Histopathological Restoration and Immunomodulatory Effects of Combined Plectranthus comosus and Allium sativum Extracts on Gastrointestinal Tissue in Salmonella typhi–Infected Wistar Rats
Keywords:
Salmonella typhi; Plectranthus comosus; Allium sativum; histopathology; gastrointestinal inflammationAbstract
Typhoid fever remains a major public health concern in endemic regions, with gastrointestinal inflammation and mucosal damage contributing significantly to disease severity and complications (Stanaway et al., 2021; Marchello et al., 2022). This study evaluated the in vivo therapeutic effectiveness of combined aqueous extracts of Plectranthus comosus and Allium sativum on intestinal histopathology and inflammatory responses in Salmonella typhi–infected rats. Male Wistar rats were orally infected with S. typhi and treated with combined plant extracts for 14 days at doses of 100, 150, and 200 mg/kg. Ciprofloxacin (10 mg/kg) served as a positive control. Histopathological assessment revealed severe villus atrophy, crypt hyperplasia, inflammatory infiltration, mucosal lesions, and necrosis in untreated infected rats. In contrast, extract-treated groups demonstrated dose-dependent restoration of intestinal architecture, with the 200 mg/kg dose producing near-normal villus height (470.0 ± 9.5 µm) and crypt depth (155.0 ± 5.2 µm), comparable to ciprofloxacin. Immunohistochemical analysis showed significant reductions in TNF-α and IL-6 staining intensities at the highest extract dose (TNF-α: 1.5 ± 0.1; IL-6: 1.6 ± 0.2), relative to untreated infected controls (TNF-α: 4.5 ± 0.2; IL-6: 4.8 ± 0.3). These findings were corroborated by qPCR analysis, which demonstrated marked downregulation of TNF-α and IL-6 mRNA expression. Overall, combined aqueous P. comosus and A. sativum extract therapy significantly attenuated intestinal inflammation and promoted mucosal recovery in S. typhi–infected rats, highlighting its potential as a complementary therapeutic strategy for typhoid-associated gastrointestinal pathology.
References
Abdulrahman, F. I., Suleiman, I. E., & Obidola, S. M. (2021). Phytochemical and antimicrobial properties of medicinal plants. Journal of Applied Sciences and Environmental Management, 25(3), 345–352.
Arreola, R., Quintero-Fabián, S., López-Roa, R. I., (2021). Immunomodulation and anti-inflammatory effects of garlic compounds. Journal of Immunology Research, 2021, Article 5522401. https://doi.org/10.1155/2021/5522401
Arreola, R., Quintero-Fabián, S., López-Roa, R. I., Flores-Gutierrez, E. O., Reves-Grajeda, J. p., Carrera-Quintanar, L., & Ortuno-Sahagun, D. (2015). Immunomodulation and anti-inflammatory effects of garlic compounds. Journal of Immunology Research, 2015, 401630. https://doi.org/10.1155/2015/401630
Bancroft, J. D., & Gamble, M. (2008). Theory and Practice of Histological Techniques (6th ed.). Churchill Livingstone.
Behnsen, J., Perez-Lopez, A., Nuccio, S.P., & Raffatellu, M. (2020). Exploiting host immunity: The Salmonella paradigm. Trends in Immunology, 41(5), 379-390. https://doi.org/10.1016/j.it.2020.02.007
Browne, A. J., Kashef Hamadani, B. H., Kumaran, E. A. P., Rao, P., Longbottom, J., Harriss, E., Hay, S. I. (2021). Drug-resistant enteric fever worldwide: a systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy, 76(6), 1484–1493.
Everest, P., Wain, J., Roberts, M., Rook, G., & Dougan, G. (2020). The molecular mechanisms of Salmonella-induced enteritis. Current Opinion in Gastroenterology, 36(1), 18–24.
Farhana, A., & Khan, M. A. (2021). Role of inflammatory cytokines in infectious diseases. Journal of Inflammation Research, 14, 1057–1070. https://doi.org/10.2147/JIR.S287114
Fàbrega, A., & Vila, J. (2019). Salmonella enterica serovar typhi skills to succeed in the host: Virulence and regulation. Clinical Microbiology Reviews, 32(4), e00066-18. https://doi.org/10.1128/CMR.00066-18
Festing, M. F. W., & Altman, D. G. (2002). Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR Journal, 43(4), 244–258.
