Stereochemical insights into neuroprotective alkaloids from the aerial parts of Emilia sonchifolia.

A new alkaloid featured with a dibenz[c,e]azepin-5-one scaffold, namely emililactam A (3), together with a known pyrrolidine alkaloid (emilisonchine, 1) and a known flavonoid alkaloid [8-(2″-pyrrolidinone-5″-yl)-quercetin, 2] were isolated from the aerial parts of Emilia sonchifolia. Compounds 1 and 2 were isolated as racemic forms which were further separated, for the first time, to their corresponding enantiomers [(+)-1/(-)-1 and (+)-2/(-)-2], respectively, by using chiral-phase HPLC. The structure of new compound 3 was elucidated by extensive spectroscopic analysis. In addition, the absolute configurations of optically pure (+)-1/(-)-1 and (+)-2/(-)-2 were determined by the time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. In an in vitro bioassay, compounds (+)-1, (-)-1, (±)-1, and 3 exhibited moderate neuroprotective effects against corticosterone-induced injuries of PC12 cells.

The Regulatory Effects of Licochalcone A on the Intestinal Epithelium and Gut Microbiota in Murine Colitis.

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.

Simultaneous Determination and Risk Assessment of Pyrrolizidine Alkaloids in Artemisia capillaris Thunb. by UPLC-MS/MS Together with Chemometrics.

Pyrrolizidine alkaloids (PAs) are natural toxins found in some genera of the family Asteraceae. However, it has not been reported whether PAs are present in the widely used Asteraceae plant Artemisia capillaris Thunb. (A. capillaris). The purpose of this study was to establish a sensitive and rapid UPLC-MS/MS method together with chemometrics analysis for simultaneous determination and risk assessment of PAs in A. capillaris. The developed UPLC-MS/MS method was validated and was confirmed to display desirable high selectivity, precision and accuracy. Risk assessment was conducted according to the European Medicines Agency (EMA) guideline. Chemometrics analysis was performed with hierarchical clustering analysis and principal component analysis to characterize the differences between PAs of A. capillaris. Finally, PAs were found in 29 out of 30 samples and at least two were detected in each sample, besides, more than half of the samples exceeded the EMA baseline. Nevertheless, the chemometrics results suggested that the PAs contents of A. capillaris from different sources varied significantly. The method was successfully applied to the detection and risk evaluation of PAs-containing A. capillaris for the first time. This study should provide a meaningful reference for the rational and safe use of A. capillaris.

Cryptoporic acid S, a new drimane-type sesquiterpene ether of isocitric acid from the fruiting bodies of Cryptoporus volvatus.

A new drimane-type sesquiterpene with an isocitric acid moiety, cryptoporic acid S (1), together with six known compounds, cryptoporic acid D (2), ß-sitosterol (3), ß-daucosterol (4), stigmast-4-en-3-one (5), ergosterol (6), and (22E,24R)-ergosta-7,22-diene-3ß,5α,6ß-triol (7), was isolated from the fruiting bodies of Cryptoporus volvatus. The structures of these compounds were established on the basis of UV, IR, MS, 1D and 2D NMR analysis. In the meanwhile, compounds 1 and 2 were evaluated for antioxidant activity using the methods of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (DPPH-RSA) and ferric reducing antioxidant power (FRAP) assay, and they exhibited moderate antioxidant activities.

An unusual sesquiterpene coumarin from the seeds of Ferula sinkiangensis.

A sesquiterpene coumarin, sinkiangenorin E, consisting of a novel bicyclo[4.3.1]decane-type sesquiterpene system, was isolated from the seeds of Ferula sinkiangensis. The structure of sinkiangenorin E including the relative stereochemistry and the absolute configuration was elucidated on the basis of spectroscopic data. The new compound showed cytotoxic activity against AGS cells (IC50, 12.7 µM) and inhibiting effect against influenza A H1N1 (IC50, 4.0 µM), which provided important clues for the study on the bioactivities of this type of sesquiterpene coumarins.

[Chemical constituents of lateral roots of Aconitum carmichaelii Debx].

In order to find the cardiotonic constituents of lateral roots of Aconitum carmichaelii Debx., the investigation was carried out. Silica gel column chromatography, Sephadex LH-20, medium-pressure MCI and reverse phase ODS column chromatography were used to separate the 90% EtOH extract of the lateral roots of Aconitum carmichaelii Debx. The structures of the isolated compounds have been identified by chemical properties and spectroscopic analyses. Ten compounds were isolated and their structures were elucidated as benzoic acid-5-hydroxy-2-benzoyl-amino methyl ester (1), honokiol (2), pinoresinol (3), salicylic acid (4), p-hydroxy-cinnamic acid (5), songorine (6), karakoline (7), mesaconitine (8), hypaconitine (9) and 14-benzoylhypaconitine (10), separetely. Compound 1 is a new compound and its structure has been established by NMR, HR-ESI-MS, UV, IR and X-Ray. Compound 2-5 are isolated from the lateral roots of Aconitum carmichaelii Debx. for the first time.