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Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.
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@#In order to study the involatile chemical components in Moutai-flavored distiller’s grains, the Moutai-flavored distiller’s grains were extracted with 75% ethanol, followed by extraction with petroleum ether, ethyl acetate, and n-butanol. Silica gel, ODS, sephadex LH-20, and preparative HPLC were used to separate and identify the petroleum ether and ethyl acetate layers.ESI-MS and NMR were used to identify the compounds, which were respectively identified as pentadecanoic acid (1), palmitic acid (2), trans-2-decenoic acid (3), n-nonyl octadecanoate (4), ethyl octadecanoate (5), ethyl linoleate (6), luric acid (7), 1, 3-dicaprylyl-2-linoleylglycerin (8), cyclic (phenylalanine-proline) (9), cyclo-(proline-leucine) (10), 3, 6-bis-(2-methylpropyl)-2,5-dione piperazine (11), 4-hydroxyphenethyl alcohol (12), 2,4-dihydroxybenzoic acid (13), stigmasterol (14), 2-furancarboxylic acid (15), valine (16), L-alanine acyl-L-proline (17), dihydroquercetin (18), 5, 7, 3'', 4''-tetrahydroxyflavonoids (19), quercetin (20), and naringenin (21). Compounds 1-21 were isolated from distiller’s grains for the first time.
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The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.
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Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.
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Limb and CNS expressed 1 like (LIX1L) is over-expressed in several types of tumors. However, the function of LIX1L in glucose metabolism and hepatocellular carcinoma (HCC) progression remains elusive. Here we report that LIX1L is over-expressed in human HCC tissues, which predicts unfavorable prognosis. LIX1L deficiency
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Screening active natural products, rapid identification, and accurate isolation are of great important for modern natural lead compounds discovery. We hereby reported the isolation of seven new neotecleanin-type limonoids (-), seven new limonoids with 5-oxatricyclo[5.4.0.11., 4.]hendecane ring system (-), and two new precursors (-) together with four known limonoids (-) from the root barks of . Their structures, including their absolute configurations, were elucidated based on analyses of HR-ESI-MS, 1D/2D NMR, ECD spectrum calculations and single-crystal X-ray diffraction techniques. Compounds , , , , , , showed significant anti-inflammatory activities in LPS-induced RAW 264.7 cell line, BV2 microglial cells, and -stimulated THP-1 human monocytic cells. Walrobsin M () exhibited anti-inflammatory activity with IC value of 7.96±0.36 μmol/L, and down-regulated phosphorylation levels of ERK and p38 in a dose-dependent manner.
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The modernization of quality standard for traditional Chinese medicine (TCM) is an important prerequisite for the internationalization of TCM.It is also an important guarantee for the rapid and healthy development of TCM industry.In recent years,we have strived to make TCM quality more in line with the needs of modern development.An important work is to improve and perfect the quality standard of TCM,which has obtained certain result.There are also lots of rooms to improve.From the point of material basis of TCM,this paper discussed requirements and further development direction of TCM quality standard under the background of achieving modernization and internationalization.
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@#(±)-Praeruptorin A(PA)was used as the standard reference substance to establish a new method of substitute for reference substance. The contents of both(±)-praeruptorin B(PB)and(+)-praeruptorin E(PE)were calculated by the method. The major content of coumarins in different processing materials could be gained by determining the content of(±)-praeruptorin A, which could provide scientific evidence for the research on pharmacology discrepancy and quality standards. The method was carried out on a Welch Materials Ultimate XB-C18 column(4. 6 mm×250 mm, 5 μm), with a gradient mobile phase of methanol and water at the flow rate of 1. 0 mL/min. The column temperature was 30 °C and detection wavelength was set at 322 nm. According to this method, the relative correlation factors(f)of(±)-praeruptorin B and(+)-praeruptorin E were determined as 0. 787 2 and 0. 969 0, respectively. After determine the contents of 15 batches of materials from different sources, no significant differences between substitute method and external standard method were observed. It was a feasible and credible method to determine the content of major coumarins in Peucedani Radix with different processing materials. The results showed lower contents of coumarins in processing materials than in raw materials.
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As a part of our ongoing research program to isolate novel phragmalin limonoids from the stem bark of Chukrasia tabularis var. velutina, two new phragmalin limonoids orthesters, tabularin Q (1) and tabulalide O (4), along with two known compounds tabularin C (2) and tabularin H (3) were isolated. Their structures were elucidated by means of extensive 1D and 2D spectroscopic analyses which included HSQC, HMBC, and ROESY experiments and HR-ESI-MS.
