of bioactive compounds. Comb Chem High Throughput Screen. 2022; 25(6): 1058-1071. https://doi.org/10.2174/1386207324666210303094339.

Belazougui K, Mesrouk S, Mohammedi H, Akcha S, Aïnouz L, Mecherara-Idjeri SF. Phytochemical analysis, mineral composition, Assessment of antioxidant properties and cytotoxic potential of Ephedra alata. subsp. Alenda secondary metabolites. Food Biosci. 2023; 53: 102657. https://doi.org/10.1016/j.fbio.2023.102657

Taha MME, Abdelwahab SI, Mariod A, Abdulla MA, Nordin N, Jayapalan JJ, et al. Stem bark methanolic extract of Bauhinia thonningii (Schum) demonstrates gastroprotective properties against in vivo ethanol-induced injury. Funct. Food Sci. 2023;3(4): 26–40. https://doi.org/10.31989/ffs.v3i4.1048

Omar H, Nordin N, Hassan darvish P, Hajrezaie M, Azizan Syahadah AH, Fadaeinasab M, et al. Methanol leaf extract of actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats. Drug Des Devel Ther. 2017; 11. https://doi.org/10.2147/DDDT.S120564

Zaghlool SS, Abo-Seif AA, Rabeh MA, et al. Gastro-Protective and Anti-Oxidant Potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/Indomethacin-Induced Ulceration in Rats. Antioxidants (Basel, Switzerland); 8. Epub ahead of print October 2019. https://doi.org/10.3390/antiox8110512.

Hikino H, Kiso Y, Ogata M, Konno C, Aisaka K, Kubota H, et al. Pharmacological Actions of Analogues of Feruloylhistamine, an Imidazole Alkaloid of Ephedra Roots1. Planta Med. 1984; 50(06): 478-480.

Pirbalouti AG, Amirmohammadi M, Azizi S, Craker L. Healing effect of hydro-alcoholic extract of Ephedra pachyclada Boiss. in experimental gastric ulcer in rat. Acta Pol Pharm Res. 2013; 70(6): 1003-1009.

Ofusori AE, Moodley R, Jonnalagadda SB. Antiulcerogenic effects of Celosia trigyna plant extracts on ethanol-induced gastric ulcer in adult Wistar rats. J. Tradit. Complement. Med. 2020;10(6): 586–593. https://doi.org/https://doi.org/10.1016/j.jtcme.2019.11.004

Dhiyaaldeen SM, Alshawsh MA, Salama SM, Alwajeeh NSI, Al Batran R, Ismail S, et al. Potential activity of 3-(2-Chlorophenyl)-1-phenyl-propenonein accelerating wound healing in rats. Biomed Res. Int. 2014;2014. https://doi.org/10.1155/2014/792086

Gwaram NS, Musalam L, Ali HM, Abdulla MA, Shaker SA. Synthesis, spectral characterization and biological activity of Zn(II) complex with 2′-[1-(2-hydroxyphenyl) ethylidene]benzenesulfanohydrazide. Arab J Chem. 2016; 9: S1197-S1207. https://doi.org/10.1016/j.arabjc.2012.01.002

Saremi K, Rad SK, Khalilzadeh M, et al. In vivo acute toxicity and anti-gastric evaluation of a novel dichloro Schiff base: Bax and HSP70 alteration. Acta Biochim Biophys Sin (Shanghai); 52. Epub ahead of print 2020. https://doi.org/10.1093/abbs/gmz140.

Ben Lamine J, Boujbiha MA, Dahane S, Cherifa A Ben, Khlifi A, Chahdoura H, et al. α-Amylase and α-glucosidase inhibitor effects and pancreatic response to diabetes mellitus on Wistar rats of Ephedra alata areal part decoction with immunohistochemical analyses. Environ. Sci. Pollut. Res. Springer; 2019;26: 9739–9754. https://doi.org,10.1007/s11356-019-04339-3

Lim J, Lee H, Ahn J, Kim J, Jang J, Park Y, et al. The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice. J Ethnopharmacol. 2018; 225: 31-41. https://doi.org/10.1016/j.jep.2018.06.034

Ataei Azimi A, Delnavaz Hashemloian B, Amirinia A. The comparison of alkaloid, phenolic content and antioxidant activity of wild Ephedra intermedia (Schrenket) and in vitro culture of it’s explants. J Plant Process Funct. 2017; 6(21): 143-152.

Downloads

Issue

Section

article

How to Cite

1.
Ephedra intermedia alleviates ethanol-mediated gastric ulcer in rats by anti-inflammatory and antioxidant mechanisms. Baghdad Sci.J [Internet]. [cited 2024 Sep. 27];22(3). Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/10952