Molecular Mechanism of Curcumin Derivative on YAP Pathway against Ovarian Cancer.

The purpose of this study is to study the effect of curcumin derivative WZ10 on the proliferation, invasion and apoptosis of ovarian cancer OVCAR3 cells, and to explore its mechanism. MTT assay was used to detect the effect of WZ10 on the proliferation of ovarian cancer OVCAR3 cells; Annexin V/PI double staining flow cytometry was used to detect the effect of WZ10 on cell apoptosis; Transwell method was used to detect the effect of WZ10 on cell invasiveness; Western blot was used to investigate the effect of WZ10 Mechanisms affecting OVCAR3 activity in ovarian cancer in vitro. Our results show that WZ10 treatment could significantly inhibit the proliferation and invasion of OVCAR3 cells, induce apoptosis of OVCAR3 cells in a dose-dependent manner. After knockdown of Hippo expression with sh-RNA, further combined treatment with WZ10 had no significant image on ovarian cancer OVCAR3 cells. In conclusion: WZ10 can significantly inhibit the proliferation of OVCAR3 cells, reduce cell invasion and proliferation by downregulating the activation of Hippo-YAP pathway, and induce cell apoptosis.

[Secondary metabolites of endophyte Hypoxylon sp. HD-2014 from Uncaria rhynchophylla].

This study aims to investigate the compounds in the product of rice fermented with endophyte Hypoxylon sp.HD-2014 from Uncaria rhynchophylla.To be specific, normal-phase, MCI, Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was used to yield 12 compounds.Through spectral data analysis and comparison with previous reports, they were identified as methyl(E)-5-hydroxymethyl-6,7-dihydroxy-4,5-epoxy-octanoate-2-ene(1),(2E,6E)-nona-2,6,8-triene-4,5-diol(2), 8-O-(R)-methoxynodulisporin A(3), 3-nitropropionic acid(4), 3-nitropropionic acid methyl ester(5), 3,4-dihydroxy-phenylethanol(6), 2,4-dichlorobenzoic acid(7), cis-4-hydroxyscytalone(8), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(9), isosclerone(10), 4H-1-benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxyl-methyl)-2-methy(11), and 5-methylmellein(12), respectively.Compounds 1 and 2 were identified for the first time.In vitro cytotoxicity test indicated that compounds 1-12 had no significant inhibitory effect on A549 and HepG2 cells.Antimicrobial susceptibility testing revealed that compound 3 showed synergistic effect with the positive control chloramphenicol.

[Research practice and strategy of resource utilization of residues for edible medicinal plants under background of Big Health].

In recent years, with the acceleration of population aging in China, the frequent occurrence of chronic diseases, and the increase in the number of sub-health groups, people began to seek ways to maintain health in line with the laws of nature. Healthy China has become a national strategy, and the Big Health industry has ushered in a golden period of development. In this context, the concept of medicine and food homology and edible medicinal substances which have guided Chinese people to pursue health since ancient times have ushered in significant and favorable development opportunities, and the industrial scale has gradually expanded. The development and utilization of edible medicinal plants have also become an important research direction. In the industrialization process of modern health care and edible medicinal products, a large number of drug residues are often abandoned due to ineffective utilization, resulting in a huge waste of resources and increasing the pressure on the ecological environment. Under the guidance of the homology theory of medicine and food, based on the recycling strategy of Chinese medicine resources, this paper analyzed the inherent common characteristics such as physical and chemical properties and biological activity of Chinese medicine residues of edible medicinal plants and put forward some suitable resource utilization strategies and suggestions in combination with the current situation of resource development and utilization of Chinese medicine residues of edible medicinal plants, in order to promote the high-value development and utilization of medicinal and edible resources, and extend the industrial chain of edible medicinal resources, thereby empowering Big Health industry and facilitating Healthy China.

[Hydrolyzable tannins from flowers of Punica granatum and their anti-diabetic activities].

