This study aims to investigate the ulcer healing effects of freeze-dried leaf extracts of Rhus natalensis on Ethanol-induced gastric ulcer model in Sprague Dawley rats. Male Sprague Dawley rats (40), 250-300g were randomly assigned into 5 groups each with 8 animals as follows: negative control (1 ml / 200 g ethanol), positive control (20 mg / kg Esomeprazole + 1 ml /200 g ethanol), normal control (normal saline), low dose (150 mg / kg + 1 ml / 200 g ethanol), and high dose (300 mg / kg + 1 ml/ 200 g ethanol). To induce ulcers, absolute ethanol was administered on the first day at a dose of 1 ml / 200 g body weight by oral gavage to all groups except the normal control. Treatments were administered 1 hour after ethanol administration and once daily up to the 6th day. The ulcer healing effects were assessed by determining the total ulcer area, pH, and total acidity of stomach contents, volume of stomach secretions, levels of GSH, and levels of malondialdehyde in gastric tissue, catalase activity, and superoxide dismutase activity in gastric tissue. The data was reported as the mean ± SEM. There was a significant reduction in the total ulcer area in the treatment groups. The results showed a significant increase in the pH of gastric secretions in the treatment groups and also a dose dependent reduction in the total acidity of gastric secretions of the same groups. In this study, there was a decrease in the volume of gastric secretions in the treatment groups as compared to the negative control which showed an increase in the volume of secretions. The study showed an increase in cellular antioxidant activity in the treatment groups by increased catalase activity, superoxide dismutase (SOD) activity, and levels of reduced glutathione (GSH). The study shows that Rhus natalensis possesses ulcer healing effects. The effects are potentially due to reduced acidity of gastric contents, increased pH of gastric contents, reduced volume of secretions, and increased activity of cellular antioxidant systems; catalase, superoxide dismutase, and reduced glutathione.
Rhus natalensis, ethanol-induced gastric ulcer, peptic ulcer disease
Akdemir, F. N. E., Güler, M. C., Eraslan, E., Tanyeli, A., & Yildirim, S. (2024). Assessment of sinapic acid’s protective effects against ethanol-induced gastric ulcers in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology. https://doi.org/10.1007/s00210-024-03733-0
Albaayit, S. F. A., Abba, Y., Abdullah, R., & Abdullah, N. (2016). Prophylactic effects of Clausena excavata Burum. F. Leaf extract in ethanol-induced gastric ulcers. Drug Design, Development and Therapy, 10, 1973–1986. https://doi.org/10.2147/DDDT.S103993
Al-Qaisi, T. S., Jabbar, A. A. J., Raouf, M. M. H. M., Ismail, P. A.-S., Mothana, R. A., Al-Yousef, H. M., Hassan, R. R., Abdulla, M. A., Saleh, M. I., Awad, M., & Mahomoodally, M. F. (2025). The Gastroprotective Effects of Salvia indica L. and Selenium In Vivo Study. Biological Trace Element Research. https://doi.org/10.1007/s12011-025-04530-3
Ayala, A., Muñoz, M. F., & Argüelles, S. (2014). Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxidative Medicine and Cellular Longevity, 2014, 360438. https://doi.org/10.1155/2014/360438
