Journal of Ethnopharmacology and Toxicology | Volume 3 Issue 1 | Pages: 29-41 | Doi : 10.37446/jet/rsa/3.1.2025.29-41
Research Article
OPEN ACCESS | Published on : 31-May-2025

Antiulcer activity of freeze-dried leaf extracts of Rhus natalensis in ethanol-induced ulcer rat models


  • Janu G. Stower
  • University of Nairobi, Department of Medical Physiology, Faculty of Health Sciences. P.O Box 30197-00100, Nairobi, Kenya.

  • Hellen N. Kariuki
  • University of Nairobi, Department of Medical Physiology, Faculty of Health Sciences. P.O Box 30197-00100, Nairobi, Kenya.

  • Anne W. Muriithi
  • University of Nairobi, Department of Medical Physiology, Faculty of Health Sciences. P.O Box 30197-00100, Nairobi, Kenya.

  • Charles G. Githinji
  • University of Nairobi, Department of Medical Physiology, Faculty of Health Sciences. P.O Box 30197-00100, Nairobi, Kenya.

Abstract

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.

Keywords

Rhus natalensis, ethanol-induced gastric ulcer, peptic ulcer disease

References

  • Aebi, H. (1984). Catalase in vitro. In Methods in enzymology (Vol. 105, pp. 121-126). Academic press.

    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, 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 longevity2014(1), 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., Costa, A. P. M., Petreanu, M., ... & 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 ethnopharmacology184, 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., ... & Mathenge, S. G. (2006). Plant use of the Maasai of sekenani valley, Maasai mara, Kenya. Journal of ethnobiology and ethnomedicine2(1), 22. https://doi.org/10.1186/1746-4269-2-22

    Chari, S., Teyssen, S., & Singer, M. V. (1993). Alcohol and gastric acid secretion in humans. Gut34(6), 843-847.

    Clyne, M., & Ó Cróinín, T. (2025). Pathogenicity and virulence of Helicobacter pylori: A paradigm of chronic infection. Virulence16(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 experimentale10(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 Biochemistry131(4), 610–620. 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 Hepatology17(1), 101798. https://doi.org/10.4254/wjh.v17.i1.101798

    Gugliandolo, E., Cordaro, M., Fusco, R., Peritore, A. F., Siracusa, R., Genovese, T., ... & Crupi, R. (2021). Protective effect of snail secretion filtrate against ethanol-induced gastric ulcer in mice. Scientific Reports11(1), 3638. https://doi.org/10.1038/s41598-021-83170-8

    Gupta, A., Shetty, S., Mutalik, S., Mathew, E. M., Jha, A., Mishra, B., ... & Moorkoth, S. (2023). Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation. Heliyon9(10), e20406.
    https://doi.org/10.1016/j.heliyon.2023.e20406

    Hasanuzzaman, M., Bhuyan, M. B., Zulfiqar, F., Raza, A., Mohsin, S. M., Mahmud, J. A., ... & Fotopoulos, V. (2020). Reactive oxygen species and antioxidant defense in plants under abiotic stress: Revisiting the crucial role of a universal defense regulator. Antioxidants9(8), 681.  https://doi.org/10.3390/antiox9080681

    Iqbal, U., Malik, A., Sial, N. T., Mehmood, M. H., Uttra, A. M., Tulain, U. R., ... & Bathia, G. E. S. (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 Toxicology199, 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 investigation37(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 ethnopharmacology116(2), 370-376. https://doi.org/10.1016/j.jep.2007.11.041

    Kariuki, H. N., Kanui, T. I., Yenesew, A., Mbugua, P. M., & Patel, N. B. (2012). Antinociceptive activity of the root extracts of Rhus natalensis Kraus and Senna singueana. Phytopharmacology, 2(2), 312–317.
    http://erepository.uonbi.ac.ke/handle/11295/33009

    Katary, M. A., & Salahuddin, A. (2017). Gastroprotective effect of punicalagin against ethanol-induced gastric ulcer: the possible underlying mechanisms. Biomarkers Journal3(01-08).

    Katayama, Y., Toyoda, K., Kusano, Y., Suda, T., Adachi, S., Terauchi, I., ... & Tamano, M. (2017). Efficacy of vonoprazan-based second-line Helicobacter pylori eradication therapy in patients for whom vonoprazan-based first-line treatment failed. Gut66(4), 752-753. https://doi.org/10.1136/gutjnl-2016-312028

    Kigen, G., Kipkore, W., Wanjohi, B., Haruki, B., & Kemboi, J. (2017). Medicinal plants used by traditional healers in Sangurur, Elgeyo Marakwet County, Kenya. Pharmacognosy Research9(4), 333. 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. (2019). Peptic ulcer disease: a brief review of conventional therapy and herbal treatment options. Journal of clinical medicine8(2), 179. https://doi.org/10.3390/jcm8020179

    Lanas, A., & Chan, F. K. L. (2017). Peptic ulcer disease. The 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., ... & 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 biology57(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., & Brito, A. R. M. S. (2008). Should Anacardium humile St. Hil be used as an antiulcer agent? A scientific approach to the traditional knowledge. Fitoterapia79(3), 207-209. https://doi.org/10.1016/j.fitote.2007.11.006

    Marklund, S., & Marklund, G. (1974). Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European journal of biochemistry47(3), 469-474.

    Márquez-Flores, Y. K., Ayala-Velasco, J., Correa-Basurto, J., Estrada-Pérez, A., & Meléndez-Camargo, M. E. (2025). Peperomia campylotropa AW Hill: ethnobotanical, phytochemical, and metabolomic profile related to its gastroprotective activity. Molecules30(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 nutrition48(2), 107-111. https://doi.org/10.3164/jcbn.10-79

    Mohamed, T. A., Elshamy, A. I., Ibrahim, M. A., Atia, M. A., Ahmed, R. F., Ali, S. K., ... & Hegazy, M. E. F. (2021). Gastroprotection against rat ulcers by Nephthea sterol derivative. Biomolecules11(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., Raouf, M. M., Ismail, P. A., Mothana, R. A., ... & 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 Physiology52(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 Health48(1), 68. https://doi.org/10.1186/s41182-020-00256-1

    Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry95(2), 351-358.

    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 gastroenterologia51(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 supplements15(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 Gastroenterology31(7), 100044. 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 exasperataToxicology reports2, 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., ... & Sharifi‐Rad, J. (2018). Thymol, thyme, and other plant sources: Health and potential uses. Phytotherapy research32(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 Science11(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. Plants13(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 Therapeutics392(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., ... & Sharifi-Rad, J. (2018). Antiulcer agents: From plant extracts to phytochemicals in healing promotion. Molecules23(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., ... & 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 gastroenterology47(5), 540-552. https://doi.org/10.1007/s00535-012-0541-z

    Takagi, K., & Okabe, S. (1968). The effects of drugs on the production and recovery processes of the stress ulcer. The Japanese Journal of Pharmacology18(1), 9-18.

    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., ... & Lee, D. H. (2016). Centella asiatica leaf extract protects against indomethacin-induced gastric mucosal injury in rats. Journal of medicinal food19(1), 38-46. https://doi.org/10.1089/jmf.2015.3464