ABSTRACT
INTRODUCTION: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. OBJECTIVES: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. METHODS: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. RESULTS: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/ß-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/ß-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. CONCLUSION: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/ß-catenin signalling pathways.
ABSTRACT
A new guaiane-type sesquiterpenoid ethoxyvalerianol (1) and one known sesquiterpenoid valeranone (2) together with selina-4,7(11)-diene (3) and selinene (4), which were obtained from (+)-maaliol (5) by decyclization and dehydration, were isolated from Valeriana tangutica. Their structures were elucidated by 1D- and 2D-NMR spectroscopic data and HR-ESI-MS analysis.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Plants, Medicinal/chemistry , Pseudomonas aeruginosa/drug effects , Sesquiterpenes/isolation & purification , Valerian/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
Two new diarylheptanoids, juglanin A (1) and B (2), together with 15 known compounds, were isolated from the extract of the seed husks of walnuts (Juglans regia L.). The structures of 1 and 2 were elucidated by various spectroscopic methods including intensive 2D-NMR techniques, HR-ESI-MS, and X-ray single-crystal diffraction analysis, and the cytotoxic activities of 1, 2, and 10 against human hepatoma (Hep G2) cells was reported.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Diarylheptanoids/isolation & purification , Juglans/chemistry , Cell Line, Tumor , Diarylheptanoids/chemistry , Fruit/chemistry , Humans , Molecular ConformationABSTRACT
OBJECTIVE: To study the chemical constituents of Ligularia intermedia of Shanxi. METHOD: The compounds were isolated by column chromatography on silica gel and preparative TLC. The structures were identified by IR, MS, 1D/2DNMR spectral data and X-ray single crystal diffraction and other methods1. RESULT: Nine compound were isolated and identified as 8beta-hydroxyeremophil-7(11)-ene-12, 8alpha(4beta, 6alpha)-diolide (1), 8beta-methoxyeremophil-7(11)-ene-12, 8alpha(4beta, 6alpha)-diolide (2), petasin (3), isopetasin (4), liguhodgsonal (5), ligudentatol (6), ligujapone (7), lupeol (8) and lupeol palmitate (9). CONCLUSION: Compounds 2, 3, 4, 6, 7 and 9 were isolated from the plant for the first time.
Subject(s)
Asteraceae/chemistry , Plants, Medicinal/chemistry , Sesquiterpenes/isolation & purification , Molecular Conformation , Molecular Structure , Sesquiterpenes/chemistry , StereoisomerismABSTRACT
Five new eremophilenolides, 1beta-angeloyloxy-6beta,10beta-dihydroxy-8beta-methoxyeremophil-7(11)-en-8alpha,12-olide ( 1), 1beta-angeloyloxy-6beta,10alpha-dihydroxy-8alpha-methoxyeremophil-7(11)-en-8beta,12-olide ( 2), 1beta,6beta-diangeloyloxy-8beta,10beta-dihydroxyeremophil-(11)-en-8alpha,12-olide ( 3), 1beta,6beta-diangeloyloxy-8alpha,10 alpha-dihydroxyeremophil-7(11)-en-8beta,12-olide ( 4), 1beta-angeloyloxy-8-oxoeremophil-6,9-dien-12-oic acid methyl ester ( 5) and one known compound, 8beta,10beta-dihydroxyeremophilenolide ( 6) were isolated from the extract of the whole plant of Ligularia myriocephala Ling. Their structures and stereochemistry were elucidated by various spectroscopic methods including intensive 2D-NMR techniques (COSY, gHMQC, gHMBC and (1)H- (1)H NOESY) and HR-ESI-MS. A single-crystal X-ray experiment was performed for compound 1.