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Zhiqiang Liu - One of the best experts on this subject based on the ideXlab platform.
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metabolites and metabolic pathways of Mesaconitine in rat liver microsomal investigated by using uplc ms ms method in vitro
Acta pharmaceutica Sinica, 2013Co-Authors: Shu Liu, Fengrui Song, Ruixing Zhang, Zhiqiang LiuAbstract:Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of Mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 Mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of Mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of Mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of Mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of Mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes.
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intestinal transport of pure diester type alkaloids from an aconite extract across the caco 2 cell monolayer model
Planta Medica, 2012Co-Authors: Rong Tsao, Zhiqiang Liu, Zhigang Sui, Zhongying LiuAbstract:Aconitine (AC), Mesaconitine (MA), and hypaconitine (HA) are the active alkaloids identified in aconite tuber, an important traditional Chinese medicine. The study is aimed to investigate their intestinal transport profiles and potential interaction during the intestinal absorption using the Caco-2 cell monolayer model. All three alkaloids had good permeability with P-app values greater than 1 x 10(-6) cm.s(-1). However, AC, MA, and HA in a mixture and as an extract, in both cases with the same content of alkaloids, showed higher transport efficiency in the apical to basolateral, and lower transport efficiency in the basolateral to apical directions. Digoxin, as a P-glycoprotein (P-gp) substrate, was substantially effluxed in the basolateral to apical direction but inhibited by the three alkaloids. Furthermore, the backwards transport of MA and HA was inhibited by the P-gp inhibitor verapamil. These observations indicated that the three alkaloids may not only be P-gp inhibitors but also its substrates; they interact with each other and can potentially enhance their own bioavailability when taken concomitantly.
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exploring the ester exchange reactions of diester diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry
Rapid Communications in Mass Spectrometry, 2003Co-Authors: Yong Wang, Fengrui Song, Zhiqiang Liu, Lei Shi, Shuying LiuAbstract:The chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester-exchange reactions for aconitine-type diester-diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of Mesaconitine and hypaconitine standards with liquorice root. It was found that diester-diterpenoid aconitines were converted into lipo-alkaloids as well as monoester alkaloids by the decoction of aconite.
Yinghui Wei - One of the best experts on this subject based on the ideXlab platform.
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analysis on the metabolites of Mesaconitine in the rat urine by liquid chromatography and electrospray ionization mass spectrometry
Acta pharmaceutica Sinica, 2010Co-Authors: Pingping Chen, Ning Zhao, Yeping Ruan, Yinghui WeiAbstract:The Mesaconitine and its major metabolites in the rat urine were identified by liquid chromatography and electrospray ionization tandem mass spectrometry. The rat urine was collected for consecutive 24 hours from the rat following intragastric infusion of Mesaconitine, subsequently which were enriched and purified using solid phase extraction. The metabolites of Mesaconitine in the rat urine were analyzed by the liquid chromatography and electrospray ionization tandem mass spectrometry. It is shown that the parent drug Mesaconitine and its metabolites were found in the rat urine, such as hypo-Mesaconitine glucuronic acid conjugate, 10-hydroxy-Mesaconitine, 1-O-demethyl Mesaconitine, deoxy-Mesaconitine and hypo-Mesaconitine. Among the five of metabolites, the hypo-Mesaconitine glucuronic acid conjugate (m/z 766) was first discovered as the aconitine in rats phase II metabolites, which revealed a new way of Mesaconitine metabolism in rats.
Angela Ameri - One of the best experts on this subject based on the ideXlab platform.
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effects of Mesaconitine on 3h noradrenaline uptake and neuronal excitability in rat hippocampus
Experimental Brain Research, 1998Co-Authors: Angela Ameri, Ulrike SeitzAbstract:Mesaconitine, one of the main alkaloids contained in Aconiti tubers, is a centrally acting analgesic without affinity to opioid receptors. It has been reported that the antinociception is due to an interaction with the noradrenergic system. In the present study, the effect of Mesaconitine on the uptake of noradrenaline and on neuronal activity was examined in rat hippocampus. Experiments were performed as a tudy of [3H]noradrenaline uptake into rat hippocampal synaptosomes. Mesoconitine inhibited [3H]noradrenaline uptake in a concentration-dependent manner with a Ki of 111.95±18 nM. In a further series of experiments, the effects of Mesaconitine on the extracellularly recorded population spike were investigated in rat hippocampal slices. At a concentration of 10 nM, Mesaconitine increased the amplitude of the postsynaptic population spike by 31.10%±6.7% of control and elicited one or two additional spikes. The presynaptic fiber spike and the field excitatory postsynaptic potential were not affected by this alkaloid. The enhancement of neuronal activity was abolished by 1 µM propranolol as well as by 1 µM timolol. It is concluded that mesoconitine increased the excitability in rat hippocampal pyramidal cells by an involvement of the noradrenergic system, with at least one mechanism being inhibition of noradrenaline uptake leading to an enhanced extraneuronal noradrenaline level.