Beiranvand, M., & Bahramikia, S. (2020). Ameliorating and protective effects mesalazine on ethanol-induced gastric ulcers in experimental rats. European Journal of Pharmacology, 888, 173573. https://doi.org/10.1016/j.ejphar.2020.173573
Boeing, T., da Silva, L. M., Somensi, L. B., Cury, B. J., Michels Costa, A. P., Petreanu, M., Niero, R., & de Andrade, S. F. (2016). Antiulcer mechanisms of Vernonia condensata Baker: A medicinal plant used in the treatment of gastritis and gastric ulcer. Journal of Ethnopharmacology, 184, 196–207. https://doi.org/10.1016/j.jep.2016.02.049
Bussmann, R. W., Gilbreath, G. G., Solio, J., Lutura, M., Lutuluo, R., Kunguru, K., Wood, N., & Mathenge, S. G. (2006). Plant use of the Maasai of Sekenani Valley, Maasai Mara, Kenya. Journal of Ethnobiology and Ethnomedicine, 2(1), 22. https://doi.org/10.1186/1746-4269-2-22
Chari, S., Teyssen, S., & Singer, M. V. (1993a). Alcohol and gastric acid secretion in humans. Gut, 34(6), 843–847. https://doi.org/10.1136/gut.34.6.843
Chari, S., Teyssen, S., & Singer, M. V. (1993b). Alcohol and gastric acid secretion in humans. Gut, 34(6), 843–847. https://doi.org/10.1136/gut.34.6.843
Clyne, M., & Ó Cróinín, T. (2025). Pathogenicity and virulence of Helicobacter pylori: A paradigm of chronic infection. Virulence, 16(1), 2438735. https://doi.org/10.1080/21505594.2024.2438735
Cohen, M. M. (1987). Role of endogenous prostaglandins in gastric secretion and mucosal defense. Clinical and Investigative Medicine. Medecine Clinique Et Experimentale, 10(3), 226–231.
Colak, H., Sarıyer, E. T., Yüksel, M., Polat, İ. Ö., Çikler, E., Öner, N., & Karakoyun, B. (2025). Bee bread shows therapeutic and protective effects by alleviating inflammation, oxidative stress, and apoptosis on acetic acid-induced gastric ulcer in rats: Effect of bee bread on gastric ulcer. Archives of Physiology and Biochemistry, 1–11. https://doi.org/10.1080/13813455.2025.2466191
Gou, G.-E., Li, T., Liu, C.-R., Meng, T., & Li, Y.-P. (2025). Potential mechanisms and therapeutic prospects of the association between Helicobacter pylori infection and metabolic dysfunction-associated steatohepatitis. World Journal of Hepatology, 17(1). https://doi.org/10.4254/wjh.v17.i1.101798
Gugliandolo, E., Cordaro, M., Fusco, R., Peritore, A. F., Siracusa, R., Genovese, T., D’Amico, R., Impellizzeri, D., Di Paola, R., Cuzzocrea, S., & Crupi, R. (2021). Protective effect of snail secretion filtrate against ethanol-induced gastric ulcer in mice. Scientific Reports, 11(1), 3638. https://doi.org/10.1038/s41598-021-83170-8
Gupta, A., Shetty, S., Mutalik, S., Chandrashekar H, R., K, N., Mathew, E. M., Jha, A., Mishra, B., Rajpurohit, S., Ravi, G., Saha, M., & Moorkoth, S. (2023). Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation. Heliyon, 9(10), e20406. https://doi.org/10.1016/j.heliyon.2023.e20406
Hasanuzzaman, M., Bhuyan, M. H. M. B., Zulfiqar, F., Raza, A., Mohsin, S. M., Mahmud, J. A., Fujita, M., & Fotopoulos, V. (2020). Reactive Oxygen Species and Antioxidant Defense in Plants under Abiotic Stress: Revisiting the Crucial Role of a Universal Defense Regulator. Antioxidants, 9(8), Article 8. https://doi.org/10.3390/antiox9080681
