SEX-SPECIFIC SUB-ACUTE TOXICITY AND IMMUNOMODULATORY PROFILE OF A NIGERIAN POLYHERBAL SUPPLEMENT (NAPHERBS) IN ALBINO WISTAR RATS
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https://doi.org/10.54548/सार
NaPherbs, a Nigerian-based polyherbal supplement compounded with Moringa oleifera, Vernonia amygdalina, Garcinia kola, etc. is consumed locally as an immune-boosting nutraceutical. In this study, we investigated its preliminary immune-boosting mechanisms and sub-acute toxicity profile in both male and female albino Wistar rats. A total of 40 Wistar rats (20 males and 20 females) were randomly allotted to 5 experimental groups (n=8, 4 males and 4 females); control, 125, 250, 500 and 1000 mg/kg/day of NaPherbs for 30 consecutive days. The animals were anesthetized, and cardiac puncture was used to obtain serum for biochemical assays such as the serum lipid profile, immunoglobulins concentration, proinflammatory cytokines’ concentration and liver function enzymes; and whole blood for hematological assessment. In vivo antioxidant assays were carried out also on the liver homogenates, while the liver and kidneys were examined histologically in both male and female animals. There was a dose-dependent increase in the neutrophil: leucocyte ratio in the female animals. This has been linked to physiological stress, underlying disease condition and most recently a risk factor for early onset chronic kidney disease (CKD). NaPherbs did not pose any major cardiovascular risk across the groups, and there seemed to be some level of cardioprotection judging from the reduction in low-density lipoprotein cholesterol (LDL-c), triglyceride (TG) and total cholesterol (TC) observed in both sexes. The antioxidant indices assayed for were not significantly (P<0.05) affected by NaPherbs treatment, except for the catalase enzyme which was significantly increased in the female animals. As a purported immune-boosting supplement, we carried out a preliminary investigation on its effect on pro-inflammatory cytokines and immunoglobulins. NaPherbs did not significantly (P<0.05) alter these indices. Histological examination of the liver and kidneys showed that NaPherbs did not cause any major deleterious effect to these organs, except for mild infiltration of the sinusoids with inflammatory cells in the hepatocyte. NaPherbs showed a consistent profile of safety across the animals and doses considered in this study. However, further immunologic assays must be explored to validate its immune boosting claims and more specific toxicity assays must be employed to focus more on neurotoxicity, nephrotoxicity and gonadotoxicity in both sexes.
##submission.citations##
Adeniyi, T., Moronkeji, A., & Ekundina, V. (2023). Histological evaluation of the liver, kidney, and testes of adult male Wistar rats exposed to heavy metals-contaminated waterways. Medical Laboratory Journal, 17(5), 4-8.
Adeyemo-Salami, O. A., & Ewuola, E. O. (2015). Hematological effects of repeated graded doses of the methanol extract of Paullinia pinnata (Linn.) leaves in Wistar albino rats. Pharmacognosy Research, 7(Suppl 1), S34.
Afolabi, S. O., Olorundare, O., Akanbi, O. B., Bello, M. K., Njan, A., Agede, O. A., ... & Ibiyemi, S. (2023). GC/MS Analysis and a 30-day Toxicological Evaluation of a Nigerian Immunomodulatory Polyherbal Supplement (PHS). Pharmacology and Toxicology of Natural Medicines (ISSN: 2756-6838), 3(2), 1-14.
Akanbi, O. B., Ola-Fadunsin, S. D., Yahaya, S., Kaye, R., & Shamaki, R. (2022). Parasites and parasitic diseases of laboratory animals in Plateau State Nigeria: The zoonotic implications. Journal of Parasitic Diseases, 46(1), 56-63.
Anwar, S., Alrumaihi, F., Sarwar, T., Babiker, A. Y., Khan, A. A., Prabhu, S. V., & Rahmani, A. H. (2024). Exploring therapeutic potential of catalase: Strategies in disease prevention and management. Biomolecules, 14(6), 697.
