Effects of polymethoxyflavonoids on T helper 17 cell differentiation in vitro and in vivo.

We examined the effects of polymethoxyflavonoids (PMFs) on T helper (Th) 17 cell differentiation in vitro and in vivo. Five different PMFs including nobiletin (NOB), sudachitin (SUD), demethoxysudachitin, heptamethoxyflavone and natsudaidain were used for the in vitro study, and effects of those flavonoids on Th17 responses were investigated. NOB and heptamethoxyflavone significantly suppressed the proliferation response, but SUD, demethoxysudachitin and natsudaidain did not suppress the proliferation response. All of the five flavonoids decreased IL-17A production. Mice with experimentally induced autoimmune encephalomyelitis were used as an in vivo Th17 differentiation model. We focused on two flavonoids, NOB and SUD, and examined the effects of those flavonoids. NOB significantly suppressed Th17 cell proliferation and cytokine responses, but SUD only decreased proliferation responses. The results suggest that the suppressive effect of NOB on Th17 response in vivo is stronger than that of SUD. J. Med. Invest. 70 : 166-170, February, 2023.

Essential Oil of Citrus sudachi Suppresses T Cell Activation Both In Vitro and In Vivo.

The essential oil of Citrus sudachi (sudachi oil) is extracted from the peel of sudachi, a citrus plant. We investigated the effect of sudachi oil on immune function in both in vitro antigen (Ag) induced lymphocyte activation and in vivo Ag-specific immune response. In the in vitro study, the proliferative activity of splenocytes upon Ag-specific and non-specific stimulation was suppressed by treatment with sudachi oil in a dose-dependent manner. In addition, the expression level of Ag-presentation-related molecules and their Ag-presenting function on dendritic cells were suppressed by sudachi oil. To examine how sudachi oil regulates an Ag-specific immune response in vivo, mice were immunized with ovalbumin and the immune response of the mice was investigated. Ag-specific proliferation response of splenocytes from mice treated with sudachi essential oil was significantly suppressed. The results indicate that sudachi oil suppresses T cell and dendritic cell functions in vitro and Ag-specific T cell induction in vivo.

Nobiletin suppresses the development of experimental autoimmune encephalomyelitis mediated by modulation of T helper 17 cell differentiation.

Multiple sclerosis is an organ-specific autoimmune disease that targets the myelin antigen in the central nervous system. Nobiletin is a dietary polymethoxylated flavonoid found in citrus fruits. In this study, we investigated how nobiletin affects the disease state and immune responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis mice. Nobiletin was administered orally from 14 days before immunization until the end of the experiment, and clinical scores were determined. The production levels of interleukin-17A and interferon-γ were measured in a culture supernatant of splenocytes stimulated with myelin oligodendrocyte glycoprotein. In addition, flow cytometric analysis was performed to examine the effect of nobiletin on T cell differentiation in vitro. Admin-istration of nobiletin significantly decreased the clinical score and interleukin-17A production in splenocytes. Furthermore, in vitro analysis showed that nobiletin significantly suppressed Th17 cell differentiation and interleukin-17A production in a dose-dependent manner. The results suggest that nobiletin attenuates experimental autoimmune encephalomyelitis severity through modulation of Th17 cell differentiation.