ABSTRACT
Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.
Subject(s)
Anti-Inflammatory Agents , Cirsium , Esters , Lipopolysaccharides , Nitric Oxide , Triterpenes , Animals , Mice , Cirsium/chemistry , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Molecular Structure , Nitric Oxide/biosynthesis , Nitric Oxide/antagonists & inhibitors , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Lipopolysaccharides/pharmacology , Esters/pharmacology , Esters/chemistry , Macrophages/drug effectsABSTRACT
Five unusual seco-nortriterpenoids, 3ß-hydroxy-20,21-seco-30-nortaraxastan-20,21-dioic acid (1), 3ß-hydroxy-20,21-seco-30-nortaraxastan-20-oic-21-oate (2), 3ß-hydroxy-20-oxo-21,22-seco-30-nortaraxastan-22-oic acid (3), 3ß-hydroxy-19-oxo-20,21-seco-29,30-nortaraxastan-21-oic acid (4) and 3ß-hydroxy-19-oxo-20,21-seco-19-norlupan-21-oic acid (5) were isolated and elucidated from the anti-inflammatory activity fraction of the ethanol extract of Cirsium setosum. The structures of these compounds were established through spectroscopic methods. Preliminary biological assays showed that compounds 1-5 had significant inhibitory effect on NO production on lipopolysaccharide-stimulated RAW 264.7 cells, and compound 1 showed the strongest anti-inflammatory activity. This type of ring-opening compound is the first seco-triterpenoid structure discovered from the genus of Cirsium.
Subject(s)
Anti-Inflammatory Agents , Cirsium , Nitric Oxide , Phytochemicals , Triterpenes , RAW 264.7 Cells , Animals , Mice , Cirsium/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Molecular Structure , Triterpenes/pharmacology , Triterpenes/isolation & purification , Triterpenes/chemistry , Nitric Oxide/metabolism , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/chemistryABSTRACT
PURPOSE: The purpose of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of CYP17A1, CYB5A and the efficacy of abiraterone acetate treatment in patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Data were collected from 58 CRPC patients who had been treated with abiraterone acetate/prednisone (AA/P). The SNPs rs743572 and rs10883783 on CYP17A1 and SNPs rs1790834 and rs1790858 on CYB5A were assayed, and their relationship with prostate-specific antigen (PSA) response in patients after AA/P treatment, overall survival (OS) and progression-free survival (PFS) were analyzed by logistic regression, Cox regression, Kaplan-Meier and Log rank analyses. RESULTS: The SNP rs1790834 on CYB5A showed significant association with PSA response in CRPC patients treated with AA/P (P < 0.05), but rs743572, rs10883783 and rs1790858 did not. The rs1790834 variant significantly decreased both PFS and OS (P < 0.05). CONCLUSION: The CYB5A rs790834 genotype is a novel SNP related to CRPC and may be used as a biomarker for CRPC treatment.