Isoprenoid flavonoids isolated from Sophora davidii and their activities induces apoptosis and autophagy in HT29 cells.

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Two new alkaloids from Dendrobium nobile Lindl. exhibited neuroprotective activity, and dendrobine alleviated Aß1-42 -induced apoptosis by inhibiting CDK5 activation in PC12 cells.

Dendrobium nobile Lindl. is registered in the Chinese Pharmacopoeia as a traditional medicine. Phytochemical investigation of the ethanol extract of D. nobile Lindl. stems yielded three alkaloid compounds, including two new compounds dendroxine B (2) and denrine B (3) as well as one known compound dendrobine (1). Here, we identified the structure of these compounds using spectroscopic analyses and compared them with those described in previous studies. Compounds 1-3 were found to show protective effect against amyloid-ß 1-42 (Aß1-42 )-induced neurotoxicity in rat pheochromocytoma (PC12) cells, among which dendrobine exhibited the most significant neuroprotective effect. Hoechst 33342/propidium iodide staining indicated that dendrobine ameliorated Aß1-42 -induced apoptosis. Moreover, quantitative real-time polymerase chain reaction and western blot analysis analysis demonstrated that dendrobine suppressed the activation of cyclin-dependent kinase 5 (CDK5), upregulated Bcl-2 expression, and downregulated Bax, cyto-c, and caspase-3 expression. Molecular docking analysis and surface plasmon resonance assay suggested that dendrobine directly bound to CDK5 protein with a KD value of 2.05 × 10-4 M. In summary, alkaloids are the neuroprotective constituents of D. nobile Lindl., and dendrobine protected PC12 cells against Aß1-42 -induced apoptosis by inhibiting CDK5 activation.

Dihydrophenanthrenes and phenanthrenes from Dendrobium terminale.

Two previously undescribed dihydrophenanthrene derivatives (1 and 2) were isolated along with twelve known analogues from the whole plant of Dendrobium terminale. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis. The NMR data of known phenanthrene derivatives (7 and 9) were revised by 2D NMR. The isolated compounds were evaluated for cytotoxicity against three kinds of tumor cell lines (sw1990, HCT-116, and HepG2). Especially compounds 11 and 14 showed stronger antitumor effects, and the structure-activity relationship of these compounds was discussed.

Traffic light-type ratiometric fluorescence visual sensing of Cs+ in soybean oil based on dimension regulation of 2D perovskite nanosheets.

Determination of cesium ion in soybean oil is of high importance since the increasing risk from releasing of main component of nuclear waste cesium 137. The complex composition and high viscosity of soybean oil make it necessary to convert it into water phase by nitration before detection, so developing a simple, accurate and sensitive method for on-site sensing of Cs+ in soybean oil is still a big challenge. In this work, we report a traffic light-type ratiometric fluorescence strategy for the visual sensing of Cs+ in soybean oil based on dimensional regulation of two dimensional (PEA)2PbI4 perovskite nanosheets (NSs). The PEA+ in (PEA)2PbI4 NSs exchanged with Cs+ and lead to dimension of partial (PEA)2PbI4 NSs progressively increase from 2D to 3D CsPbI3 NCs. Resultantly, the fluorescence of (PEA)2PbI4 NSs decreases with a concomitant fluorescence enhancement of CsPbI3 NCs upon increasing the concentrations of Cs+, and the emission accordingly change from green, yellow to red with a high fluorescence colorimetric resolution up to 5.0 µM, make it successful to achieve on-site sensing of Cs+ in soybean oil just with naked eye in 5 min without any nitration, demonstrating a bright application future for determination of Cs+ in the soybean oil.

Glucosyloxybenzyl 2-isobutylmalates and phenolic glycosides from the flowers of Bletilla striata.

Four previously undescribed compounds, including three glucosyloxybenzyl 2-isobutylmalates (1-3), one phenolic glycoside (4), along with ten known compounds were isolated from the flowers of Bletilla striata. The structures and absolute configurations of the undescribed compounds were elucidated on the basis of HR-ESIMS, NMR spectroscopy, optical rotation value, and acid hydrolysis experiment. Cytotoxicity of the isolated compounds against A549, HCT-116, and SW1990 cells and protective effects of t-BHP-induced L02 cytotoxic were assayed. The antioxidant activities of the isolated compounds were also evaluated.

