Resveratrol possesses a wide range of biological activities, such as anti-cancer, anti-oxidation, induction of apoptosis, etc., but its poor drug properties, rapid metabolism, low target selectivity and bioavailability limit its application value. Studies have shown that modification of the structure of natural compounds can improve their pharmacological activities. To improve the bioavailability of resveratrol, many researchers have undertaken the synthesis and activity evaluation of resveratrol derivatives and analogues. They have modified the phenolic hydroxyl groups, double bonds and benzene ring of resveratrol so as to further understand the interactions among functional groups and its structure-activity relationship. In this paper, we review the chemical structures, synthetic methods and mechanisms of biological activity of resveratrol monomer derivatives as well as their related therapeutic applications, especially in the anticancer area over the last decade. This will provide some reference value for the further research and development of resveratrol-related drugs.

Philadelphia chromosome (Ph) positive (Ph⁺) B cell acute lymphoblastic leukemia (B-ALL) is the most common genetic abnormality associated with B-ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that high tribbles homologue 3 (TRIB3) expression contributes to multi-cancer development and progression, but the underlying role and molecular mechanisms of TRIB3 in Ph⁺ B-ALL remain unclear. Here, we report that TRIB3 expression was enhanced in Ph⁺ B-ALL patient samples and positively associated with the expression of breakpoint cluster region-Abelson tyrosine kinase (BCR-ABL). We further demonstrated that deletion of TRIB3 attenuated the progression of Ph⁺ B-ALL by reducing BCR-ABL expression. Mechanistically, TRIB3 interacted with lysosomal cysteine proteinase cathepsin Z (CTSZ) to suppress CTSZ-mediated BCR-ABL degradation, which enhanced BCR-ABL activity, causing high proliferation of Ph⁺ B-ALL cells. Thus, our study indicated that inhibiting the expression of TRIB3 to regulate BCR-ABL kinase activity may be exploited as an additional target therapy for Ph⁺ ALL. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College. The procedure of human leukemia sample was approved by the Ethics Committee of Chinese Academy of Medical Sciences and Peking Union Medical College (KT2019055-EC-1).

In this study, the effect of benzo[α]pyrene (BaP) on chaperone-mediated autophagy (CMA) in a simulated hypoxia environment was observed and the relationship to heat shock protein 90 (HSP90) was clarified. With HSP90 inhibitor geldanamycin (GA) and HSP90α silenced, the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), HSP90, heat shock cognate protein 70 (HSC70), and lysosomal associated protein 2A (LAMP-2A) of A549 cells on hypoxic environment by BaP were tested. Alkaline comet experiment, immunofluorescence γ-H2AX focus experiment, quantitative real-time PCR (qPCR), and Western blot analyses were used to clarify the relationship between the DNA damage of different concentrations of BaP in A549 cells and the mRNA and protein expression of CMA-related factors. The results show that hypoxia can promote the expression of mRNA and protein of CMA-related factors in A549 cells. This study found that BaP has an inhibitory effect on CMA under the hypoxic environment. The inhibition or silencing of HSP90 will enhance the inhibitory effect of BaP on CMA. In a normoxic environment, BaP causes DNA damage and promotes CMA.

Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg^-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg^-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.

Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis (AS) were identified by network pharmacology and molecular docking analyses. The Traditional Chinese Medicine Database (TCMD) and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to identify the likely active components of Polygonati rhizoma. The potential targets set of Polygonati rhizoma were predicted with the PharmaDB database and the Swiss TargetPrediction database. The targets set for AS was retrieved by OMIM, DisGeNET and NCBI Gene database. We used the STRING platform to construct a protein-protein interaction network of the intersectional targets and performed visual analysis in Cytoscape. The key targets of Polygonati rhizoma in AS were searched by network topology and the resulting GO and KEGG enrichment was analyzed by Clue GO. In addition, the key targets were verified by molecular docking in Discovery Studio 4.0. A total of 45 active ingredients and 51 potential targets were obtained in the treatment of AS. The results of the topology analysis included five key targets:serum albumin, mitogen-activated protein kinase 3, mitogen-activated protein kinase 1, proto-oncogene tyrosine-protein kinase Src and matrix metalloproteinase-9. The 131 GO items showed that the biological process mainly involved the steroid receptor, cell response to steroid stimulation, the phosphatidylinositol-3 kinase signal pathway, and others. The KEGG pathway analysis included 37 pathways, which were closely related to peroxisome proliferation activated receptor signaling pathway, platelet activation pathway, vascular endothelial growth factor pathway, hypoxia inducible factor pathway and adhesion connection pathway. The results of molecular docking proved that the combined activity of the components with potential key targets is excellent. This study proposes mechanisms by which Polygonati rhizoma might act to reverse or minimize AS and provides a scientific basis for clinical research on Polygonati rhizoma.

