ABSTRACT
Salvianolic acid A (Sal A), an important constituent of Radix Salviae Miltiorrhizae (RSM), is effective for the treatment of myocardial infarction (MI) and coronary heart disease due to its potential in the improvement of acute myocardial ischemia. However, its content is very low in RSM. So it is obvious to find a rich source of Sal A or to improve its content by conversion of other related components into Sal A modifying reaction conditions. In this research we focused on the conversion of Sal B into Sal A in aqueous solutions of RSM by using different reaction conditions including pH, temperature, pressure and humidity. During the reactions, the contents of Sal A, Sal B and danshensu in the RSM were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LCMS). The results indicated that the conversion of Sal B into Sal A in RSM tissues under the conditions of a high temperature, high pressure and high humidity was efficient and thereby, was readily utilized to prepare rich Sal A materials in practice.
Subject(s)
Benzofurans/chemistry , Caffeic Acids/chemical synthesis , Drugs, Chinese Herbal/chemistry , Lactates/chemical synthesis , Salvia miltiorrhiza/chemistry , Caffeic Acids/therapeutic use , Chromatography, High Pressure Liquid , Hot Temperature , Humidity , Lactates/analysis , Lactates/therapeutic use , Mass Spectrometry , Myocardial Ischemia/drug therapy , Phytotherapy , Plant Roots , PressureABSTRACT
We have previously reported that the danshensu-cysteine conjugate N-((R)-3-benzylthio-1-methoxy-1-oxo-2-propanyl)-2-acetoxy-3-(3,4-diacetoxyphenyl) propanamide (DSC) is a potent anti-oxidative and anti-apoptotic agent. Herein, we further design and asymmetrically synthesize two diastereoisomers of DSC and explore their potential bioactivities. Our results show that DSC and its two diastereoisomers exert similar protective effects in hydrogen peroxide (H2O2)-induced cellular injury in SH-SY5Y cells, as evidenced by the increase of cell viability, superoxide dismutase (SOD), and reduced glutathione (GSH) activity, and glutathione peroxidase (GPx) expression, and the decrease of cellular morphological changes and nuclear condensation, lactate dehydrogenase (LDH) release, and malondialdehyde (MDA) production. In H2O2-stimulated human umbilical vein endothelial cells (HUVEC), DSC concentration-dependently attenuates H2O2-induced cell death, LDH release, mitochondrial membrane potential collapse, and modulates the expression of apoptosis-related proteins (Bcl-2, Bax, caspase-3, and caspase-9). Our results provide strong evidence that DSC and its two diastereoisomers have similar anti-oxidative activity and that DSC exerts significant vascular-protective effects, at least in part, through inhibition of apoptosis and modulation of endogenous antioxidant enzymes.
Subject(s)
Apoptosis/drug effects , Drugs, Chinese Herbal/chemistry , Endothelial Cells/drug effects , Protective Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Cysteine/chemical synthesis , Cysteine/chemistry , Cysteine/pharmacology , Drugs, Chinese Herbal/chemical synthesis , Drugs, Chinese Herbal/pharmacology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Glutathione Peroxidase/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Hydrogen Peroxide/metabolism , Lactates/chemical synthesis , Lactates/chemistry , Lactates/pharmacology , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Protective Agents/chemical synthesis , Protective Agents/pharmacologyABSTRACT
CONTEXT: The destabilization of ß-amyloid (Aß) peptide aggregates and the protection of functional cells are the attractive therapeutic strategies for Alzheimer's disease (AD). Some active ingredients of Salvia miltiorrhiza f. alba C.Y.Wu & H.W.Li (Lamiaceae) (SM) have attracted increasing attention for the treatment of neurodegenerative diseases. OBJECTIVE: Salvianic borneol ester (SBE) is a new compound based on SM formulas. The present study was designed to examine the anti-amyloid effects and neuroprotection of SBE in vitro. MATERIALS AND METHODS: The destabilizing effects of SBE and its related compounds (salvianic acid A and borneol) on preformed Aß oligomers were measured by using fluorescence spectroscopy with thioflavin T (ThT) and the destabilizing effects of SBE were further confirmed visually by transmission electron microscopy (TEM). The neuroprotective effects of SBE against hydrogen peroxide (H(2)O(2))-induced toxicity in human neuroblastoma cells (SH-SY5Y) and motor neuron hybridoma cells (VSC 4.1) were shown by MTT assay and morphological observation. RESULTS: SBE showed the most significant destabilizing effect, though the mixture of salvianic acid A and borneol also destabilized Aß1-40 oligomers. The destabilizing activity of salvianic acid A or borneol alone was not significant. SBE destabilized Aß1-40 oligomers in dose- and time-dependent manners and the destabilizing effect could also be seen in the photographs of TEM. Furthermore, SBE could protect SH-SY5Y cells and VSC 4.1 cells against H(2)O(2)-induced toxicity in a dose-dependent manner. DISCUSSION AND CONCLUSION: SBE had the bifunctional activities of anti-amyloid and neuroprotection. It may have therapeutic potential for AD and be an alternative lead compound for developing new drugs against AD.