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1081-17-0, Name is 1-(4-Methoxyphenyl)-1H-pyrrole-2,5-dione, belongs to pyrrolines compound, is a common compound. Safety of 1-(4-Methoxyphenyl)-1H-pyrrole-2,5-dioneIn an article, once mentioned the new application about 1081-17-0.

Biotransformation of phenolic tetrahydroprotoberberines in plant cell cultures followed by LC-NMR, LC-MS, and LC-CD

A metabolic pathway of 2,3,10,11-oxygenated tetrahydroprotoberberines having the OH group on ring D was demonstrated. Metabolism of 13C- or D2-labeled precursors was studied in cell cultures of Macleaya, Corydalis, and Nandina species. The structures of alkaloid metabolites obtained from feeding experiments were determined by application of combined LC-NMR, LC-MS/MS, and LC-CD techniques. (S)-Tetrahydropseudoprotoberberine (5) was stereospecifically O-methylated to the 5-isomer (12) in cell cultures of three plant species. This 5-isomer was further N-methylated to the (5)-alpha-N-methyl salt (15), which was oxidized to produce the pseudoprotopine-type alkaloid (10) in cell cultures of Macleaya and Corydalis species. These transformations were the same as those of 2,3,9,10-oxygenated protoberberines. The tetrahydropseudoprotoberberines (5, 6, and 12) were dehydrogenated to pseudoprotoberberines (13, 16, and 14), respectively. Both the R- and 5-enantiomers of 5 were dehydrogenated in Macleaya cordata different from the case of 2,3,9,10-oxygenated protoberberines. Precursor 7, with OH groups at C-10 and C-11was O-methylated at C-10 in M. cordata and C. ochotensis var. raddeana, which was distinct from O-methylation in N. domestica, in which 7 was O-methylated at both C-11 and C-10. Stereoselective O-demethylation [(S)-S to (5)-18] occurred in N. domestica.

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Protective effect of protopine on the focal cerebral ischaemic injury in rats

Protopine, an isoquinoline alkaloidis, is known to produce many effects such as vasodilation, down-regulation of glutamate levels in brain and decrease of intracellular calcium. However, so far there is no report on the effect of protopine in cerebral ischaemia. In this study, the effect of protopine on the focal cerebral ischaemia was investigated in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-treated group and three doses of protopine-treated groups (0.98, 1.96 and 3.92 mg/kg). Protopine was intraperitoneally administered to rats once daily for 3 days prior to the ischaemia and 0.9% normal saline to rats in the vehicle-treated group in the same pattern. Rats in the sham-operated group were given 0.9% normal saline without the ischaemia. The focal cerebral ischaemia was induced by the middle cerebral artery occlusion for 24 hr via the intraluminal filament technique. The results showed that pre-treatment with protopine reduced the cerebral infarction ratio and serum lactate dehydrogenase activity, and improved the ischaemia-induced neurological deficit score and histological changes of brain in a dose-dependent manner. The further studies demonstrated that protopine increased superoxide dismutase activity in serum, and decreased total calcium and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)-positive cells in the ischaemic brain tissue in the middle cerebral artery occlusion rats. The results indicate that protopine is able to produce an effective protection on the injury caused by the focal cerebral ischaemia in rats possibly through the multiple effects of calcium antagonism, antioxidation and depression of cell apoptosis.

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Systematic exploration of Astragalus membranaceus and Panax ginseng as immune regulators: Insights from the comparative biological and computational analysis

Background: Immune system plays a decisive role for defending various pathogenic microorganisms. Astragalus membranaceus (AM) and Panax ginseng (PG) are two tonic herbs used in traditional Chinese medicine (TCM) as immune booster and help to control diseases with their healthy synergistic effect on immune system. Purpose: This study was aimed to investigate the promote effect and molecular mechanisms of AM and PG on immune system as booster and to control the target diseases using animal and computational systematic study. Methods: Computational models including absorption, distribution, metabolism, and elimination (ADME) with weighted ensemble similarity (WES) algorithm-based models and ClueGo network analysis were used to find the potential bioactive compounds targets and pathways, which were responsible for immune regulation. Viscera index analysis, proliferation activity of splenic lymphocytes and cytotoxic activity of NK cells assays were performed to validate the effect of AM and PG on immune system of long-term administrated mice. Metabonomic study of mice plasma was conducted to investigate effect of AM and PG on the endogenous metabolic perturbations, together with correlation analysis. Results: AM and PG simultaneously showed the ability to strengthen the immune system function including enhancement of spleen and thymus index, proliferation of splenic lymphocytes and cytotoxic activity of NK cells. Besides, the different molecular mechanisms of AM and PG on immune regulation were also investigated by analyzing the potential bioactive compounds, enzymes actions and pathways. Quercetin, formononetin and kaempferol were the main immune-related compounds in AM, while ginsenoside Ra1, ginsenoside Rh1 and kaempferol in PG. About 10 target proteins were found close to immune regulation, including acetylcholinesterase (ACHE, common target in AM and PG), sphingosine kinase 1(SPHK1), cytidine deaminase (CDA), and Choline O-acetyltransferase (CHAT). Glycerophospholipid metabolism was regulated in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were considered as the special pathway in AM groups. Energy metabolism and glycerolipid metabolism were the special pathways in PG groups. Conclusion: A novel comprehensive molecular mechanism analysis method was established and applied to clarify the scientific connotation of AM and PG as immune regulation, with similar herbal tonic effect provided in clinical practice of TCM, which can provide a new line of research for drug development (immune booster) using AM and PG.