Iqbal, U., Malik, A., Sial, N. T., Mehmood, M. H., Uttra, A. M., Tulain, U. R., Erum, A., Fayyaz-ur-Rehman, M., Welson, N. N., Mahmoud, M. H., Alexiou, A., Papadakis, M., & El-Saber Bathia, G. (2025). Eucalyptol attenuates indomethacin-induced gastric ulcers in rats by modulating the ICAM-1, eNOS and COX/LOX pathways: Insights from in silico, in vitro and in vivo approaches. Food and Chemical Toxicology, 199, 115319. https://doi.org/10.1016/j.fct.2025.115319
Jenkins, H., Jenkins, R., & Patat, A. (2017). Effect of Multiple Oral Doses of the Potent CYP3A4 Inhibitor Clarithromycin on the Pharmacokinetics of a Single Oral Dose of Vonoprazan: A Phase I, Open-Label, Sequential Design Study. Clinical Drug Investigation, 37(3), 311–316. https://doi.org/10.1007/s40261-016-0488-6
Jeruto, P., Lukhoba, C., Ouma, G., Otieno, D., & Mutai, C. (2008). An ethnobotanical study of medicinal plants used by the Nandi people in Kenya. Journal of Ethnopharmacology, 116(2), 370–376. https://doi.org/10.1016/j.jep.2007.11.041
Kariuki, H. N., Kanui, & Et Al., T. (2012). Antinocieptive Activity Of The Root Extracts Of Rhus Natalensis Kraus And Senna Singueana. http://erepository.uonbi.ac.ke/handle/11295/33009
Katayama, Y., Toyoda, K., Kusano, Y., Suda, T., Adachi, S., Terauchi, I., Oka, S., Takahashi, M., & Tamano, M. (2017). Efficacy of vonoprazan-based second-line Helicobacter pylori eradication therapy in patients for whom vonoprazan-based first-line treatment failed. Gut, 66(4), 752–753. https://doi.org/10.1136/gutjnl-2016-312028
Kigen, G., Kipkore, W., Wanjohi, B., Haruki, B., & Kemboi, J. (2017a). Medicinal Plants Used by Traditional Healers in Sangurur, Elgeyo Marakwet County, Kenya. Pharmacognosy Research, 9(4), 333. https://doi.org/10.4103/pr.pr_42_17
Kigen, G., Kipkore, W., Wanjohi, B., Haruki, B., & Kemboi, J. (2017b). Medicinal Plants Used by Traditional Healers in Sangurur, Elgeyo Marakwet County, Kenya. Pharmacognosy Research, 9(4), 333–347. https://doi.org/10.4103/pr.pr_42_17
Kokwaro, J. O. (2009). Medicinal Plants of East Africa. University of Nairobi Press.
Kuna, L., Jakab, J., Smolic, R., Raguz-Lucic, N., Vcev, A., & Smolic, M. (2019a). Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. Journal of Clinical Medicine, 8(2), 179. https://doi.org/10.3390/jcm8020179
Kuna, L., Jakab, J., Smolic, R., Raguz-Lucic, N., Vcev, A., & Smolic, M. (2019b). Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. Journal of Clinical Medicine, 8(2), 179. https://doi.org/10.3390/jcm8020179
Lanas, A., & Chan, F. K. L. (2017). Peptic ulcer disease. Lancet (London, England), 390(10094), 613–624. https://doi.org/10.1016/S0140-6736(16)32404-7
Lu, S., Suo, F., Yu, W., & Wu, G. (2025). The therapeutic effect of different cumin essential oil fractions against gastric ulcer in rats. Journal of Food Science, 90(1), e17572. https://doi.org/10.1111/1750-3841.17572
Lu, S., Wu, D., Sun, G., Geng, F., Shen, Y., Tan, J., Sun, X., & Luo, Y. (2019). Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: Roles of antioxidation, anti-inflammation, and pro-survival. Pharmaceutical Biology, 57(1), 770–777. https://doi.org/10.1080/13880209.2019.1682620
