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In Vitro and in Vivo Therapeutic Potentials of 6-Gingerol in Combination With Amphotericin B for Treatment of Leishmania Major Infection: Powerful Synergistic and Multifunctional Effects Publisher Pubmed



Keyhani A1 ; Sharifi I1 ; Salarkia E1 ; Khosravi A1 ; Tavakoli Oliaee R1 ; Babaei Z1 ; Ghasemi Nejad Almani P1 ; Hassanzadeh S2 ; Kheirandish R2 ; Mostafavi M1 ; Hakimi Parizi M1 ; Alahdin S1 ; Sharifi F3 ; Dabiri S4 Show All Authors
Authors
  1. Keyhani A1
  2. Sharifi I1
  3. Salarkia E1
  4. Khosravi A1
  5. Tavakoli Oliaee R1
  6. Babaei Z1
  7. Ghasemi Nejad Almani P1
  8. Hassanzadeh S2
  9. Kheirandish R2
  10. Mostafavi M1
  11. Hakimi Parizi M1
  12. Alahdin S1
  13. Sharifi F3
  14. Dabiri S4
  15. Shamsi Meymandi S5
  16. Khamesipour A6
  17. Jafarzadeh A7
  18. Bamorovat M1
Show Affiliations
Authors Affiliations
  1. 1. Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran
  2. 2. Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
  3. 3. Research Center for Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran
  4. 4. Department of Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran
  5. 5. Department of Dermatology, Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran
  6. 6. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran

Source: International Immunopharmacology Published:2021


Abstract

The ongoing conventional drugs for leishmaniasis treatment are insufficient. The present study aimed to assess 6-gingerol alone and in combination with amphotericin B on Leishmania major stages using experimental and in vivo murine models. Here, arrays of experimental approaches were designed to monitor and evaluate the 6-gingerol potential therapeutic outcomes. The binding affinity of 6-gingerol and IFN-γ was the basis for docking conformations. 6-Gingerol combined with amphotericin B represented a safe mixture, extremely leishmanicidal, a potent antioxidant, induced a remarkable apoptotic index, significantly increased the expression of the Th1-related cytokines (IL-12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (STAT1, c-Fos, and Elk-1). In contrast, the expression of the Th2-related cytokines was significantly downregulated (p < 0.001). This combination was also potent when the lesion appearance was evaluated following three weeks of treatment. The histopathological and immunohistochemical patterns of the murine model represented clusters of CD4+ and CD8+ T lymphocytes which compressed and deteriorated the macrophages harboring Leishman bodies. The primary mode of action of 6-gingerol and amphotericin B involved broad mechanistic insights providing a coherent basis for further clinical study as a potential drug candidate for CL. In conclusion, 6-gingerol with amphotericin B synergistically exerted anti-leishmanial activity in vitro and in vivo and potentiated macrophages' leishmanicidal activity, modulated Th1- and Th2-related phenotypes improved the histopathological changes in the BALB/c mice infected with L. major. They elevated the leukocyte infiltration into the lesions. Therefore, this combination should be considered for treating volunteer patients with CL in clinical studies. © 2021 Elsevier B.V.
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