Search

Abstract: Ethnopharmacological relevance: Ginsenoside Rg1, ginsenoside Rb1 and schizandrin are main bioactive components from Panax ginseng and Schisandra chinensis. They have been found in many prescriptions of Traditional Chinese Medicines (TCM) and proven to be effective for prevention and treatment of cardiovascular disease. It is valuable to investigate their pharmacokinetic and pharmacodynamic behavior and potential synergistic effect for better drug development and clinical application. Materials and methods: Pharmacokinetic and nitric oxide (NO) release pharmacodynamic drug–drug interactions of ginsenoside Rg1, ginsenoside Rb1 and schisandrin were studied after intravenous administration of each compound with the dose of 10mg/kg and their mixture with the total dose of 10mg/kg to isoproterenol (ISO)-induced myocardial ischemia rats. Drug concentrations in serum were determined using LC–MS method. Nitrite and nitrate ( ), the predominant oxidation product of NO in serum was used as an effective marker and quantitated by the method of high-performance liquid chromatography coupled with fluorescence detection (HPLC-FL). The main pharmacokinetic parameters of T 1/2β , MRT 0−∞, V d, Cl, and AUC, and the main pharmacodynamic parameters of C max, T max and AUEC were calculated by non-compartment model. Results: The results indicated ginsenoside Rb1 and (or) schisandrin in mixture could significantly postpone the elimination of ginsenoside Rg1 in rat serum. Co-administration of three compounds markedly increased the systemic exposure level of each compound in vivo. Ginsenoside Rg1 and ginsenoside Rb1 had the effect of inducing real-time NO release in rats concentration dependently. Schisandrin had no effect of inducing real-time NO release in this study. The mixture of ginsenoside Rg1, Rb1 and schisandrin administration exhibited synergistic effect of inducing NO release in ISO treated rats. Conclusions: The result obtained from this study suggested pharmacokinetic and pharmacodynamic drug–drug interactions between ginsenoside Rg1, Rb1 and schisandrin. The study provided valuable information for drug development and clinical application of TCM. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Ginsenoside Rg1, ginsenoside Rb1 and schizandrin are main bioactive components from Panax ginseng and Schisandra chinensis. They have been found in many prescriptions of Traditional Chinese Medicines (TCM) and proven to be effective for prevention and treatment of cardiovascular disease. It is valuable to investigate their pharmacokinetic and pharmacodynamic behavior and potential synergistic effect for better drug development and clinical application. Materials and methods: Pharmacokinetic and nitric oxide (NO) release pharmacodynamic drug–drug interactions of ginsenoside Rg1, ginsenoside Rb1 and schisandrin were studied after intravenous administration of each compound with the dose of 10mg/kg and their mixture with the total dose of 10mg/kg to isoproterenol (ISO)-induced myocardial ischemia rats. Drug concentrations in serum were determined using LC–MS method. Nitrite and nitrate ( ), the predominant oxidation product of NO in serum was used as an effective marker and quantitated by the method of high-performance liquid chromatography coupled with fluorescence detection (HPLC-FL). The main pharmacokinetic parameters of T 1/2β , MRT 0−∞, V d, Cl, and AUC, and the main pharmacodynamic parameters of C max, T max and AUEC were calculated by non-compartment model. Results: The results indicated ginsenoside Rb1 and (or) schisandrin in mixture could significantly postpone the elimination of ginsenoside Rg1 in rat serum. Co-administration of three compounds markedly increased the systemic exposure level of each compound in vivo. Ginsenoside Rg1 and ginsenoside Rb1 had the effect of inducing real-time NO release in rats concentration dependently. Schisandrin had no effect of inducing real-time NO release in this study. The mixture of ginsenoside Rg1, Rb1 and schisandrin administration exhibited synergistic effect of inducing NO release in ISO treated rats. Conclusions: The result obtained from this study suggested pharmacokinetic and pharmacodynamic drug–drug interactions between ginsenoside Rg1, Rb1 and schisandrin. The study provided valuable information for drug development and clinical application of TCM. [Copyright &y& Elsevier]