Luiz-Ferreira, A., Cola-Miranda, M., Barbastefano, V., Hiruma-Lima, C. A., Vilegas, W., & Souza Brito, A. R. M. (2008). Should Anacardium humile St. Hil be used as an antiulcer agent? A scientific approach to the traditional knowledge. Fitoterapia, 79(3), 207–209. https://doi.org/10.1016/j.fitote.2007.11.006
Márquez-Flores, Y. K., Ayala-Velasco, J., Correa-Basurto, J., Estrada-Pérez, A., & Meléndez-Camargo, M. E. (2025). Peperomia campylotropa A.W. Hill: Ethnobotanical, Phytochemical, and Metabolomic Profile Related to Its Gastroprotective Activity. Molecules, 30(4), 772. https://doi.org/10.3390/molecules30040772
Matsui, H., Shimokawa, O., Kaneko, T., Nagano, Y., Rai, K., & Hyodo, I. (2011). The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. Journal of Clinical Biochemistry and Nutrition, 48(2), 107–111. https://doi.org/10.3164/jcbn.10-79
Mohamed, T. A., Elshamy, A. I., Ibrahim, M. A. A., Atia, M. A. M., Ahmed, R. F., Ali, S. K., Mahdy, K. A., Alshammari, S. O., Al-Abd, A. M., Moustafa, M. F., Farrag, A. R. H., & Hegazy, M.-E. F. (2021). Gastroprotection against Rat Ulcers by Nephthea Sterol Derivative. Biomolecules, 11(8), 1247. https://doi.org/10.3390/biom11081247
Mohammadi, Y., Tahergorabi, Z., Sharifzadeh, G. R., Rajabi Moghadam, M., & Zarban, A. (2024). Protective Effects of Some Graded Iranian Honey Samples Against Cold Water Immersion‐Induced Gastric Ulcers in Rats. Food Science & Nutrition, 12(12), 10211–10222. https://doi.org/10.1002/fsn3.4567
Mohammed, M. T., Al‐Qaisi, T. S., Jabbar, A. A. J., Raouf, M. M. H. M., Ismail, P. A., Mothana, R. A., Fantoukh, O. I., Hassan, R. R., Abdulla, M. A., Saleh, M. I., & Awad, M. (2025). Prophylactic Effects of Rhamnetin Flavonoid on Indomethacin‐Induced Gastric Ulceration by Modulating HSP 70/Bax, SOD / MDA and TNF ‐α/ IL ‐10. Clinical and Experimental Pharmacology and Physiology, 52(4), e70029. https://doi.org/10.1111/1440-1681.70029
Obakiro, S. B., Kiprop, A., Kowino, I., Kigondu, E., Odero, M. P., Omara, T., & Bunalema, L. (2020). Ethnobotany, ethnopharmacology, and phytochemistry of traditional medicinal plants used in the management of symptoms of tuberculosis in East Africa: A systematic review. Tropical Medicine and Health, 48, 68. https://doi.org/10.1186/s41182-020-00256-1
Oshima, T., & Miwa, H. (2016). Gastrointestinal mucosal barrier function and diseases. Journal of Gastroenterology, 51(8), 768–778. https://doi.org/10.1007/s00535-016-1207-z
Paguigan, N. D., Castillo, D. H. B., & Chichioco-Hernandez, C. L. (2014). Anti-ulcer activity of leguminosae plants. Arquivos De Gastroenterologia, 51(1), 64–67. https://doi.org/10.1590/s0004-28032014000100013
Palle, S., Kanakalatha, A., & Kavitha, C. N. (2018). Gastroprotective and Antiulcer Effects of Celastrus paniculatus Seed Oil Against Several Gastric Ulcer Models in Rats. Journal of Dietary Supplements, 15(4), 373–385. https://doi.org/10.1080/19390211.2017.1349231
Pan, Y., & Jiao, F.-Y. (2025). Helicobacter pylori infection and gastric microbiota: Insights into gastric and duodenal ulcer development. World Journal of Gastroenterology, 31(7). https://doi.org/10.3748/wjg.v31.i7.100044
Sabiu, S., Garuba, T., Sunmonu, T., Ajani, E., Sulyman, A., Nurain, I., & Balogun, A. (2015). Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin and Ficus exasperata. Toxicology Reports, 2, 261–267. https://doi.org/10.1016/j.toxrep.2015.01.002