To investigate the active components against diabetes, the present study isolated eight hydrolyzable tannins from the ethyl acetate extract of Punica granatum flowers by MCI, reversed-phase chromatography(ODS), Sephadex LH-20 chromatography, and HPLC, and the structures were elucidated as 1-O-galloyl-6-O-feruloyl-ß-D-glucose(1), 1,2,3,4,6-penta-O-gally-ß-D-glucopyranose(2), punicafolin(3), corilagin(4), telimagrandin Ⅰ(5), 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-ß-D-glucose(6), heterophylliin A(7), and eugeniin(8) on the basis of spectral data and literature records. Among them, compound 1 is a new compound, and compounds 5-8 were isolated from this species for the first time. All isolated compounds were tested for inhibitory activities against α-glucosidase and DPP-Ⅳ. The results indicated that compounds 2, 3, and 5-8 showed significant inhibitory activities against α-glucosidase, while compounds 1 and 4 exhibited moderate inhibitory activities. Compounds 5, 7, and 8 showed moderate inhibitory effects on DPP-Ⅳ. In addition, the type of enzyme inhibition of compound 5 was determined.

(±)-Heterocageflavone, anti-inflammatory isoprenylated flavonoids with a tricyclo[5.3.1.03,8]undecane moiety from Artocarpus heterophyllus.

(±)-Heterocageflavone (1), a pair of enantiomeric isoprenylated flavonoids, were isolated from Artocarpus heterophyllus. Compound 1 incorporates an unusual tricyclo[5.3.1.03,8]undecane moiety, forming a unique caged polycyclic system. The structures of the pair were determined by spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction. Compound 1 showed significant inhibitory activity against LPS-induced NO production in RAW264.7 cells with an IC50 value of 49.2 µM.

Set of Cytochrome P450s Cooperatively Catalyzes the Synthesis of a Highly Oxidized and Rearranged Diterpene-Class Sordarinane Architecture.

Cytochrome P450s are one of the most versatile oxidases that catalyze significant and unique chemical transformations for the construction of complex structural frameworks during natural product biosynthesis. Here, we discovered a set of P450s, including SdnB, SdnH, SdnF, and SdnE, that cooperatively catalyzes the reshaping of the inert cycloaraneosene framework to form a highly oxidized and rearranged sordarinane architecture. Among them, SdnB is confirmed to be the first P450 (or oxidase) that cleaves the C-C bond of the epoxy residue to yield formyl groups in pairs. SdnF selectively oxidizes one generated formyl group to a carboxyl group and accelerates the final Diels-Alder cyclization to furnish the sordarinane architecture. Our work greatly enriches the enzyme functions of the P450 superfamily, supplies the missing skills of the P450 synthetic toolbox, and supports them as biocatalysts in further applications toward the synthesis of new chemical entities.

Anti-inflammatory Dimeric Benzophenones from an Endophytic Pleosporales Species.

Eight new polyketides, including three dimeric benzophenones, named dipleosporones A-C (1-3), three benzophenones (4-6), one xanthone (7), and one phenylbenzoate (8), along with seven known polyketides (9-15) were isolated from the fungus Pleosporales sp. YY-4. The structures of the new compounds were established on the basis of spectroscopic methods, including high-resolution electrospray ionization mass spectrometry and one- and two-dimensional nuclear magnetic resonance. This is the first report of a benzophenone dimer connection via a C bridge from natural sources. An anti-inflammatory assay indicated that the dimeric benzophenones (1-3) inhibited lipopolysaccharide-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values ranging from 8.8 to 18.1 µM, being more potent than the positive control, dexamethasone (IC50 = 22.2 µM).

Efficient performance of magnesium oxide loaded biochar for the significant removal of Pb2+ and Cd2+ from aqueous solution.