Dihydrophenanthrofurans and bisbibenzyl derivatives from the stems of Dendrobium nobile.

Two new dihydrophenanthrofurans (1 and 2) and two new bisbibenzyl derivatives (3 and 4) were isolated from the traditional Chinese medicinal plant Dendrobium nobile, along with four known compounds (5-8). The absolute configurations of compounds 1 and 4 were elucidated through extensive NMR and ECD spectroscopic analyses. New compounds showed no antimicrobial activity against four gram-positive bacterial strains and four gram-negative bacteria at the concentration of 1 mg/mL, but displayed significant cytotoxic activity against HepG2 human hepatic cell line with the IC50 values ranging from 1.25 µM to 19.47 µM.

A conventional chemical reaction for use in an unconventional assay: A colorimetric immunoassay for aflatoxin B1 by using enzyme-responsive just-in-time generation of a MnO2 based nanocatalyst.

The authors describe a colorimetric immunoassay for the model nalyte aflatoxin B1 (AFB1). It is based on the just-in-time generation of an MnO2 nanocatalyst. Unlike previously developed immunoassay, the chromogenic reaction relies on the just-in-time formation of an oxidase mimic without the aid of the substrate. Potassium permanganate (KMnO4) is converted into manganese dioxide (MnO2) which acts as an oxidase mimic that catalyzes the oxidation 3,3',5,5'-tetramethylbenzidine (TMB) by oxygen to give a blue colored product. In the presence of ascorbic acid (AA), KMnO4 is reduced to Mn(II) ions. This results in a decrease in the amount of MnO2 nanocatalyst. Hence, the oxidation of TMB does not take place. By adding ascorbate oxidase, AA is converted into dehydroascorbic acid which cannot reduce KMnO4. Based on these observations, a colorimetric competitive enzyme immunoassay was developed where ascorbate oxidase and gold nanoparticle-labeled antibody against AFB1 and magnetic beads carrying bovine serum albumin conjugated to AFB1 are used for the determination of AFB1. In presence of AFB1, it will compete with the BSA-conjugated AFB1 (on the magnetic beads) for the labeled antibody against AFB1 on the gold nanoparticles. This makes the amount of ascorbate oxidase/anti-AFB1 antibody-labeled gold nanoparticles, which conjugated on magnetic beads, reduce, and resulted in an increase of ascorbic acid. Under optimal conditions, the absorbance (measured at 652 nm) decreases with increasing AFB1 concentrations in the range from 0.1 to 100 ng mL-1, with a 0.1 ng mL-1 detection limit (at the 3Sblank level). The accuracy of the assay was validated by analyzing spiked peanut samples. The results matched well with those obtained with a commercial ELISA kit. Conceivably, the method is not limited to aflatoxins but has a wide scope in that it may be applied to many other analytes for which respective antibodies are available. Graphical abstract Schematic illustration of ascorbate oxidase (AOx)-mediated potassium permanganate (KMnO4)-responsive ascorbic acid (AA) for visual colorimetric immunoassay of aflatoxin B1 (AFB1) by coupling with hydrolytic reaction of AOx toward AA and the KMnO4-Mn(II)-TMB system [note: 3,3',5,5'-tetramethylbenzidine: TMB].

Selective antagonism of TRPA1 produces limited efficacy in models of inflammatory- and neuropathic-induced mechanical hypersensitivity in rats.

The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0.2), and orally bioavailable small molecule TRPA1 antagonist. AMG0902 reduced mechanically evoked C-fiber action potential firing in a skin-nerve preparation from mice previously injected with complete Freund's adjuvant, supporting the role of TRPA1 in inflammatory mechanosensation. In vivo target coverage of TRPA1 by AMG0902 was demonstrated by the prevention of AITC-induced flinching/licking in rats. However, oral administration of AMG0902 to rats resulted in little to no efficacy in models of inflammatory, mechanically evoked hypersensitivity; and no efficacy was observed in a neuropathic pain model. Unbound plasma concentrations achieved in pain models were about 4-fold higher than the IC90 concentration in the AITC target coverage model, suggesting that either greater target coverage is required for efficacy in the pain models studied or TRPA1 may not contribute significantly to the underlying mechanisms.