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Herba Epimedii (named Yinyanghuo in Chinese) of the family Berberidaceae is one of the most famous traditional Chinese medicines (TCMs) recorded in the pharmacopoeia of the People's Republic of China.Total flavonoids of Epimedium (TFE) are considered to be its active components.TFE content was measured by ultraviolet method and its representative constituents,icariin and epimedin C,were determined by high performance liquid chromatography.The test results from 36 samples of 4 species showed that the contents differed significantly in different species.The average data of the summation (icariin and epimedin C) content were 20.83,7.61,14.43,23.29 mg/g in Epimedium pubescens Maxim.,E.koreanum Nakai.,E.brevicornum Maxim.,E.sagittatum (Sieb.Et Zucc.) Maxim.,respectively.Both E.sagittatum and E.pubescens performed better than the other two batches.E.sagittatum hardly has any circulation in Chinese herbal medicine market.The results showed that E.pubescens,which had much more amounts of icariin,epimedin C and TFE than those of other species,has a better quality and may be considered as potential anti-osteoporosis drug.
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Objective To study the chemical constituents from the roots of Gypsophila pacifica. Methods The chemical constituents were isolated by various column chromatographic methods and their structures were identified by spectral data together with physicochemical analysis. Results Five compounds were isolated and identified as 3-O-β-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosyl gypsogenin 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranoside (1), 3-O-β-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosyl quillaic acid 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranoside (2), 3-O-β-D-galactopyranosyl-( 1→ 2 )-[β-D-xylopyranosyl-( 1→ 3 ) ]-β- D-glucuronopyranosyl gypsogenin 28-O-β-D-glucopyranosyl-( 1→ 3 )-[β-D-xylopyranosyl-( 1→4 ) ]-α-L-rhamnop yranosyl-( 1 → 2 )-β-D-fucopyranoside (3),3-O-β-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosyl quillaic acid 28-O-β-D-glucopyranosyl-( 1→ 3 )-[β-D-xylopyranosyl-( 1→4 ) ]-α-L-rhamnopyranosyl-( 1→2 )-β-D-fucopyranoside ( 4), 3-O-β-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosyl quillaic acid 28-O-α-L-arabinopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranoside (5). Conclusion The five compounds are isolated from this plant for the first time.
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<p><b>OBJECTIVE</b>To study the chemical constituents in the introduced Coleus forskohlii.</p><p><b>METHOD</b>The chemical constituents were isolated by column chromato-graphy. The structures were elucidated on the basis of IR, MS, 1H-NMR and 13C-NMR experiments.</p><p><b>RESULT</b>Eight compounds were obtained, the structures of which were identified as cytochalasin B (1), N-benzoyl-L-phenylalaninol (2), 3,6-dibenzyl-2,5-dioxopiperazine (3), 2-furoic acid (4), vanillic acid (5), loliolide (6) and forskolin D (7).</p><p><b>CONCLUSION</b>Compounds 1-6 were isolated from the genus Coleus for the first time.</p>
Subject(s)
Coleus , Chemistry , Plant Extracts , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To study on the chemical constituents of effective part of Semen Ziziphi Spinosae.</p><p><b>METHOD</b>The sample was extracted with methanol and purified by macroporous resin. The structures were identified by high performance liquid chromatography/electrospray ionization with multi-stage tandem mass spectrometry.</p><p><b>RESULT</b>Thirteen compounds were identified from the effective part of Semen Ziziphi Spinosae.</p><p><b>CONCLUSION</b>The method is simple and rapid for the identification of the flavonoids and triterpenoid saponins from Semen Ziziphi Spinosae.</p>
Subject(s)
Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Chemistry , Flavonoids , Chemistry , Saponins , Chemistry , Semen , Chemistry , Spectrometry, Mass, Electrospray Ionization , MethodsABSTRACT
AIM:To obtain new typical compounds with dual mechanism,antagonizing Ca2+and inhibiting acetylcholinesterase,on Alzheimer's disease.METHODS:Resorcinol was chosen as primitive substrate,and AD-mix-β as asymmetrically dihydroxylated reagent;all products were screened against acetylcholinesterase in vitro.RESULTS:cis-3′R,4′R-disubstituted angular dihydropyranocoumarins were synthesized enantioselectively,however,its inhibitory activity on acetylcholinesterase is distinctively lower than that of cis-3′R,4′R-disubstituted linear dihydropyranocoumarins.
