Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion

by Selleckchem | Dec 18 2023

Context: The alkaloids of Narcissus tazetta L. var. Chinensis Roem (Amaryllidaceae) have antitumor and antiviral activities. However, the immunopharmacological effects of one of its constituents, pseudolycorine chloride (PLY), have not been reported yet.

Objective: We evaluated the effect of PLY on myeloid-derived suppressor cells (MDSCs) expansion and differentiation into monocyte-like MDSCs (M-MDSCs) and examined whether PLY alleviates Th17 cell-mediated experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).

Materials and methods: In vitro, MDSCs were treated with PLY (0.67, 2 and 6 μM) or solcitinib (10 μM, positive control) for 48 or 96 h, and their proliferation, expansion, and differentiation into M-MDSCs were examined by flow cytometry. Myelin oligodendrocyte glycoprotein (MOG35-55) was used to induce EAE in female C57BL/6 mice, and the mice were treated with 40 mg/kg/d PLY or 1 mg/kg/d FK-506 (tacrolimus, positive control) for 21 days. Inflammatory infiltration, spinal cord demyelination, and MDSCs and Th17 cells infiltration into the spinal cord were examined using haematoxylin and eosin staining, Luxol fast blue staining, and immunofluorescence, respectively.

Results: In vitro, PLY (IC50/24 h = 6.18 μM) significantly inhibited IL-6 and GM-CSF-induced MDSCs proliferation, expansion and differentiation into M-MDSCs at all concentrations used. However, these concentrations did not show cytotoxicity. In mice, PLY (40 mg/kg) treatment alleviated EAE and inhibited inflammatory infiltration, demyelination, and MDSCs and Th17 cells infiltration into the spinal cord.

Discussion and conclusions: PLY may be an excellent candidate for the treatment of MS and other autoimmune diseases.

Comments:

The study described in the provided context investigates the immunopharmacological effects of pseudolycorine chloride (PLY), a constituent of Narcissus tazetta L. var. Chinensis Roem, on myeloid-derived suppressor cells (MDSCs) and experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).

The researchers aimed to evaluate how PLY affects the expansion and differentiation of MDSCs into monocyte-like MDSCs (M-MDSCs). In the in vitro experiments, MDSCs were treated with different concentrations of PLY, and the effects on proliferation, expansion, and differentiation were examined. The results showed that PLY effectively inhibited MDSCs proliferation, expansion, and differentiation into M-MDSCs without causing cytotoxicity.

Furthermore, the researchers used a murine model of MS induced by myelin oligodendrocyte glycoprotein (MOG35-55) and treated the mice with PLY. The treatment with PLY significantly alleviated EAE symptoms and reduced inflammatory infiltration, spinal cord demyelination, as well as MDSCs and Th17 cells infiltration into the spinal cord.

Based on these findings, the study suggests that PLY could be a promising candidate for the treatment of MS and other autoimmune diseases. Its ability to modulate MDSCs and inhibit Th17 cell-mediated inflammation in the EAE model highlights its potential immunomodulatory effects, making it a subject of interest for further research and development in the field of autoimmune disease therapies.