Asala, T. M., Abatan, M. O., Salami, S. A., Baba-Onoja, O. O., Akanbi, O. B., Rowaiye, A. B & Ada, G. (2021). The ameliorative effect of the solvent extracts of Ocimum basilicum against acetaminophen-induced liver damage in albino rats. Journal of Phytomedicine and Therapeutics, 20(1), 581-597.
Avwioro, O. G. (2010). Histochemistry and tissue pathology, principles and techniques. Nigeria: Claverianum.
Bano, N., & Najam, R. (2019). Histopathological and biochemical assessment of liver damage in albino Wistar rats treated with cytotoxic platinum compounds in combination with 5-fluorouracil. Archives of Medical Science, 15(4), 1092-1103.
Barbalato, L., & Pillarisetty, L. S. (2022). Histology, red blood cell. StatPearls [internet].
Bhol, N. K., Bhanjadeo, M. M., Singh, A. K., Dash, U. C., Ojha, R. R., Majhi, S. & Jena, A. B. (2024). The interplay between cytokines, inflammation, and antioxidants: mechanistic insights and therapeutic potentials of various antioxidants and anti-cytokine compounds. Biomedicine & Pharmacotherapy, 178, 117177.
Chandimali, N., Bak, S. G., Park, E. H., Lim, H. J., Won, Y. S., Kim, E. K., ... & Lee, S. J. (2025). Free radicals and their impact on health and antioxidant defenses: A review. Cell death discovery, 11(1), 19.
Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., ... & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198.
Chmielewski, P. P., Strzelec, B., Mozdziak, P., & Kempisty, B. (2025). Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Long-Term Survival in Older Adults at a Mental Health Care Center: A Historical Cohort Analysis. Journal of Clinical Medicine, 14(7), 2509.
Dayimu, A., Wang, C., Li, J., Fan, B., Ji, X., Zhang, T., & Xue, F. (2019). Trajectories of lipids profile and incident cardiovascular disease risk: a longitudinal cohort study. Journal of the American Heart Association, 8(21), e013479.
Dubale, S., Usure, R. E., Mekasha, Y. T., Hasen, G., Hafiz, F., Kebebe, D., & Suleman, S. (2025). Traditional herbal medicine legislative and regulatory framework: a cross-sectional quantitative study and archival review perspectives. Frontiers in Pharmacology, 16, 1475297.
Elkordy, A. A., Haj-Ahmad, R. R., Awaad, A. S., & Zaki, R. M. (2021). An overview on natural product drug formulations from conventional medicines to nanomedicines: Past, present and future. Journal of Drug Delivery Science and Technology, 63, 102459.
Gamil, N. M., Elsayed, H. A., Hamed, R. M., Salah, E. T., Ahmed, A. M., Mostafa, H. A., ... & Abou-Hussein, D. (2025). Insights from herb interactions studies: a foundational report for integrative medicine. Future Journal of Pharmaceutical Sciences, 11(1), 46.
Getie, A., Ayenew, T., Amlak, B. T., Gedfew, M., Akalu, T. Y., Edmealem, A. & Yilak, G. (2025). Abnormal lipid profile and its associated factors among chronically ill patients in Ethiopia: systematic review and meta-analysis. Critical Public Health, 35(1), 2519778.
Guo, M., Wang, Z., Yang, R., Liu, K., Zeng, J., & An, T. (2022). High neutrophil/lymphocyte ratio and low lymphocyte percentage are independent risk factors for new-onset ckd. Clinical Immunology Communications, 2, 165-171.
Kale, O. E., Awodele, O., & Akindele, A. J. (2019). Subacute and subchronic oral toxicity assessments of Acridocarpus smeathmannii (DC.) Guill. & Perr. root in Wistar rats. Toxicology Reports, 6, 161-175.
Klimpel, G. R. (1996). Immune defenses. Medical Microbiology. 4th edition.
Klingler, J., Weiss, S., Itri, V., Liu, X., Oguntuyo, K. Y., Stevens, C., ... & Hioe, C. E. (2021). Role of immunoglobulin M and A antibodies in the neutralization of severe acute respiratory syndrome coronavirus 2. The Journal of infectious diseases, 223(6), 957-970.