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inhibition of stimulus triggered and spontaneous epileptiform activity in rat hippocampal slices by the aconitum alkaloid Mesaconitine
European Journal of Pharmacology, 1998Co-Authors: Angela AmeriAbstract:Abstract The aim of the present study was to investigate if the plant alkaloid, Mesaconitine, which has been reported to have antinociceptive effects via stimulation of the noradrenergic system, inhibits epileptiform field potentials. The experiments were performed as extracellular recordings on rat hippocampal slices. Epileptiform activity was induced by omission of Mg 2+ from the bathing medium or by addition of bicuculline and stimulus-evoked population bursts were recorded in the CA1 region. Spontaneous epileptiform activity was elicited by perfusing a nominally Mg 2+ -free bathing medium with high K + concentration (5 mM). Both stimulus-triggered and spontaneous epileptiform activity was attenuated in a concentration-dependent manner by Mesaconitine (30 nM–1 μ M). The inhibitory effect was rather variable in appearance when lower concentrations (30 and 100 nM) of Mesaconitine were applied. Pretreatment of the slices with the α -adrenoceptor antagonist yohimbine (1 μ M) prevented the effect of Mesaconitine. It is concluded that the inhibitory action of Mesaconitine at low concentration is mediated via α -adrenoceptors.
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effects of the aconitum alkaloid Mesaconitine in rat hippocampal slices and the involvement of α and β adrenoceptors
British Journal of Pharmacology, 1998Co-Authors: Angela AmeriAbstract:The effects of Mesaconitine, the main alkaloid contained in Aconiti tuber, were investigated by use of extracellular recordings of stimulus-evoked population spikes and field excitatory postsynaptic potentials (e.p.s.ps) in the CA1 region of rat hippocampal slices. At a concentration of 10 nM, Mesaconitine evoked excitations, which were manifested as an increase in the amplitude of the orthodromic spike and the appearance of multiple spikes following the first postsynaptic spike, without affecting the magnitude of paired-pulse facilitation. The increase in spike amplitude was persistent and was not reversed by up to 90 min of washout. At concentrations of 30 and 100 nM, the alkaloid produced a biphasic effect, that is an excitation followed by an inhibition without having any effect upon the field e.p.s.p. At concentrations above 100 nM, Mesaconitine suppressed the orthodromic population spike and the field e.p.s.p. The excitatory effect was also observed when electrical stimulation was stopped completely during the application of Mesaconitine (10 nM) and during the first 15 min of washout. The enhancement of the population spike and the appearance of multiple spikes induced by Mesaconitine (10–100 nM) were blocked by pretreatment with the β-adrenoceptor antagonists propranolol (1 μM) and timolol (1 μM), whereas the inhibitory effect was blocked by the α-adrenoceptor antagonists yohimbine (1 μM) and phentolamine (10 μM). However, when the β-adrenoceptor antagonist timolol was added 10 min after the application of Mesaconitine, it failed to block the long-lasting enhancement of the spike amplitude and the appearance of multiple population spikes. Application of the selective β-adrenoceptor agonist isoprenaline (500 nM) to the hippocampal slices induced an increase in the amplitude of the orthodromic population spike and elicited 2–3 additional spikes. Mesaconitine (10 nM) did not further potentiate this enhancement of the spike amplitude when added after a 15 min pretreatment with isoprenaline. Perfusion of forskolin, which directly activates adenylate cyclase, enhanced the population spike. Mesaconitine had no additional effect when applied after pretreatment with forskolin. It is concluded that the excitatory effects evoked by lower concentrations of the plant alkaloid Mesaconitine are mediated by stimulation of β-adrenoceptors and the consequent activation of intracellular processes which lead to the long-lasting changes in excitability. British Journal of Pharmacology (1998) 123, 243–250; doi:10.1038/sj.bjp.0701608
Pingping Chen - One of the best experts on this subject based on the ideXlab platform.
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analysis on the metabolites of Mesaconitine in the rat urine by liquid chromatography and electrospray ionization mass spectrometry
Acta pharmaceutica Sinica, 2010Co-Authors: Pingping Chen, Ning Zhao, Yeping Ruan, Yinghui WeiAbstract:The Mesaconitine and its major metabolites in the rat urine were identified by liquid chromatography and electrospray ionization tandem mass spectrometry. The rat urine was collected for consecutive 24 hours from the rat following intragastric infusion of Mesaconitine, subsequently which were enriched and purified using solid phase extraction. The metabolites of Mesaconitine in the rat urine were analyzed by the liquid chromatography and electrospray ionization tandem mass spectrometry. It is shown that the parent drug Mesaconitine and its metabolites were found in the rat urine, such as hypo-Mesaconitine glucuronic acid conjugate, 10-hydroxy-Mesaconitine, 1-O-demethyl Mesaconitine, deoxy-Mesaconitine and hypo-Mesaconitine. Among the five of metabolites, the hypo-Mesaconitine glucuronic acid conjugate (m/z 766) was first discovered as the aconitine in rats phase II metabolites, which revealed a new way of Mesaconitine metabolism in rats.
Fengrui Song - One of the best experts on this subject based on the ideXlab platform.
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metabolites and metabolic pathways of Mesaconitine in rat liver microsomal investigated by using uplc ms ms method in vitro
Acta pharmaceutica Sinica, 2013Co-Authors: Shu Liu, Fengrui Song, Ruixing Zhang, Zhiqiang LiuAbstract:Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of Mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 Mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of Mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of Mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of Mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of Mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes.
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exploring the ester exchange reactions of diester diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry
Rapid Communications in Mass Spectrometry, 2003Co-Authors: Yong Wang, Fengrui Song, Zhiqiang Liu, Lei Shi, Shuying LiuAbstract:The chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester-exchange reactions for aconitine-type diester-diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of Mesaconitine and hypaconitine standards with liquorice root. It was found that diester-diterpenoid aconitines were converted into lipo-alkaloids as well as monoester alkaloids by the decoction of aconite.