Harborne, J. B. (1998). Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis (3rd ed.). Chapman & Hall.
Hooda, Y., Sajib, M. S. I., & Saha, S. (2023). Emergence of azithromycin-resistant Salmonella Typhi: A global health concern. Clinical Infectious Diseases, 76(2), e104–e111.
Jajere, S. M. (2019). A review of Salmonella enterica with particular focus on pathogenicity and antimicrobial resistance. Veterinary World, 12(4), 504–521.
Katana, L. K., Wanga, J., & Rono, S. J. (2025). In vitro antimicrobial activity of Plectranthus comosus and Allium sativum Extracts Against Salmonella typhi, Africa Journal of Technical and Vocational Education and Training, 10(1), 174-184.
Kiprono, C., Cheruiyot, K., & Ndunda, F. (2021). Phytochemical characterization and antibacterial activity of Plectranthus comosus. African Journal of Traditional, Complementary and Alternative Medicines, 18(2), 33–41.
Klemm, E. J., Shakoor, S., Page, A. J., Qamar, F.N., Judge, K., Saeed, D. K., Wong, V. K., Dallman, T. J., Nair, S., Baker, S., & Parkhill, J. (2021). Emergence of multidrug-resistant Salmonella typhi in endemic regions. Nature Microbiology, 6(5), 512–520.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2⁻ΔΔCt method. Methods, 25(4), 402–408.
Marchello, C. S., Hong, C. Y., & Crump, J. A. (2022). Global typhoid fever burden: a systematic review and meta-analysis. PLoS Neglected Tropical Diseases, 16(7), e0010689.
Marchello, C. S., Hong, C. Y., Crump, J. A. (2022). Global burden of non-typhoidal Salmonella invasive disease. The Lancet Infectious Diseases, 22(6), e117-e125. https://doi.org/10.1016/S1473-3099(21)00649-9
Mwangi, D., Kariuki, S., & Ngugi, M. (2020). Synergistic effects of combined medicinal plants on antimicrobial activity. Journal of Ethnopharmacology, 239, 111978.
Mwangi, J., Kamau, L., & Muita, P. (2022). Antibacterial properties of Plectranthus species against selected enteric pathogens. East African Journal of Science and Technology, 14(1), 24–33.
OECD (2008). Guidelines for the Testing of Chemicals: Repeated Dose 28-Day Oral Toxicity Study in Rodents. Organisation for Economic Co-operation and Development.
Ramos-Vara, J. A. (2005). Technical aspects of immunohistochemistry. Veterinary Pathology, 42(4), 405–426.
Salehi, B., Zucca, P., & Orhan, I. E. (2019). Antibacterial and immunomodulatory effects of Allium sativum: a comprehensive review. Nutrients, 11(5), 1022.
Salehi, B., Zucca, P., Sharifi-Rad, M., Pezzani, R., Rajabi, S., Setzer, W. N., Sharifi-Rad, J. (2019). Phytotherapeutics in cancer invasion and metastasis. Phytotherapy Research, 33(11), 2733-2748. https://doi.org/10.1002/ptr.6452
Sofowora, A. (2008). Medicinal Plants and Traditional Medicine in Africa (3rd ed.). Spectrum Books.
Stanaway, J. D., Reiner, R. C., Blacker, B. F., Goldberg, E. M., Khalil, I. A., Troeger, C. E., Andrews, J. R., Bhutta, Z. A., & Vos, T. (2021). The global burden of typhoid fever. The Lancet Infectious Diseases, 21(10), 1471–1482.
Stanaway, J. A., Reiner, R. C., Blacker, B. F., Goldberg, E. M., Khalil, I. A., Troeger, C. E., Andrews, J. R., Bhutta, Z. A., & Vos, T. (2019). The global burden of typhoid and paratyphoid fevers: A systematic analysis. The Lancet Infectious Diseases, 19(4), 369-381. https://doi.org/10.10116/s1473-3099(18)30685-6
Sultana, A., & Asif, M. (2020). Phytochemicals and their role in antimicrobial resistance: a review. Journal of Pharmacognosy and Phytochemistry, 9(2), 200–206.