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AIM:Bioactive constituents were expected to be obtained from the roots of Angelica morri Hayata. METHOD:They were extracted with 95% alcohol and isolated by using column chromatography and recrystallization methods. The structures were elucidated by means of physico-chemical data and UV,IR,1HNMR, 13CNMR,and EIMS. The inhibitory effect on the constriction of rat aortic rings was induced by K+ or Ca2+. RESULT:3′S-(-)-hamaudol,3′S-(-)-Ο-acetylhamaudol,3′R-(+)-hamaudol,and (±)-hamaudol were isolated from the pieces of Radix Angelica Morri. The inhibitory rate of 3′S-(-)-Ο-acetylhamaudol and (±)-hamaudol on the above pharmacologic model appears the relation of quantity response. CONCLUSION:All the above compounds were found in this species for the first time,and(±)-hamaudol is a new. One of effect mechanisms of 3′S-(-)-Ο-acetylhamaudol and (±)-hamaudol diluted aorta could contribute to be inhibiting Ca2+ influx of vascular smooth muscle.
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AIM To study the chemical constituents of Peucedanum decursivum. METHODS Various column chromatographies with silica gel and HPLC were employed for the isolation and purification. The structures of the compounds were elucidated on basis of spectral analyses and chemical methods. RESULTS Seven compounds were isolated from the roots of Peucedanum decursivum (Miq.) Maxim. 1 is 3′(S)-hydroxy-4′(R)-angeloyloxy-3′,4′-dihydroxanthyletin, named Decursitin D; 2 is 3′(S)-acetoxy-4′(R)-hydroxy-3′,4′-dihydroxanthyletin, named decursitin F; the others are 3′(S)-acetoxy-4′(R)-angeloyloxy-3′,4′-dihydroxanthyletin (3), Pd-C-IV (4), Pd-C-II (5), (+)-3′S-decursinol (6) and (+)-trans-decursidinol (7). CONCLUSION Compounds 1 and 2 are new compounds, while compounds 6 and 7 were isolated from Peucedanum decursivum (Miq.) Maxim for the first time.
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Object In order to control the quality of crude drug, the total flavonoids of Epimedium koreanum Nakai were investigated Methods By repeated chromatographic methods 13 compounds were isolated and purified, and their structures were elucidated by physicochemical properties and spectroscopic methods (UV, IR, 1HNMR, 13 CNMR, HMBC, EI MS) Results They were identified as icariside II (Ⅰ), icariside I (Ⅱ), epimedoside C (Ⅲ), epimedin B (Ⅳ), icariin (Ⅴ), hyperoside (Ⅵ), hexandraside E (Ⅶ), anhydroicaritin (Ⅷ), maltol (Ⅸ), demethylanhydroicaritin (Ⅹ), insistol (Ⅺ), epimedoicarisoside A ( ⅩⅡ ) and (+) cycloolivil ( ⅩⅢ ) Conclusion Compounds Ⅶ, Ⅺ, ⅩⅢ were isolated from E koreanum for the first time, and Ⅶ was obtained from the plants of Epimedium L for the first time
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Object To investigate the chemical constituents of Epimedium koreanum Nakai.Methods Separation was performed by HPLC on a Merck LiChroCAR analytical column with the mobile phase consisting of acetonitrile-water-acetic acid as gradient eluent at the flow rate of 1 mL/min, the UV detection was set at 270 nm and TIC was recorded by an electrospray ionization mass spectrometer in positive mode. Results Nine compounds were identified by HPLC-MS2. Conclusion The method is rapid and accurate to identify the chemical constituents of the natural product.
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Chemical constituents of the aerial parts of Qianhu were compared with those present in the roots by RP-HPLC. It was found that the constituents in aerial parts of Peucedanum praeruptorum are similar and higher in content than that in the roots. So it is possible that the aerial parts can be used instead of the roots of the plant. But the chemical constituents in the aerial parts and the roots of P. decursivum are quite different, rendering it impossible to use the aerial parts instead of the roots of the plant.
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Objective To observe the effects of total flavones from Herba Epimedii(TFHE)on the experimental myocardial ischemia and hemorheology of animals.Methods The model of acute myocardial ischemia of rats was established with pituitrin and the model of acute blood stasis was established with high-molecular dextran.The effects of TFHE on the electrocardiogram J-point of acute myocardial ischemia model and the hemorheology of acute blood stasis model were observed.Besides these,the effects of TFHE on coaglutaion time in mice were observed.Results As compared with the model groups,high-,middle-,and low-dosage groups(24,12,and 6 mg/kg)of TFHE could obviously improve the abnormal electrocardiogram J-point of acute myocardial ischemia model,also could effectively prevent the ascending of whole blood viscosity(high-,middle-,and low-shear rate),packed erythrocyte volume,and fibrinogen.High-and low-dosage groups(34 and 17 mg/kg)of TFHE could obviously lengthen the coaglutaion time in mice.Conclusion The results suggest that TFHE possesses protective effects on ischemic myocardium,which may better hemorheology,decrease the whole blood viscosity,prevent blood from coagulating and improve the circulatation of coronary artery.