Lead (Pb) and cadmium (Cd) are considered as a typical heavy metals in aqueous solution, which may pose adverse health effects on human beings. For the removal of these two pollutants, magnesium oxide (MgO) was successfully immobilized onto eucalyptus biochar (BC) matrix via simple and cost-effective pyrolysis process of MgCl2-pretreated eucalyptus biomass under high temperature (500 °C). Synthesized MgO nanoparticles-biochar composites (MBC) exhibited superior removal performance for target pollutants, and achieve 99.9% removal efficiency for Pb(II) and Cd(II) at optimum conditions (0.02 g, pH in range of 4-7, and reaction time 120, 240 min). Furthermore, the maximum theoretical adsorbing amount of MBC was 829.11 mg/g for Pb(II) and 515.17 mg/g for Cd(II). Pseudo-second-order model and Langmuir models were well-determined for isotherm and adsorption kinetics. FTIR, XRD, and XPS analysis revealed that precipitation and ion exchange was of great importance for the removal of contaminants. Besides, cation-π interaction and complexation from the carbon-containing functional groups should not be neglected. Considering the advantage of low-cost, facile preparation, and brilliant adsorption capacity, it is anticipated that MBC has a promising prospect for the broad application in Pb(II)/Cd(II)-containing wastewater treatment.

[Two newly recorded species of plants in Jiangxi province].

Based on the investigation of wild medicinal plant resources in Dexing city, Jiangxi province, and the collected plant specimens, which were identified by taxonomy, two new record species of geographical distribution were found, which are Meehania zheminensis A. Takano, Pan Li & G.-H. Xia and Corydalis huangshanensis L.Q.Huang & H.S.Peng. The voucher specimens are kept in Dexing museum of traditional Chinese medicine. In this paper, the new distribution species were reported, which provides valuable information for further enriching and supplementing the species diversity of medicinal plant resources in Jiangxi province.

[Scientific research on selection of medicinal herbs of Chloranthaceae based on materia medica theory].

The plants of Chloranthaceae are widely distributed and rich in resources in our country, records of ancient herbs indicaded that various species of plants of Chloranthaceae can be used for medicinal purposes, especially the Sarcandra glabra which with the least toxicity and possessed the function of clearing heat and cooling blood, activating blood to eliminate spots and removing wind and dredging collaterals. Based on the theory of herbage and by the method of consulting the past herbal literature, we summarized and analyzed the medicinal history, distribution characteristics of herbage geography, characteristics of herbage ecology, standard collection situation and the modern toxicology research of Chloranthaceae plants. Therefore we explained the scientificity for selection of medicinal herbs of Chloranthaceae plants, and provided a theoretical and scientific basis for further research of Chloranthaceae plants.

Simultaneous determination of kaempferol, quercetin, mangiferin, gallic acid, p-hydroxybenzoic acid and chlorpheniramine maleate in rat plasma after oral administration of Mang-Guo-Zhi-Ke tablets by UHPLC-MS/MS and its application to pharmacokinetics.

Mang-Guo-Zhi-Ke tablets (MGZKTs) is an effective Chinese patent medicine. It contains mango leaf extract as the main raw material and the antihistamine drug, chlorpheniramine maleate is included in the formulation. However, its pharmacokinetic effect is rarely reported. A highly sensitive, reliable and rapid high-throughput method using ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was used to simultaneously determine kaempferol, quercetin, mangiferin, p-hydroxybenzoic acid, gallic acid and chlorpheniramine maleate in rat plasma after oral administration of MGZKTs. The method was successfully developed and fully validated to investigate the pharmacokinetics of MGZKTs. Chloramphenicol and clarithromycin were used as internal standards (IS). A practicable protein precipitation procedure with methanol was adopted for sample preparation. The samples were separated on an Acquity UHPLC Syncronis C18 column (100 × 2.1 mm, 1.7 µm) using 0.1% formic acid-acetonitrile as the mobile phase. The flow rate was set at 0.4 mL/min. The obtained calibration curves were linear in the concentration range of ~1-1000 ng/mL for plasma (r > 0.99). Method validation results met the criteria reported in the US Food and Drug Administration guidelines. Quercetin, p-hydroxybenzoic acid and kaempferol were absorbed rapidly and reached the peak concentration between 0.16 and 0.25 h. This validated that the UHPLC-MS/MS method was successfully applied to study the pharmacokinetic parameters of the six compounds in rat plasma after oral administration of MGZKTs. This evidence will be useful for the clinical rational use of Mang-Guo-Zhi-Ke tablets.

