Immunomodulatory Properties of Terminalia brownii Fresen and Carissa edulis (Forssk.) Vahl Extracts

Abstract

Microbial infections are currently on the rise and this significantly increases the rates of mortality and cases of disability worldwide. This surge is attributed to the emergence of antimicrobial resistance, rendering antimicrobial drugs ineffective. Therefore, there is a critical need to develop alternative therapeutic agents with a different mechanism of action, including immunomodulation. Terminalia brownii and C. edulis are traditionally used to manage infectious diseases including sexually transmitted infections, hepatitis, tuberculosis, pneumonia, among others. However, their impact on the immune system remains unclear. Therefore, the present study investigated the effect of these plants on the immune system. Methanol and dichloromethane were used for the extraction of plant materials. Female Swiss albino mice and Wistar rats were used in this study. To determine the plant extracts’ effects on innate immune responses, leucocyte counts, and production of nitric oxide and tumour necrosis factor-alpha by murine macrophages were determined. The 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide assay was conducted to assess the viability of Vero cells treated with the plant extracts. To establish the plant extracts’ effects on cellular and humoral immune responses, levels of tumour necrosis factor-alpha, interferon-gamma, interleukin-2, interleukin-4, and interleukin-5 in mice serum were assessed, and the delayed-type hypersensitivity reaction and haemagglutination antibody titer assay were conducted. Phytochemical analysis was accomplished through gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. In addition, the safety of the plant extracts was assessed through acute and sub-acute toxicity studies. Administration of the plant extracts significantly (p < 0.05) augmented total and differential leukocyte counts in pyrogallol-treated mice in contrast with the control. The extracts did not have an effect on Vero cells’ viability at all tested concentrations. Furthermore, the extracts stimulated macrophages to produce significantly (p < 0.05) elevated levels of nitric oxide and tumour necrosis factor-alpha. The serum of extract-treated mice showed significantly (p < 0.05) increased levels of tumour necrosis factor-alpha, interferon-gamma, and interleukin-2 but significantly (p < 0.05) decreased levels of interleukin-4 and interleukin-5 compared to the serum of the control mice. The extracts were also found to significantly (p < 0.05) augment delayed-type hypersensitivity and antibody titers. Additionally, T. brownii and C. edulis exhibited synergism in both innate and adaptive immune responses. The extracts did not induce any acute or sub-acute toxicity in rats. The plant extracts were found to contain diverse compounds (phenols, triterpenoids, flavonoids, tannins, fatty acids, and steroids) with immunomodulatory properties. In conclusion, the modulatory effect on the immune system exhibited by the tested extracts was ascribed to the identified compounds. Additionally, the extracts were non-toxic. The findings of this study provide a crucial ethnopharmacological lead towards the development of novel immunomodulatory agents of herbal origin that can be used to manage microbial infections and immune-related disorders. Terminalia brownii and C. edulis methanol and dichloromethane extracts should therefore be considered as potential candidates for developing immunomodulatory herbal formulations.