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Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer’s Disease

Two new isoquinoline alkaloids, named fumaranine (2) and fumarostrejdine (10), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase-3beta inhibitory activities. Parfumidine (8) and sinactine (15) exhibited potent POP inhibition activities (IC50 99¡À5 and 53¡À2 muM, resp.).

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Screening of bioactive components from traditional Chinese medicine by immobilized beta2 adrenergic receptor coupled with high performance liquid chromatography/mass spectrometry

Traditional Chinese medicine (TCM) represents a valuable resource for lead compounds discovery. Given the complexity of TCM components, analytical methods play a key role in novel drug development. In our study, we established a high specific and reliable bio-active components screen system, where beta2 adrenergic receptor (beta2-AR) was immobilized on silica by non-covalent bonds and packed into a stainless steel column (4.6 ¡Á 50 mm, 7 mum) to form beta2-AR chromatography column. The column was further coupled with high performance liquid chromatography-time of flight tandem mass spectrometry (TOF-MS/MS). By utilizing this strategy, we successfully identified four beta2-AR-targeting compounds: tetrahydroberberine, tetrahydrocolumbamine, fumarine and corydaline from Corydalis Rhizome. The association constants between beta2-AR and tetrahydroberberine (9.04 ¡Á 104/M) as well as fumarine (4.30 ¡Á 104/M) were determined by frontal chromatography. We also found that these two compounds shared the identical binding site on immobilized beta2-AR with corresponding concentrations of 6.67 ¡Á 10?4 M and 5.88 ¡Á 10?4 M, respectively. The newly established method represents an efficient tool to identify the target specific natural compounds.

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Two new protopines argemexicaines A and B and the anti-HIV alkaloid 6-acetonyldihydrochelerythrine from Formosan Argemone mexicana

Two new protopine-type alkaloids, argemexicaine A (1) and argemexicaine B (2), along with thirteen known alkaloids, were isolated from MeOH extracts of Formosan Argernone mexicana L. (Papaveraceae). Physical and spectral analyses, particularly IR and thermo-modulated 1D and 2D NMR, were used to determine the transannular conformations of the isolated protopine-type alkaloids. The known benzo[c]phenanthridine (¡À)-6-acetonyldihydrochelerythrine (5) exhibited significant anti-HIV activity in H9 lymphocytes with EC50 and TI (Therapeutic Index) values of 1.77 mug/mL and 14.6, respectively.

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Berberis lycium Royle fruit extract mitigates oxi-inflammatory stress by suppressing NF-kappaB/MAPK signalling cascade in activated macrophages and Treg proliferation in splenic lymphocytes

Abstract: Although Berberis plant species have been advocated as immune modulators, information regarding their mechanism(s) of action is limited. Therefore, in the present study we assessed the efficacy of Berberis lycium Royle fruit extract (BLFE) in the attenuation of lipopolysaccharide (LPS)-induced oxi-inflammatory aggravation and concanavalin A (Con-A)-induced proliferation in murine peritoneal macrophages and lymphocytes, respectively. BLFE strongly suppressed production of the oxidative and inflammatory effector molecules nitric oxide (NO), reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), inflammatory cytokines (TNF-alpha/IL-6/IL-1beta/IFN-gamma) as well as chemokines (MCP-1 and RANTES), with a concomitant enhancement in heme oxygenase-1 (HO-1) and IL-10 levels. Subsequent mechanistic analysis revealed that BLFE strongly inhibited the phosphorylation of IkappaBalpha as well as MAPKs such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK), thereby directly resulting in the suppression of nuclear factor-kappaB (NF-?B) and c-Jun activation, ultimately culminating in the observed attenuation of inflammatory molecules. Additionally, BLFE appeared to mitigate Con-A-induced proliferation of Tregs (CD3+ CD4+ CD25+) thereby suggesting its modulatory effects on adaptive immune cells. UPLC?DAD?ESI-QTOF-MS/MS of BLFE revealed the presence of major bioactive phenolics and alkaloids including chlorogenic acid, rutin, catechin and quercetin 3-d-galactoside, berberine and magnoflorine, which could have synergistically contributed to the above findings. Overall, this work provides evidence that BLFE may be effective in the mitigation of inflammatory disorders, especially those associated with NF-kappaB/MAPK activation. Graphical abstract: [Figure not available: see fulltext.].

