ABSTRACT
Cisplatin is a main compound for human hepatocellular carcinoma (HCC) chemotherapies, but it has certain cytotoxicity during applications. To release that, combining with other drugs are being as a regular plan in clinic. In our present study, we are focusing on one of active monomers extracted from Anemone Raddeana Regel, Raddeanin A (RA), which is on behalf of the same character like cisplatin in the tumor remedies. In order to investigate whether combination usage of RA and cisplatin can be priority to the later drug's effect development and its toxicity reduction in HCC, both of two drugs were treated 24 h or 48 h in QGY-7703 cells for estimating their abilities in tumor cell proliferation inhibition. Results show RA makes synergistic functions with cisplatin after measuring and analyzing their combination index (CI) values. Meanwhile it can strengthen cisplatin's effect through arresting the tumor cells in G0/G1 cycle and further promoting their apoptosis. Interestingly, the molecule signals correlated to tumor cell apoptosis containing both of p53 and bax are simultaneously activated, but bcl-2 and survivin are all depressed in mRNA level. Meanwhile, combining usage with RA can even raise the intracellular productions of reactive oxygen species (ROS). All these consequences reflect RA plays an important role in enhancing the therapeutic effect of cisplatin in HCC. This finding may guide for the drug usage of cisplatin in clinic practice.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cisplatin/pharmacology , Liver Neoplasms/drug therapy , Saponins/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Gene Expression Regulation, Neoplastic/drug effects , Humans , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Reactive Oxygen Species/metabolismABSTRACT
Background: Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Methods: Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3ß in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3ß, ß-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. Results: We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3ß by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3ß, and ß-catenin in the medial prefrontal cortex. Conclusion: Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.
Subject(s)
Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Oligosaccharides/pharmacology , Prefrontal Cortex/drug effects , beta Catenin/metabolism , Animals , Depressive Disorder/drug therapy , Depressive Disorder/metabolism , Disease Models, Animal , Male , Morinda , Prefrontal Cortex/metabolism , Rats, Sprague-Dawley , Resilience, Psychological/drug effects , Stress, Psychological/drug therapy , Stress, Psychological/metabolismABSTRACT
One new oleane-type triterpene saponin, named lysimachiagenoside A and the known 21-O-angeloylbarringtogenol C were isolated from the aerial parts of Lysimachia foenum-graecum Hance. 21-O-angeloylbarringtogenol C was a new natural product. These structures were identified on the basis of 1D- and 2D-NMR techniques, including 1H-1H COSY, HMQC, HMBC, TOCSY, and ROESY experiments as well as chemical methods.
Subject(s)
Drugs, Chinese Herbal/isolation & purification , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/isolation & purification , Primulaceae/chemistry , Saponins/isolation & purification , Triterpenes/isolation & purification , Drugs, Chinese Herbal/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oleanolic Acid/chemistry , Saponins/chemistry , Triterpenes/chemistryABSTRACT
Two new oleanane-type triterpene saponins, lysimachiagenoside C (1) and lysimachiagenoside D (2), were isolated from the aerial parts of Lysimachia foenum-graecum Hance. The structures were elucidated on the basis of 1D and 2D NMR techniques, including (1)H-(1)H COSY, HMQC, HMBC, TOCSY, and ROESY experiments as well as chemical methods.
Subject(s)
Drugs, Chinese Herbal/isolation & purification , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/isolation & purification , Primulaceae/chemistry , Saponins/isolation & purification , Drugs, Chinese Herbal/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oleanolic Acid/chemistry , Saponins/chemistryABSTRACT
The aim of the study was to look for the chemical constituents of the herb of Lysimachia foenum-graecum. The herb of Lysimachia foenum-graecum was extracted with 70% EtOH. The isolation and purification was performed with a combination of multi-column chromatography and the structure was determined by spectral analysis. The flavonoid compound was obtained and elucidated as kaempferol-7-O(4"-(E)-p-coumaroyl-)-alpha-L-rhmanopyranosyl)-3-O-beta-D-glucopyranosyl (1-->4)-alpha-L-rhmanopyranosyl (1-->2)-beta-D-glucopyranoside. It is a new flavonoid compound.
Subject(s)
Flavonoids/isolation & purification , Glucosides/isolation & purification , Primulaceae/chemistry , Flavonoids/chemistry , Glucosides/chemistry , Molecular Conformation , Molecular Structure , Plant Components, Aerial/chemistry , Plants, Medicinal/chemistryABSTRACT
OBJECTIVE: To investigate various activities of dissolved matter of glycyrrhizic acid of Radix Glycyrrhizae and the powder by supermicro-pulverization. METHOD: The contents of glycyrrhizic acid in different samples were tested. RESULT: The dissolved matter of glycyrrhizic acid was greatly increased by supermicro-pulverization. The more time used for grinding, the smaller the size of the powder, and the easier the glycyrrhizic acid would be dissolved. CONCLUSION: Supermicro-pulverization is helpful to the dissolved matter of glycyrrhizic acid of Radix Glycyrrhizae, and the size of powder exerts great influence on dissolved matter of glycyrrhizic acid.