AMG2850, a potent and selective TRPM8 antagonist, is not effective in rat models of inflammatory mechanical hypersensitivity and neuropathic tactile allodynia.

TRPM8 has been implicated in pain and migraine based on dorsal root- and trigeminal ganglion-enriched expression, upregulation in preclinical models of pain, knockout mouse studies, and human genetics. Here, we evaluated the therapeutic potential in pain of AMG2850 ((R)-8-(4-(trifluoromethyl)phenyl)-N-((S)-1,1,1-trifluoropropan-2-yl)-5,6-dihydro-1,7-naphthyridine-7(8H)-carboxamide), a small molecule antagonist of TRPM8 by in vitro and in vivo characterization. AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %). When tested in a skin-nerve preparation, AMG2850 blocked menthol-induced action potentials but not mechanical activation in C fibers. AMG2850 exhibited significant target coverage in vivo in a TRPM8-mediated icilin-induced wet-dog shake (WDS) model in rats (at 10 mg/kg p.o.). However, AMG2850 did not produce a significant therapeutic effect in rat models of inflammatory mechanical hypersensitivity or neuropathic tactile allodynia at doses up to 100 mg/kg. The lack of efficacy suggests that either TRPM8 does not play a role in mediating pain in these models or that a higher level of target coverage is required. The potential of TRPM8 antagonists as migraine therapeutics is yet to be determined.

Aporphine alkaloids from the roots of Stephania viridiflavens.

Further investigation on the phytochemistry of the medicinal plant Stephania viridiflavens led to the isolation of a new naturally occurring aporphine alkaloid, (+)-6R, 6aS-isocorydine N(beta)-oxide (1), together with three known aporphine alkaloids: (+)-6R, 6aS-corydine N(beta)-oxide (2), (+)-N-methyl-laurotetanine (3) and (+)-stepharine (4). The structure and stereochemistry of 1 were determined on the basis of spectroscopic methods and confirmed by synthesis. Alkaloids 2-4 were isolated for the first time from this species.

[Simultaneous determination of residues of organochlorine and pyrethroid pesticides in tea by microwave assisted extraction solid phase microextraction-gas chromatography].

The issue of residues including organochlorine and pyrethroid pesticides in tea has made a great attention of researchers and customers in the world. Although some analytical methods have well been established to detect these pesticides, the sample preparations are generally laborious, time-consuming, and some of the procedures caused environmental pollution. Solid phase microextraction (SPME) is a novel sample preparation technique since it is of simplicity, high efficiency and solvent free. SPME was firstly developed to address the need to facilitate environment monitoring. In recent years, great efforts have been made in the analysis of pesticide residues in agricultural products by SPME. In this research, a microwave assisted extraction solid phase microextraction-gas chromatography (MAE-SPME-GC) was applied for the simultaneous determination of organochlorine and pyrethroid pesticides, such as benzene hexa chlorides (alpha-BHC, beta-BHC, gamma-BHC and delta-BHC), 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2, 2, 2-trichloroethane (o, p'-DDT), 2, 2-bis (4-chlorophenyl)-1, 1-dichloroethylene (DDE), 2, 2-bis (4-chlorophenyl)-1, 1-dichloroethane (DDD), 2-(2-chlorophenyl)-2-(4-chlorophenyl)-1, 1, 1-trichloroethane (p, p'-DDT), cypermethrin and fenvalerate. All the tested pesticides were baseline separated under the experimental conditions, except for DDD and o, p'-DDT. The concentration of each pesticide was calibrated by external standard method. The linearities were found to be in the correlation coefficient range of 0.970 5 to 0.998 4 for the tested pesticides between the mass concentrations and peak areas, except for fenvalerate. The recoveries, relative standard deviations and detection limits for the 10 pesticides were 64% - 121%, 10.4% -22.9%, and 1 - 50 ng/L, respectively. The proposed method was successfully applied to the determination of organochlorine pesticide residues in three kinds of teas from the local market. The experimental results demonstrated that MAE-SPME-GC was a fast, sensitive and green technique for the analysis of trace quantity of pesticides in solid substrate foods.