Protective effects of Salvia miltiorrhiza on adenine-induced chronic renal failure by regulating the metabolic profiling and modulating the NADPH oxidase/ROS/ERK and TGF-ß/Smad signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic renal failure (CRF) is defined as a progressive and irreversible loss of renal function and associated with inflammation and oxidative stress. Salvia miltiorrhiza (SM) is an important Chinese herb used in traditional Chinese medicine for treating cardiovascular diseases. The previous studies showed the SM exhibited significant protective effects on CRF. In this present study, the metabolic profiling changes and action mechanism of SM on CRF were explored. AIMS OF THE STUDY: The aims of this study were to illustrate the metabolic profiling changes of adenine induced CRF and analyze the protective effects and action mechanisms of SM ethanol extract (SMEE) and water extract (SMWE). MATERIALS AND METHODS: The animals were divided into normal group, CRF model group, Huangkui capsule-treated group, SMEE-treated group and SMWE-treated group. The UPLC-QTOFMS coupled with multivariate statistical methods were used to explore the changes of metabolic profile in plasma, urine and renal tissue from CRF rats simultaneously after treatment with SMEE and SMWE. Hematoxylin eosin (HE) staining and Masson staining were applied to observe pathological changes in renal tissue. Biochemical indicators including serum urea nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured according to the manufacturer's instructions of kits. Furthermore, HK-2 cell damaged model induced by ISF was established to access the protective effects and action mechanism. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine the reactive oxygen species (ROS) and Western blot was applied to analyze the expression of pathogenesis-related proteins in different groups. RESULTS: The results showed that the ethanol extract (SMEE) and water extract (SMWE) of SM significantly inhibited the elevation of serum creatinine (Scr), blood urea nitrogen (BUN), urine protein (UP) and indoxyl sulfate (ISF) in adenine-induced CRF rats, especially SMEE exhibited more significant effects. Moreover, SM extracts obviously improved the symptoms of glomerular and tubular atrophy, focal calcium deposits, interstitial fibrosis, interstitial inflammation, and renal tissues. By metabolomics analysis, fifty-nine metabolites (thirteen in plasma, twenty-seven in urine and nineteen in kidney tissue) were up-regulated or down-regulated and contributed to CRF progress. After treatment of SM extracts, the altered metabolites were restored back to normal level. These potential biomarkers underpinning the metabolic pathways are including phenylalanine metabolism, pyrimidine metabolism, purine metabolism and tryptophan metabolism. Furthermore, SM extracts prevent epithelial-mesenchymal transition (EMT) of human renal tubular epithelial (HK-2) cell by inhibiting NADPH oxidase/ROS/ERK and TGF-ß/Smad signaling pathways. CONCLUSIONS: SMEE and SMWE can significantly alleviate adenine-induced CRF via regulation of the metabolic profiling and modulation of NADPH oxidase/ROS/ERK and TGF-ß/Smad signaling pathways, which provided important supports for the development of protective agent of SM for CRF.

Comparative analysis of 15 chemical constituents in Scutellaria baicalensis stem-leaf from different regions in China by ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry.

