1. Academic Validation
  2. Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy

Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy

  • Biomed Pharmacother. 2016 Apr;79:129-34. doi: 10.1016/j.biopha.2016.01.041.
Lorena A Pinto 1 Cássio S Meira 1 Cristiane F Villarreal 2 Marcos A Vannier-Santos 1 Claudia V C de Souza 3 Ivone M Ribeiro 3 Therezinha C B Tomassini 3 Bernardo Galvão-Castro 4 Milena B P Soares 5 Maria F R Grassi 6
Affiliations

Affiliations

  • 1 Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil.
  • 2 Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Federal University of Bahia, Salvador, Bahia, Brazil.
  • 3 Farmanguinhos, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil.
  • 4 Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil.
  • 5 Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Center of Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Bahia, Brazil.
  • 6 Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil. Electronic address: grassi@bahia.fiocruz.br.
Abstract

Human T-lymphotropic virus type 1 (HTLV-1) induces a strong activation of the immune system, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Physalin F is a secosteroid with potent anti-inflammatory and immunomodulatory activities. The present study aimed to investigate the effects of physalin F on peripheral blood mononuclear cells (PBMC) of HAM/TSP subjects. A concentration-dependent inhibition of spontaneous proliferation of PBMC from HAM/TSP subjects was observed in the presence of physalin F, as evaluated by (3)H-thymidine uptake. The IC50 for physalin F was 0.97 ± 0.11 μM. Flow cytometry analysis using Cytometric Bead Array (CBA) showed that physalin F (10 μM) significantly reduced the levels of IL-2, IL-6, IL-10, TNF-α and IFN-γ, but not IL-17A, in supernatants of PBMC cultures. Next, Apoptosis induction was addressed by using flow cytometry to evaluate annexin V expression. Treatment with physalin F (10 μM) increased the apoptotic population of PBMC in HAM/TSP subjects. Transmission electron microscopy analysis of PBMC showed that physalin F induced ultrastructural changes, such as pyknotic nuclei, damaged mitochondria, enhanced autophagic vacuole formation, and the presence of myelin-like figures. In conclusion, physalin F induces Apoptosis of PBMC, decreasing the spontaneous proliferation and cytokine production caused by HTLV-1 Infection.

Keywords

Apoptosis; HTLV-1; Immunosuppressive activity; PBMC; Physalin F.

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