Salama, N. R., Hartung, M. L., & Müller, A. (2013). Life in the human stomach: Persistence strategies of the bacterial pathogen Helicobacter pylori. Nature Reviews. Microbiology, 11(6), 385–399. https://doi.org/10.1038/nrmicro3016
Salehi, B., Mishra, A. P., Shukla, I., Sharifi-Rad, M., Contreras, M. D. M., Segura-Carretero, A., Fathi, H., Nasrabadi, N. N., Kobarfard, F., & Sharifi-Rad, J. (2018). Thymol, thyme, and other plant sources: Health and potential uses. Phytotherapy Research: PTR, 32(9), 1688–1706. https://doi.org/10.1002/ptr.6109
Sami, M., Azizi, S., Kheirandish, R., Ebrahimnejad, H., & Alizadeh, S. (2025). Protective Effects of Donkey Milk on Ethanol‐Induced Gastric Ulcer in Rat. Veterinary Medicine and Science, 11(1), e70156. https://doi.org/10.1002/vms3.70156
Sánchez-Mendoza, M. E., López-Lorenzo, Y., Torres-Morales, X. D. R., Cruz-Antonio, L., Arrieta-Baez, D., García-Machorro, J., & Arrieta, J. (2024). Gastroprotective Effect of Hexanic Extract of Heliotropium indicum Against Ethanol-Induced Gastric Lesions in a CD1 Mouse Model. Plants, 13(23), 3449. https://doi.org/10.3390/plants13233449
Satoh, H., Akiba, Y., Urushidani, T., & Kaunitz, J. D. (2025). Restraint stress exacerbates indomethacin-induced gastric antral ulcers by gastroparesis via activation of corticotropin-releasing factor 2 receptors in refed mice. The Journal of Pharmacology and Experimental Therapeutics, 392(3), 103381. https://doi.org/10.1016/j.jpet.2024.103381
Sharifi-Rad, M., Fokou, P. V. T., Sharopov, F., Martorell, M., Ademiluyi, A. O., Rajkovic, J., Salehi, B., Martins, N., Iriti, M., & Sharifi-Rad, J. (2018). Antiulcer Agents: From Plant Extracts to Phytochemicals in Healing Promotion. Molecules (Basel, Switzerland), 23(7), 1751. https://doi.org/10.3390/molecules23071751
Strand, D. S., Kim, D., & Peura, D. A. (2017). 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut and Liver, 11(1), 27–37. https://doi.org/10.5009/gnl15502
Sugano, K., Kontani, T., Katsuo, S., Takei, Y., Sakaki, N., Ashida, K., Mizokami, Y., Asaka, M., Matsui, S., Kanto, T., Soen, S., Takeuchi, T., Hiraishi, H., & Hiramatsu, N. (2012). Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: Results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial. Journal of Gastroenterology, 47(5), 540–552. https://doi.org/10.1007/s00535-012-0541-z
Teshome, Y., Mekonen, W., Birhanu, Y., & Sisay, T. (2019). The association between ABO blood group distribution and peptic ulcer disease: A cross-sectional study from Ethiopia. Journal of Blood Medicine, 10, 193–197. https://doi.org/10.2147/JBM.S209416
Weschawalit, S., Thongthip, S., Phutrakool, P., & Asawanonda, P. (2017). Glutathione and its antiaging and antimelanogenic effects. Clinical, Cosmetic and Investigational Dermatology, 10, 147–153. https://doi.org/10.2147/CCID.S128339
Zheng, H.-M., Choi, M.-J., Kim, J. M., Cha, K. H., Lee, K. W., Park, Y. H., Hong, S.-S., & Lee, D. H. (2016). Centella asiatica Leaf Extract Protects Against Indomethacin-Induced Gastric Mucosal Injury in Rats. Journal of Medicinal Food, 19(1), 38–46. https://doi.org/10.1089/jmf.2015.3464