Scutellaria baicalensis is a traditional Chinese herbal medicine containing multiple components, which has been extensively used in clinics to treat epidemic febrile disease and hyperactivity cough. To get a deeper understanding about Scutellaria baicalensis stem-leaf resources, we analyzed 15 chemical constituents in 35 batches of Scutellaria baicalensis stem-leaf from eight regions in China. A rapid, simple, and sensitive method using ultra-high performance liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry has been developed for the first time to simultaneously determine 15 chemical constituents (including phenolic acids and flavonoids) in Scutellaria baicalensis stem-leaf. Sufficient separation of 15 target constituents was achieved on a Waters Acquity UPLC BEH C18 (2.1 mm × 100 mm, 1.7 µm) column within 14 min under the optimized chromatographic conditions. The established method was validated and showed good linearity, precision, repeatability, stability, and recovery and was successfully applied for the simultaneous determination of the 15 chemical constituents in these samples. Hierarchical clustering analysis and principal components analysis were performed to estimate and classify these samples based on the contents of the 15 chemical constituents. This study provided theoretical basis and scientific evidence for the development and utilization of Scutellaria baicalensis stem-leaf resources.

Comparative Analysis of the Major Chemical Constituents in Salvia miltiorrhiza Roots, Stems, Leaves and Flowers during Different Growth Periods by UPLC-TQ-MS/MS and HPLC-ELSD Methods.

Salvia miltiorrhiza is a traditional Chinese herbal medicine containing multiple components that contribute to its notable bioactivities. This article investigated the distribution and dynamic changes of chemical constituents in various parts of S. miltiorrhiza from different growth periods. An ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UPLC-TQ-MS/MS) and high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD) methods were developed for accurate determination of 24 compounds (including phenolic acids, flavonoids, triterpenes, and saccharides) in S. miltiorrhiza. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. Results indicated that there were category and quantity discrepancies in different parts of the plant, for the roots mainly contained salvianolic acids and tanshinones, and most of the saccharides are stachyose. In the aerial parts, salvianolic acids, flavonoids, and triterpenes, except the tanshinones, were detected, and the saccharides were mainly monosaccharides. Dynamic accumulation analysis suggested the proper harvest time for S. miltiorrhiza Bunge was the seedling stage in spring, and for the aerial parts was July to August. This study provided valuable information for the development and utilization value of the aerial parts of S. miltiorrhiza and was useful for determining the optimal harvest time of the plant.

Comparative Pharmacokinetics of three major bioactive components in rats after oral administration of Typhae Pollen-Trogopterus Feces drug pair before and after compatibility.

BACKGROUND: Typhae Pollen (TP) and Trogopterus Feces (TF) are well-known traditional medicine in china which widely used for thousands of years as drug pair called Shixiao San for treatment of blood stasis syndrome, specially shown great efficacy in gynecological disease. Typhaneoside, vanillic acid and p-coumaric acid are the main bioactive components of Typhae Pollen. This study was carried out for comparing the pharmacokinetic profile of these three major bioactive components in rats after oral administration of Typhae Pollen-Trogopterus Feces (TP-TF) drug pair before and after compatibility. METHODS: A sensitive and rapid UPLC-TQ/MS method has been developed for simultaneous quantification of the three main bioactive compounds in blood at different time points after oral administration of Typhae Pollen (TP) and the combination with Trogopterus Feces (TF). RESULTS: There were significant differences of C(max), T(max), T(1/2) and AUC(0~t) for three bioactive compounds among the groups, for typhaneoside with the most highest plasma concentration of 370.86 ± 315.71 ng/mL and more longer T(max) in TP-TF co-decoction group (C(M)); for vanillic acid, TP-TF co-decoction group (C(M)) had a good absorption with C(max) (3870.99 ± 2527.99 ng/mL) and T(max) (1.47 ± 3.20 h); for p-coumaric acid, it had similar pharmacokinetic characteristics with vanillic acid. CONCLUSIONS: The three bioactive components in Typhae Pollen (TP) were simultaneously determined by UPLC-TQ/MS and had a good absorption in rat plasma after the combination with Trogopterus Feces (TF).

Copper-Catalyzed Ligand-Free Amidation of Benzylic Hydrocarbons and Inactive Aliphatic Alkanes.

An efficient copper-catalyzed amidation of benzylic hydrocarbons and inactive aliphatic alkanes with simple amides was developed. The protocol proceeded smoothly without any ligand, and a wide range of N-alkylated aromatic and aliphatic amides, sulfonamides, and imides were synthesized in good yields.