Lee, T. H., Kim, W. R., & Poterucha, J. J. (2012). Evaluation of elevated liver enzymes. Clinics in liver disease, 16(2), 183-198.
Mitruka BM, Rawnsley HM. New York: Massom Publishers Inc; 1977. Clinical Biochemical and Haematological Reference Values in Normal Experimental Animals.
Moussavi, N., Mounkoro, P. P., Dembele, S. M., Ballo, N. N., Togola, A., Diallo, D., & Paulsen, B. S. (2024). Polyherbal Combinations Used by Traditional Health Practitioners against Mental Illnesses in Bamako, Mali, West Africa. Plants, 13(3), 454.
Nandi, A., Yan, L. J., Jana, C. K., & Das, N. (2019). Role of catalase in oxidative stress‐and age‐associated degenerative diseases. Oxidative medicine and cellular longevity, 2019(1), 9613090.
Nie, J., Zhou, L., Tian, W., Liu, X., Yang, L., Yang, X., ... & Wei, J. (2025). Deep insight into cytokine storm: from pathogenesis to treatment. Signal Transduction and Targeted Therapy, 10(1), 112.
Okaiyeto, K., & Oguntibeju, O. O. (2021). African herbal medicines: Adverse effects and cytotoxic potentials with different therapeutic applications. International journal of environmental research and public health, 18(11), 5988.
Patel, A., & Jialal, I. (2023). Biochemistry, immunoglobulin A. In StatPearls [Internet]. StatPearls Publishing.
Puri, V., Nagpal, M., Singh, I., Singh, M., Dhingra, G. A., Huanbutta, K., ... & Sangnim, T. (2022). A comprehensive review on nutraceuticals: therapy support and formulation challenges. Nutrients, 14(21), 4637.
Romero-García, P. A., Ramirez-Perez, S., Miguel-González, J. J., Guzmán-Silahua, S., Castañeda-Moreno, J. A., Komninou, S., & Rodríguez-Lara, S. Q. (2024). Complementary and alternative medicine (CAM) practices: A narrative review elucidating the impact on healthcare systems, mechanisms and paediatric applications. In Healthcare (Vol. 12, No. 15, p. 1547). MDPI.
Sharma, S. R., & Sharma, B. (2022). Immunity: A Step-by-Step Overview. Homœopathic Links, 35(01), 048-055.
Soares, C. L. R., Wilairatana, P., Silva, L. R., Moreira, P. S., Barbosa, N. M. M. V., da Silva, P. R. & Felipe, C. F. B. (2023). Biochemical aspects of the inflammatory process: A narrative review. Biomedicine & Pharmacotherapy, 168, 115764.
Taqiuddin, R., Gupta, H., Sufian, Z., Kamaluddin, K., Mohamed, Y. A. E. R., Khan, A., ... & Mateen, M. A. (2024). Cardiovascular risk evaluation using lipid profile and blood pressure among obese and non-obese individuals in India. Bioinformation, 20(7), 723.
Vignesh, A., Amal, T. C., Sarvalingam, A., & Vasanth, K. (2024). A review on the influence of nutraceuticals and functional foods on health. Food Chemistry Advances, 5, 100749.
Wang, L., Shao, Z., Wang, X., Lu, W., & Sun, H. (2025). Xenobiotic-induced liver injury: Molecular mechanisms and disease progression. Ecotoxicology and Environmental Safety, 303, 118854.
Yener, A. U., Sehitoglu, M. H., Ozkan, M. T. A., BEKLER, A., EKIN, A., Cokkalender, O. & KURT, T. (2015). Effects of kefir on ischemia-reperfusion injury. European Review for Medical & Pharmacological Sciences, 19(5).
Zhang, F., Xia, Y., Su, J., Quan, F., Zhou, H., Li, Q., ... & Jiang, Z. (2024). Neutrophil diversity and function in health and disease. Signal transduction and targeted therapy, 9(1), 343.
Zhao, H., Wu, L., Yan, G., Chen, Y., Zhou, M., Wu, Y., & Li, Y. (2021). Inflammation and tumor progression: signalling pathways and targeted intervention. Signal transduction and targeted therapy, 6(1), 263.
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