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

• Published in: Biomedicine & pharmacotherapy 2016-04, Vol.79, p.129-134
• Main Authors: Pinto, Lorena A, Meira, Cássio S, Villarreal, Cristiane F, Vannier-Santos, Marcos A, de Souza, Claudia V.C, Ribeiro, Ivone M, Tomassini, Therezinha C.B, Galvão-Castro, Bernardo, Soares, Milena B.P, Grassi, Maria F.R
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Proliferation - drug effects; Cytokines - metabolism; HTLV-1; Humans; Immunosuppressive activity; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Internal Medicine; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - pathology; Leukocytes, Mononuclear - ultrastructure; Medical Education; Paraparesis, Tropical Spastic - blood; Paraparesis, Tropical Spastic - drug therapy; Paraparesis, Tropical Spastic - pathology; PBMC; Phosphatidylserines - metabolism; Physalin F; Physalis - chemistry; Secosteroids - chemistry; Secosteroids - pharmacology; Secosteroids - therapeutic use
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2016.01.041

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 by3 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.