Abstract Ethnopharmacological relevance In traditional Chinese medicine (TCM), honey has been used as an additive in the heat-processing of herbal medicines to enhance their immunostimulatory activities. Aim of the study We investigated the immunostimulatory activity of heated honey in vitro and in vivo. Materials and methods For the in vitro study, we compared the differences among the inducible effects of honey subjected to various heating conditions on granulocyte colony-stimulating factor (G-CSF) secretion from the cultured enterocytes and investigated the active ingredient. For the in vivo study, we conducted a survival test of mice infected by Streptococcus pyogenes with and without oral administration of heated honey. Results We found that heating the honey induced the appearance of G-CSF secretions from the cultured enterocytes, and that this appearance depended on the heating temperature and time. No G-CSF secretions appeared when honey was not heated. Mice infected with Streptococcus pyogenes that were fed heated honey revealed prolonged survival. The active ingredient in heated honey was a high-molecular compound with about 730 kDa. When this compound was hydrolyzed, galactose, glucose, rhamnose, α -ribofuranose β -ribofuranose 1,5′:1′,5-dianhydride, and 5-hydroxymethylfurfural were generated. Conclusions Heated honey reveals immunostimulatory activity both in vitro and in vivo. These results support the scientific evidences of the TCM theory. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Licorice (the roots and rhizomes of Glycyrrhiza uralensis Fisch.) is occasionally used as crude drug following processing including roasting or honey-roasting (soaking with honey before roasting) in traditional Japanese Kampo medicine and traditional Chinese medicine (TCM). Aim of the study We investigated the differences in the inducible effect of processed licorice products on granulocyte colony-stimulating factor (G-CSF) secretion in cultured intestinal epithelial cells and elucidated the active ingredients in both unprocessed and processed licorice products. Materials and methods We prepared heat-processed licorice with or without pretreatment with honey, and fractionated the extracts by Sephadex G-100. Enterocyte-like differentiated MCE301 cells were incubated in media comprising a hot water extract of licorice products for 24 h, and the concentrations of G-CSF in the media were measured using enzyme-linked immunosorbent assay (ELISA). Results Licorice extract induced G-CSF secretion in MCE301 cells, and the active ingredients of licorice were high molecular compounds. Although the roasted licorice extract exhibited the activity similar to that of the unprocessed licorice extract, honey-roasted licorice extracts exhibited a significantly higher inducible effect on G-CSF secretion in the cells than that of unprocessed or roasted licorice extracts without pretreatment with honey. This enhanced activity was dependent on the temperature and heating time. Conclusions The enhanced inducible effect of honey-roasted licorice on G-CSF secretion might be attributed to the combined effect of licorice-derived high molecular compounds and heated-honey-derived compounds. The results of this study can scientifically explain the objective of processing via honey-roasting in TCM theory. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Magnesium lithospermate B (MLB), an active polyphenol acid of Radix Salviae Miltiorrhizae (Danshen), showed a wide range of pharmacological activities in cardiovascular diseases. However, its role in protection against ischemia/reperfusion injury in H9c2 cardiomyocytes has not been elucidated. This study was aimed to investigate the protective effect and potential molecular mechanisms of MLB on apoptosis in H9c2 cardiomyocytes in vitro. Materials and methods: We tested cell viability, shortening amplitude, necrosis, apoptosis, and the expression levels of Akt, phosphorylated Akt, Bcl-2 and Bax after 2-h simulated ischemia and 24-h simulated reperfusion in H9c2 cardiomyocytes. We further observed the contractile function in hearts after they were subjected to global 30-min ischemia and 180-min reperfusion. Results: Pretreatment with MLB markedly increased cell viability and while reducing evidence of necrosis and apoptosis in H9c2 cardiomyocytes. In addition, the expression of Bcl-2 and Bax protein was modulated. The results also showed that MLB significantly increased phosphorylation of Akt and that this phosphorylation can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor. Furthermore, MLB improved MI/R-induced myocardial contractile function. Conclusion: Our results showed that MLB prevents I/R-induced myocardial damage by reducing necrosis and apoptosis in H9c2 cardiomyocytes and improving myocardial function in rat hearts. