Isogarcinol Is a New Immunosuppressant

Abstract

Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. In this study we used CN as a target enzyme to investigate the immunosuppressive properties of a series of natural compounds from Garcinia mangostana L., and discovered an active compound, isogarcinol. Enzymatic assays showed that isogarcinol inhibited CN in a dose-dependent manner. At concentrations resulting in relatively low cytotoxicity isogarcinol significantly inhibited proliferation of murine spleen T-lymphocytes induced by concanavalin A (ConA) and the mixed lymphocyte reaction (MLR). In addition, it performed much better in acute toxicity tests and via oral administration in mice than cyclosporin A (CsA), with few adverse reactions and low toxicity in experimental animals. Oral administration of isogarcinol in mice resulted in a dose-dependent decrease in delayed type hypersensitivity (DTH) and prolonged graft survival in allogeneic skin transplantation. These findings suggest that isogarcinol could serve as a new oral immunomodulatory drug for preventing transplant rejection, and for long-term medication in autoimmune diseases.

Isogarcinol Extracted from Garcinia mangostana L. Ameliorates Systemic Lupus Erythematosus-like Disease in a Murine Model

“…Isogarcinol exhibited a better viability of spleen cells, and the serum indices, such as glutamic-pyruvic transaminase, glytamicoxalacetic transaminease, total bilirubin, urea nitrogen, and creatinine, were abnormally high in the CsA group compared with the isogarcinol group. 19 Similar experiments regarding the toxicity of CsA were found in the collagen-induced arthritis mouse model. 37 These results all link with the severe hepatotoxicity and nephrotoxicity of CsA.…”

“…19,20 The inflammatory cytokines TNF-α, IL-1β, and IL-6 produced by macrophages play an essential role in responding to infection and inflammation. Moreover, the kidney mRNA levels of TNF-α and IL-1β as well as protein levels in lupus-prone MRL/lpr mice have been found to increase.…”

“…20 Furthermore, isogarcinol had lower toxicity on liver and kidney function than did CsA in experimental animals. 19,20 On the basis of our previous study, we hypothesized that isogarcinol can inhibit the stimulation of CD4 T cells and exhibit an anti-inflammatory effect in the cGVHD mouse model, and we aimed both to determine whether orally administered isogarcinol could be a novel and effective agent for the treatment of SLE and to elucidate the potential underlying mechanisms.…”

Prenylated Polyphenols from Clusiaceae and Calophyllaceae with Immunomodulatory Activity on Endothelial Cells

“…A number of them are prenylated compounds, which often contributes to increase their biological activities [17]. Several polyphenols isolated from these families exhibit anti-inflammatory [18] or immunosuppressive [19, 20] activities and some species are used in folk medicine against inflammatory diseases [21]. …”

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“…Cyclotides, ribosomally synthesized plant peptides have growth-inhibiting effects on primary cells of the human immune system 18 . The isogarcinol, active compound from Garcinia mangostana L. inhibite Calcineurin unique protein phosphatase, plays an important role in immune regulation in a dose-dependent manner 19 . Natural therapies help to regulate the immune system's aggressive behavior without suppressing necessary defenses 20 .…”