Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme
African trypanosomiasis, a neglected tropical disease, is caused by diverse species of the protozoan parasite belonging to the genus Trypanosoma. Although anti-trypanosomal medications exist, the increase in drug resistance and persistent antigenic variation has necessitated the development of newer...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1275365/full |
| _version_ | 1797649435169128448 |
|---|---|
| author | Nnamdi Ikeogu Folayemi Olayinka-Adefemi Chidalu Edechi Chukwunonso Onyilagha Ping Jia Aaron Marshall Julius Ode Jude Uzonna |
| author_facet | Nnamdi Ikeogu Folayemi Olayinka-Adefemi Chidalu Edechi Chukwunonso Onyilagha Ping Jia Aaron Marshall Julius Ode Jude Uzonna |
| author_sort | Nnamdi Ikeogu |
| collection | DOAJ |
| description | African trypanosomiasis, a neglected tropical disease, is caused by diverse species of the protozoan parasite belonging to the genus Trypanosoma. Although anti-trypanosomal medications exist, the increase in drug resistance and persistent antigenic variation has necessitated the development of newer and more efficacious therapeutic agents which are selectively toxic to the parasite. In this study, we assessed the trypanocidal efficacy of Crosspteryx fibrifuga leaf extract (C.f/L-extract) in vitro. Following treatment of T. congolense parasites with C.f/L-extract, we observed a significant decrease in parasite number and an elevation in the expression of the apoptotic markers, Annexin V and 7-Aminoactinomycin D (7AAD). Interestingly, at the same concentration (50 μg/mL), C.f/L-extract was not cytotoxic to murine whole splenocytes. We also observed a significant increase in pro-inflammatory cytokines and nitric oxide secretion by bone marrow derived macrophages following treatment with C.f/L-extract (10 μg/mL and 50 μg/mL) compared to PBS treated controls, suggesting that the extract possesses an immune regulatory effect. Treatment of T. congolense infected mice with C.f/L-extract led to significant decrease in parasite numbers and a modest increase in mouse survival compared to PBS treated controls. In addition, there was a significant increase in CD4+IFN-γ+ T cells and a decrease in CD4+IL-10+ T cells in the spleens of T. congolense infected mice treated with C.f/L-extract. Interestingly, C.f/L-extract treatment decreased the activity of superoxide dismutase (an enzyme that protects unicellular organisms from oxidative stress) in T. congolense parasites but not in splenocytes. Collectively, our study has identified C.f/L-extract as a potential anti-trypanosomal agent that warrant further investigation and possibly explored as a treatment option for T. congolense infection. |
| first_indexed | 2024-03-11T15:46:05Z |
| format | Article |
| id | doaj.art-700a88ce6d5542ccaca497752f68f436 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-11T15:46:05Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-700a88ce6d5542ccaca497752f68f4362023-10-26T06:20:30ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-10-011410.3389/fmicb.2023.12753651275365Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzymeNnamdi Ikeogu0Folayemi Olayinka-Adefemi1Chidalu Edechi2Chukwunonso Onyilagha3Ping Jia4Aaron Marshall5Julius Ode6Jude Uzonna7Department of Immunology, University of Manitoba, Winnipeg, MB, CanadaDepartment of Immunology, University of Manitoba, Winnipeg, MB, CanadaDepartment of Pathology, University of Manitoba, Winnipeg, MB, CanadaNational Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, CanadaDepartment of Immunology, University of Manitoba, Winnipeg, MB, CanadaDepartment of Immunology, University of Manitoba, Winnipeg, MB, CanadaDepartment of Veterinary Pharmacology and Toxicology, University of Abuja, Abuja, NigeriaDepartment of Immunology, University of Manitoba, Winnipeg, MB, CanadaAfrican trypanosomiasis, a neglected tropical disease, is caused by diverse species of the protozoan parasite belonging to the genus Trypanosoma. Although anti-trypanosomal medications exist, the increase in drug resistance and persistent antigenic variation has necessitated the development of newer and more efficacious therapeutic agents which are selectively toxic to the parasite. In this study, we assessed the trypanocidal efficacy of Crosspteryx fibrifuga leaf extract (C.f/L-extract) in vitro. Following treatment of T. congolense parasites with C.f/L-extract, we observed a significant decrease in parasite number and an elevation in the expression of the apoptotic markers, Annexin V and 7-Aminoactinomycin D (7AAD). Interestingly, at the same concentration (50 μg/mL), C.f/L-extract was not cytotoxic to murine whole splenocytes. We also observed a significant increase in pro-inflammatory cytokines and nitric oxide secretion by bone marrow derived macrophages following treatment with C.f/L-extract (10 μg/mL and 50 μg/mL) compared to PBS treated controls, suggesting that the extract possesses an immune regulatory effect. Treatment of T. congolense infected mice with C.f/L-extract led to significant decrease in parasite numbers and a modest increase in mouse survival compared to PBS treated controls. In addition, there was a significant increase in CD4+IFN-γ+ T cells and a decrease in CD4+IL-10+ T cells in the spleens of T. congolense infected mice treated with C.f/L-extract. Interestingly, C.f/L-extract treatment decreased the activity of superoxide dismutase (an enzyme that protects unicellular organisms from oxidative stress) in T. congolense parasites but not in splenocytes. Collectively, our study has identified C.f/L-extract as a potential anti-trypanosomal agent that warrant further investigation and possibly explored as a treatment option for T. congolense infection.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1275365/fullCrosspteryx fibrifugaTrypanosoma. Congolensesuperoxide dismutaseinterferon-gammahost response |
| spellingShingle | Nnamdi Ikeogu Folayemi Olayinka-Adefemi Chidalu Edechi Chukwunonso Onyilagha Ping Jia Aaron Marshall Julius Ode Jude Uzonna Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme Frontiers in Microbiology Crosspteryx fibrifuga Trypanosoma. Congolense superoxide dismutase interferon-gamma host response |
| title | Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme |
| title_full | Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme |
| title_fullStr | Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme |
| title_full_unstemmed | Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme |
| title_short | Crosspteryx fibrifuga leaf extract enhances host resistance to Trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme |
| title_sort | crosspteryx fibrifuga leaf extract enhances host resistance to trypanosoma congolense infection in mice by regulating host immune response and disrupting the activity of parasite superoxide dismutase enzyme |
| topic | Crosspteryx fibrifuga Trypanosoma. Congolense superoxide dismutase interferon-gamma host response |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1275365/full |
| work_keys_str_mv | AT nnamdiikeogu crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT folayemiolayinkaadefemi crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT chidaluedechi crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT chukwunonsoonyilagha crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT pingjia crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT aaronmarshall crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT juliusode crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme AT judeuzonna crosspteryxfibrifugaleafextractenhanceshostresistancetotrypanosomacongolenseinfectioninmicebyregulatinghostimmuneresponseanddisruptingtheactivityofparasitesuperoxidedismutaseenzyme |