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The aim of this study was to determine the anti-hepatitis B effect of isochlorogenic acid A isolated from Laggera alata (Asteraceae), a traditional Chinese herbal medicine. Materials and methods: The anti-hepatitis B activity of isochlorogenic acid A was evaluated by the d-galactosamine (D-GalN)-induced HL-7702 hepatocyte damage model and the HBV-transfected HepG2.2.15 cells. Results: Isochlorogenic acid A significantly improved HL-7702 hepatocyte viability and markedly inhibited the productions of HBsAg and HBeAg. The inhibitory rates of isochlorogenic acid A on the HBsAg and HBeAg expressions were 86.9% and 72.9%, respectively. In addition, isochlorogenic acid A declined markedly the content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) and induced significantly the heme oxygenase-1 (HO-1) expression in HepG2.2.15 cells. Conclusions: Isochlorogenic acid A was verified to possess the potent anti-hepatitis B activity. The anti-HBV target of isochlorogenic acid A is probably associated with blocking the translation step of the HBV replication. Overexpression of HO-1 may contribute to the anti-HBV activity of isochlorogenic acid A by reducing the stability of the HBV core protein and thus blocking the refill of nuclear HBV cccDNA. Additionally, the hepatoprotective effect of isochlorogenic acid A could be achieved by its antioxidative property and induction of HO-1. [Copyright &y& Elsevier]

This study addresses the rapid discovery of the active compounds (the original constituents and/or metabolites) of a traditional Chinese drug, Smilacis Glabrae Rhizoma (SGR). The aim of this study was to develop a new method to find out the active compounds of traditional drugs in vivo. A method was established to discover and identify the potential active compounds in drug-containing plasma from rats that were orally administered SGR extract, utilizing the relationship between the individual differences in blood drug concentrations in the rats and the resulting differences in pharmacological effect, and the method was denoted as the RID-PE method. For this method, we used high-performance liquid chromatography with a diode array detector combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (LC-MSn) to identify the compounds (the original constituents and metabolites) and to determine the peak areas of the compounds in drug-containing plasma following SGR treatment. The anti-inflammatory effect of SGR was evaluated using a carrageenan-induced inflammatory rat model. According to the percent inhibition of paw edema in each model rat (14 rats total) orally administered SGR extract, the plasma samples from the rats were sorted and divided into 7 groups. Each group consisted of two plasma samples, and their percent inhibition of paw edema were similar to each other. We performed an LC-MSn analysis on 3 plasma groups, which showed large differences in the inhibition rates, with percent inhibitions of 92.7%, 72.4% and 38.4%. The correlation coefficients (r) between the peak area of each compound and the pharmacological effect (inhibition ratio) of SGR in the three groups were analyzed using SPSS software. When the correlation coefficients of the compounds are greater than 0.8 (0.8 < r ≤1), these compounds are strongly and positively correlated with anti-inflammatory activity, making them potential anti-inflammatory active compounds. Fifty-eight potential anti-inflammatory compounds (0.8 < r ≤ 1) from SGR were discovered in model rat plasma using the RID-PE method, 47 of which were considered to be new potentially anti-inflammatory compounds. Among these compounds, four original constituents and 5 isomers of potential anti-inflammatory metabolites were validated to have significant anti-inflammatory effects, and they included astilbin, syringic acid, catechin, coumalic acid, resveratrol-3′-O-glucuronide (RG, isomer of M2 or M3), 3′-O-methyl-(+)-epicatechin-4′-O-glucuronide (CA-1, isomer of M16), 4′-O-methyl-(+)-epicatechin-3′-O-glucuronide (CA-2, isomer of M16), 4′-O-methyl-(+)-epicatechin-7-O-glucuronide (CA-3, isomer of M16) and 3′-O-methyl-(+)-epicatechin-7-O-glucuronide (CA-4, isomer of M16). In addition, four isomers (CA-1—CA-4) were reported to have anti-inflammatory effects for the first time, and CA-3 was a new compound. The RID-PE method can be used to discover and identify the active constituents and metabolites of SGR systematically and in vivo. Furthermore, these findings enhance our understanding of the metabolism and effective forms of SGR. Image 1 [ABSTRACT FROM AUTHOR]