Peptidyl-prolyl cis-trans isomerase Pin1 is over-expressed in prostate cancer cells and the level of expression correlates with the malignancy grade and prognosis in patients. In this work, twenty-one 2-(1H-benzimidazol-2-ylthio) acetic acid derivatives were designed and prepared with the aid of the crystal structure of Pin1 and our previous work. The chemical structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR, ESI-MS and IR. The inhibitory activity of compounds 6a-6i and 13a-13i against Pin1 were determined using a protease-coupled assay. The results indicated that twenty compounds were significantly superior to the positive control drug Juglone, and 6g, 6h and 13i exhibited the most potent Pin1 inhibitory activity, with IC₅₀ values at the sub-micromolar level. The in vitro anti-proliferative activities of these analogs were evaluated by the MTT assay and several showed a moderate effect in human prostate cancer PC-3 cells. Molecular docking studies demonstrated that both the benzimidazole skeleton and the thioacetic acid fragment were indispensable for the compounds to interact with key residues in the catalytic domain of Pin1.

We used network pharmacology and molecular docking to investigate the molecular mechanism of Lishi-Kuijie decoction (KJF) in the treatment of ulcerative colitis (UC). Chemical components and targets related to the 13 herbs of Chinese Materia Medical in KJF were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UC-related targets were identified through OMIM, DisGeNet and GeneCards databases. Using Cytoscape 3.7.2 software a drug-compound-disease-target network was established. The target interaction network and core target for KJF against UC was built and selected based on the String database and topological parameters. Using the R package clusterprofile in Bioconductor, the intersection genes and the disease-drug intersection targets were transformed to Entrez gene ID, followed by gene ontology biological process enrichment analysis and KEGG pathway annotation analysis. The KJF compound-UC target network contained 149 compounds, 108 corresponding targets and 12 core targets (including signal transducer and activator of transcription 3, interleukin 6, tumor necrosis factor, c-x-c motif chemokine ligand 8, interleukin 2, etc.). We identified 2 371 GO terms and 155 pathways (mainly involving IBD, PI3K-ATK, NF-kappa B, TNF, Toll-like receptor signaling pathway) as determined by enrichment analysis. Molecular docking, used with the key molecular factors and the core targets, revealed stable binding for IL2, TNF-α, MAPK1 and RELA. These results suggest the possible molecular mechanism of KJF in treatment of UC and lay the foundation for further characterization of the components and their mechanisms.

The glycosylation heterogeneity of recombinant human pro-urokinase (pro-UK) was assessed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Firstly, the source of heterogeneity was determined by measuring the M_r of intact protein before and after N-deglycosylation. Glycosylation sites and the proportion of O-glycopeptides then were determined at the peptide level. Finally, the N-glycans were confirmed and quantified using the N-glycan profile. Results show that the structural heterogeneity of pro-UK is mainly caused by glycosylation. All T₁₈ were fucosylated, and 6.4% of S_138/139 was O-glycosylated with two kinds of oligosaccharides with a ratio of 6.0% and 0.4% respectively. All N₃₀₂ positions were N-glycosylated by more than ten types of glycans, among which A2F and A3F accounted for 80% of the total. The assessment of glycosylation heterogeneity of pro-UK will provide a reference for quality standardization.

The effects of alcohol extracts from roots, stems, leaves, and flowers of Scutellaria Baicalensis Georgi (SBG) on endogenous metabolism in D-gal-induced aging-model rats were investigated by ¹H NMR metabolomics. Results showed that 32 endogenous metabolites were identified in the urine. Combined with the VIP value and t-test, 14 different metabolites were found by multivariate statistical analysis of the spectrum. Compared with the control group, the content of α-ketoglutaric acid, hippuric acid and 3-hydroxybutyrate in the urine of rats in the model group was significantly decreased (P < 0.05) and the content of trimethylamine oxide, glycine, alanine, lactic acid, dimethylglycine, acetate, pyruvate, taurine, allantoin, betaine, N-acetylated glycoprotein was significantly increased (P < 0.05). The metabolites were mainly derived from taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; pyruvate metabolism; glycolysis/gluconeogenesis; glyoxylic acid and dicarboxylic acid metabolism; and the tricarboxylic acid cycle. The content of differential metabolites in urine samples was altered by the alcohol extracts from the different parts of SBG. Leaves extracts of SBG had the greatest effect on urine metabolites, and mainly affected taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; and pyruvate metabolism. This study provides a reliable experimental basis for the future development of SBG. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036).

This paper aimed to study the effect of combined co-processing of coating and pore forming on the tableting and tablet properties of traditional Chinese medicine (TCM) extracts together with its applicability. Four TCM extracts were co-processed using fluid bed with hydroxypropyl methyl cellulose (HPMC) as coating agent and ammonium bicarbonate (NH₄HCO₃) as pore-forming agent. Powder properties (such as particle size and size distribution, bulk density, tap density, moisture content) and tablet properties (including tensile strength, compaction ratio, fast elastic stretch, and disintegration time) were measured and compared among the powders. Scanning electron microscopy (SEM) was applied to characterize the surface of particles and tablets. Results showed that the particle size, flowability, and compactibility of the composite particles with HPMC were superior to the parent powders of TCM extracts. These properties of the porous particles with HPMC and NH₄HCO₃ showed further improvements. In addition, the addition of HPMC prolonged the disintegration time of tablets, whereas the pore-forming effect of NH₄HCO₃ could shorten the disintegration time. SEM revealed the changes in the morphology of the composite particles and the pores on the surface of the porous particles and tablets. In conclusion, co-processing with HPMC and NH₄HCO₃ could improve the powder and tablet properties of TCM extract powders, and this method shows certain applicability, which provides a feasible choice for improving the tableting properties of some TCM extract powders.