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Determination of selected isoquinoline alkaloids from mahonia aquifolia; Meconopsis cambrica; Corydalis lutea; Dicentra spectabilis; Fumaria officinalis; Macleaya cordata Extracts by HPLC-DAD and Comparison of Their Cytotoxic Activity

Alkaloids have protective functions for plants and can play an important role in living organisms. Alkaloids may have a wide range of pharmacological activities. Many of them have cytotoxic activity. Nowadays, cancer has become a serious public health problem. Searching for effective drugs with anticancer activity is one of the most significant challenges of modern scientific research. The aim of this study was the investigation of cytotoxic activity of extracts obtained from Corydalis lutea root and herb, Dicentra spectabilis root and herb, Fumaria officinalis, Macleaya cordata leaves and herb, Mahonia aquifolia leaves and cortex, Meconopsis cambrica root and herb on FaDu, SCC-25, MCF-7, and MDA-MB-231 cancer cell lines. The cytotoxic activity of these extracts has not been previously tested for these cell lines. The aim was also to quantify selected alkaloids in the investigated extracts by High Performance Liquid Chromatography (HPLC). The analyses of alkaloid content were performed using HPLC in reversed phase (RP) mode using Polar RP column and mobile phase containing acetonitrile, water and ionic liquid (IL). Cytotoxic effect of the tested plant extracts and respective alkaloid standards were examined using human pharyngeal squamous carcinoma cells (FaDu), human tongue squamous carcinoma cells (SCC-25), human breast adenocarcinoma cell line (MCF-7), human triple-negative breast adenocarcinoma cell line (MDA-MB-231). All investigated plant extracts possess cytotoxic activity against tested cancer cell lines: FaDu, SCC-25, MCF-7, and MDA-MB-231. The highest cytotoxic activity against FaDu, SCC-25, and MCF-7 cell lines was estimated for Macleaya cordata leaf extract, while the highest cytotoxic activity against MDA-MB-231 cell line was obtained for Macleaya cordata herb extract. Differences in cytotoxic activity were observed for extracts obtained from various parts of investigated plants. In almost all cases the cytotoxic activity of investigated plant extracts, especially at the highest concentration against tested cell lines was significantly higher than the activity of anticancer drug etoposide. Our investigations exhibit that these plant extracts can be recommended for further in vivo experiments to confirm their anticancer activity.

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Novel inhibitors of urease from Corydalis govaniana Wall.

A new compound govaniadine (1), along with three known tetrahydroprotoberberine-type alkaloids caseadine (2), caseamine (3), and protopine (4), were isolated from the plant Corydalis govaniana Wall. All alkaloids 1-4 exhibited a good urease enzyme inhibition with IC50 ¡À S.E.M. values of 20.2 ¡À 3.6, 38.9 ¡À 2.8, 66.7 ¡À 1.2, and 54.1 ¡À 1.2 muM, respectively, which are comparable to the standard inhibitor, acetohydroxamic acid (IC50 = 42.0 muM). None of these compounds showed inhibition against alpha-chymotrypsin. This is the first report of urease inhibiting tetrahydroprotoberberine-type alkaloids.

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ADDITIONAL ALKALOIDS FROM Glaucium squamigerum Kar. ET Kir.

A new quaternary alkaloid, (-)-beta-N-methylisocorypalminium hydroxide, was isolated from Glaucium squamigerum KAR. et KIR. in the form of iodide.In addition to the alkaloids already known to occur in this plant, i.e.allocryptopine (the main alkaloid), protopine, chelerythrine, sanguinarine, corydine, coptisine and berberine, additional alkaloids, i.e. (-)-chelidonine, (+/-)-chelidonine (diphylline) and chelirubine were also isolated from the non-quaternary fraction, while from the fraction of quaternary alkaloids (-)-beta-N-methylcanadinium iodide (the second main alkaloid), (-)-alpha-N-methylcanadinium iodide and (-)-beta-N-methylstylopinium iodide were isolated after conversion of the salts to iodides.Further the presence of small amounts of stylopine, canadine, scoulerine, corysamine, corytuberine, magnoflorine, alpha-N-methylstylopinium hydroxide and beta-N-methyltetrahydropalmatinium hydroxide were also detected.

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