ABSTRACT
OBJECTIVE: To explore the molecular mechanism of 17-AAG in the treatment of systemic lupus erythematosus (SLE), and the effects of the heat shock protein 90 (HSP90) inhibitor 17-AAG on the activation and proliferation of lymphocytes and the AKT/GSK3ß signaling pathway in MRL/lpr mice were detected. METHODS: MRL/lpr mice were randomly divided into the control group and the experimental group. The experimental group was injected intraperitoneally with 17-AAG, and T lymphocytes were separated by magnetic beads. Lymphocyte proliferation was detected by MTT and flow cytometry (FCM), and the expression of the HSP90 protein and PI3K/AKT signaling pathway-related proteins was detected by Western blotting. Renal histopathology and immune complex deposition were also observed in both groups. RESULTS: Immune complex deposition and inflammation decreased in kidneys from MRL/lpr mice in the experimental group. HSP90 protein expression, T lymphocyte proliferation and phosphorylated AKT and GSK3ß levels also decreased in the experimental group. CONCLUSION: 17-AAG can inhibit the activation and proliferation of T lymphocytes and downregulate the AKT/GSK3ß signaling pathway, which may be relevant for the treatment of SLE.
Subject(s)
Benzoquinones/pharmacology , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Lactams, Macrocyclic/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , T-Lymphocytes/drug effects , Animals , Benzoquinones/chemistry , Cell Proliferation/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Glycogen Synthase Kinase 3 beta/metabolism , HSP90 Heat-Shock Proteins/metabolism , Lactams, Macrocyclic/chemistry , Mice , Mice, Inbred MRL lpr , Molecular Structure , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Structure-Activity Relationship , T-Lymphocytes/immunologyABSTRACT
Three new triterpenoid saponins, tomentoside A (1), B (2) and C (3), along with four known saponins (4-7) were isolated from the root of Anemone tomentosa. The structures of the new compounds were elucidated as 3-O-ß-D-ribopyranosyl-(1â3)-α-L-rhamnopyranosyl-(1â2)-[ß-D-glucopyranosyl-(1â4)]-α-L-arabinopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside (1), 3-O-ß-D-ribopyranosyl-(1â3)-α-L-rhamnopyranosyl-(1â2)-[ß-D-glucopyranosyl-(1â4)]-ß-D-xylopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside (2) and 3-O-ß-D-galactopyranosyl-(1â3)-α-L-rhamnopyranosyl-(1â2)-ß-D-xylopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside (3) on the basis of chemical and spectral evidence. In the oligosaccharide chains of compound 3, the characteristic D-galactose residue is a rare structural feature and secondly encountered among triterpenoid saponins from Anemone.
