Anti-anaphylactic potential of benzoylpaeoniflorin through inhibiting HDC and MAPKs from Paeonia lactiflora.

Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of ß-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.

Bioactivity-Guided Discovery of Human Carboxylesterase Inhibitors from the Roots of Paeonia lactiflora.

In a continuing search for potential inhibitors against human carboxylesterases 1A1 and 2A1 (hCES1A1 and hCES2A1), an EtOAc extract of the roots of Paeonia lactiflora showed strong hCES inhibition activity. Bioassay-guided fractionation led to the isolation of 26 terpenoids including 12 new ones (1-5, 7-12, and 26). Among these, sesquiterpenoids 1 and 6, monoterpenoids 10, 11, and 13-15, and triterpenoids 18-20, 22, and 24-26 contributed to the hCES2A1 inhibition, in the IC50 range of 1.9-14.5 µM, while the pentacyclic triterpenoids 18-26 were responsible for the potent inhibitory activity against hCES1A1, with IC50 values less than 5.0 µM. The structures of all the compounds were elucidated using MS and 1D and 2D NMR data, and the absolute configurations of the new compounds were resolved via specific rotation, experimental and calculated ECD spectra, and single-crystal X-ray diffraction analysis. The structure-activity relationship analysis highlighted that the free HO-3 group in the pentacyclic triterpenoids is crucial for their potent inhibitory activity against hCES1A1.

[A new lignan glucoside from root of Paeonia lactiflora].

A new lignan glucoside,(+)-fragransin A_2-4-O-ß-D-glucopyranoside(1), has been isolated from the dry root of Paeonia lactiflora by column chromatography on silica gel, Sephadex LH-20, and MCI-gel resin, as well as preparative RP-HPLC. The structure of the new compound was elucidated by spectroscopic data analysis(MS, UV, IR, CD, 1 D and 2 D NMR) and chemical method. Compound 1 showed moderate inhibition against lipopolysaccharide induced nitric oxide production in RAW264.7 macrophages, with an IC_(50) value of 21.3 µmol·L~(-1).

Yanhusanines A-F, Isoquinoline-Derived Alkaloid Enantiomers from Corydalis yanhusuo and Their Biological Activity.

Six new pairs of isoquinoline alkaloid enantiomers, designated as yanhusanines A-F (1-6), were isolated from an aqueous extract of Corydalis yanhusuo tubers. The structures of these enantiomers were elucidated via physicochemical analysis and a variety of spectroscopic methods. All compounds were resolved into their enantiomers via chiral-phase HPLC, and their configurations were determined by DP4+ NMR calculation methods, specific rotations, and comparison of experimental and calculated ECD spectra. Compounds 1-6 bear a rare 9-methyl moiety, and compound 1 possesses a rare 1-oxa-6-azaspiro[4.5]decane core containing an N-CHO group. Compounds (+)-2, (-)-2, (+)-4, (-)-4, (+)-5, (-)-5, (+)-6, and (-)-6 exhibited selective inhibitory activities against human carboxylesterase (hCE2), in the IC50 value range of 2.0-13.2 µM.

The Prognosis Of Peroxiredoxin Family In Breast Cancer.

PURPOSE: PRDX (Peroxiredoxin) family has involved in breast cancer tumorigenesis from the evidence obtained from cell lines, human tissues and mouse models. Nonetheless, the diversified expression patterns, coupled with the prognostic values of PRDX family, still require explanation. This study aimed at investigating the clinical importance and biological of PRDXs in breast cancer. PATIENTS AND METHODS: Specimens of paraffin sections used for immunohistochemistry were collected from the hospital and the remaining patient information was retrieved from online databases. The expression and survival data of PRDXs in patients with breast cancer were from ONCOMINE, GEPIA, Kaplan-Meier Plotter. cBioPortal, Metascape, String, Cytoscape and DAVID were used to predict functions and pathways of the changes in PRDXs and their frequently altered neighbor genes. Immunohistochemistry was used to detect the expression of PRDXs in breast cancer. RESULTS: We discovered the expression levels of PRDX1-5 were higher in breast cancer tissues than in normal tissues, whereas the expression level of PRDX6 was observed as lower in the former one in comparison with that of the latter one. There existed a correlation between the expression levels of PRDX4, 5 and the advanced tumor stage. Survival analysis revealed that the expression of PRDXs were all associated with relapse-free survival (RFS) in all of the patients with breast cancer. Eventually, we discovered significant regulation of the cellular oxidant detoxification and detoxification of ROS by the PRDX changes, together with obtaining the core modules of genes (TXN, TXN2, TXNRD1, TXNRD2, GPX1 and GPX2) linked to the PRDX family of genes in breast cancer. CONCLUSION: The PRDX family is widely involved in the development of breast cancer and affects the prognosis of patients. The functions and pathways of the changes in PRDXs and their frequently altered neighbor genes can be further verified by wet experiments.

[Study on structural conversion of dihydrochelerythrine in different solvents].

Dihydrochelerythrine was isolated from the ethanol extract of Corydalis yanhusuo by chromatographic and recrystallization techniques. To our knowledge, this is the first report that dihydrochelerythrine was found to be unstable. The NMR, HPLC, and LC-MS were applied to monitor the structural conversion process of dihydrochelerythrine. The results showed that when dissolved in polar deuteration solvent (e.g., DMSO-d6 & MeOD), dihydrochelerythrine is directly converted to chelerythrine gradually. However, if used non-polar reagent (e.g.,CD2Cl2), the sample of dihydrochelerythrine undergoes the formation of pseudobase, chelerythrine, and bimolecular ether then followed by oxidation to oxychelerythrine as the major final product. Which leads to this phenomenon maybe is that the C-6 in dihydrochelerythrine is highly reactive to nucleophiles, and is easily converted to different derivatives in different solvents attributed to the solvent effect. This finding will contribute to the extraction and isolation, bioactivity screening, and quality evaluation of medicinal materials containing dihydrochelerythrine and other similar derivatives.