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Three undescribed sesquiterpenoids, phaeocaulisguatriol (1) and phaeocaulistriol A-B (19, 20), along with twenty known sesquiterpenoids were isolated from a chloroform-soluble extract of Curcuma phaeocaulis Valeton rhizome. Their structures were determined using comprehensive spectroscopic methods. All isolated compounds were evaluated for their cytotoxicity against five human tumor cell lines Hela, HepG2, MCF-7, BGC823, and A549. Among them, phaeocaulisguatriol (1) and phaeocaulistriol B (20) showed potent cytotoxic activity against MCF-7 (IC50 of 40.7 and 58.8 μM, respectively), by inducing apoptosis. The effectiveness of compounds 1 and 20 was supported by predictive intermolecular interactions in molecular docking. Molecular dynamics simulation studies further probed the interaction mechanism under simulated physiological conditions between the two most active compounds and the TP53 protein, an apoptotic effector protein. Moreover, Western blot experiments confirmed that compound 1 induces apoptosis by activating the expression of TP53 and caspase 3 proteins. This work provides a deep insight into new sesquiterpenoids isolated from C. phaeocaulis Valeton acting as potential antitumor activity inhibitors. [ABSTRACT FROM AUTHOR]

Currently, extraction process optimization is generally based on a few features, regardless of their different changing trends and the panoramic view of the extraction process. Comprehensive evaluation and understanding is hard to establish due to the small number of experiments. Here, machine learning-assisted optimization is demonstrated for better understanding the complex extraction process based on data from an orthogonal experimental design (OED). From two perspectives of panoramic characteristics and specific characteristics, several observations are adopted to evaluate the performance of the extraction process, including quantitative 1H NMR, HPLC fingerprint, molecular weight, yield of dry extract and content of components. The close relationship between influencing factors and the extraction performance is described by grey relation analysis. With the help of radial basis function neural network (RBFNN), a nonlinear fitting regression equation is developed for every observation and influencing factor. A genetic algorithm is then introduced for multi-objective optimization and Pareto fronts are obtained. To select the best combination of water extraction process and ethanol extraction process, a list of the combinations of Pareto front points from those extraction processes is formed and ranked using CRITIC-TOPSIS. Finally, the ideal extraction is characterized by molecular weight, monosaccharide composition and UHPLC-MS/MS. With the verification between OED experiments and machine learning, the changing rates of all observations range from 1.33% to 30.11%, which confirms that machine learning-assisted optimization gives better performance than conventional OED. Molecular weight could range from 61.5~594.9 kDa with some are over measuring range, furthermore mannose and glucose are the most abuntant monosaccharides of the polysaccharide from ideal extraction. 160 components are identified via UHPLC-MS/MS as well. In conclusion, ML is a powerful tool for predicting and understanding extraction processes, thus accelerating the development of eco-friendly extraction processes. [ABSTRACT FROM AUTHOR]

Esculentoside A (EsA) is a kind of triterpenoid saponins from the root tuber of Phytolacca acinosa Roxb. It has extensive medicinal activity, such as antibacterial, anti‐inflammatory, immune regulation, and cell proliferation inhibition. However, some researches suggested that EsA can cause hepatotoxicity, whose mechanism is not precise. To ensure the safety and reliability in the clinical use of Phytolacca acinosa Roxb., it is necessary to establish a rapid and accurate method to evaluate the toxicity, analyze and verify the toxicity mechanism of EsA. Therefore, this research explored the mechanism of hepatotoxicity induced by EsA in rats and analyzed endogenous metabolites' changes in rat plasma by combining network toxicology with non‐targeted metabolomics. We obtained 58 critical targets of EsA induced hepatotoxicity in rats based on the strategy of network toxicology, including albumin, mitogen‐activated protein kinase 1, Caspase‐3, etc. Many important pathways were obtained by Kyoto Encyclopedia of Genes and Genomes enrichment analysis, such as HIF‐1 signaling pathway, TNF signaling pathway, IL‐17 signaling pathway, and other concerning pathways. Sixteen biomarkers, including 5‐hydroxykynurenamine, N‐acetylserotonin, palmitic acid, etc., were screened from rat plasma using Ultra‐performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC‐Q‐TOF/MS), mainly involve Glycerophospholipid metabolism, Tryptophan metabolism, and other metabolic pathways. Further analysis showed that EsA may induce liver injury by activating oxidative stress and energy metabolism disorders, triggering inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Nanoparticles modified with aminopropyl group were prepared by a single-step electrospray process and used as a pseudo-stationary phase for the separation of anions, (e.g., organic acids in capillary electrophoresis). The nanoparticles form a uniform suspension which is stable in a buffer without adding other stabilizer. The amino containing nanoparticles have significant impact on the electro-osmotic flow (EOF) of the system, which, in turn, affects the overall separation of other analytes in this system. For example, five organic acids, which were not all separable in zone electrophoresis, were fully resolved in the presence of the nanoparticles in a wide range of pH. Various experimental parameters that are related to the electrophoresis including EOF, pH, organic modifier, voltage, concentration of the running buffer and concentration of the nanoparticles have been investigated. The repeatability of the migration time and peak area in this system are better than 5% for both inter- and intra-day evaluation. [ABSTRACT FROM AUTHOR]

A chiral complex, SalenZn(II) (S), was synthesized and characterized. Its coordination with imidazole derivatives and amino acid ester derivatives was studied by UV-vis spectrophotometric titrations and CD spectroscopy. The binding constants decreased in the order K (Im)> K (2-MeIm)> K (2-Et-4-MeIm)> K (N-MeIm) for imidazole derivatives, and K (AlaOMe)> K (PheOMe)> K (ValOMe) for amino acid ester derivatives with the same configuration and K D > K L for amino acid esters with different configuration. CD spectra can quantify the strength of SalenZn(II)-ligand interactions, giving results consistent with the magnitudes of the binding constants. Moreover the minimum energy conformations of the adducts were obtained by simulated annealing, and quantum chemical calculations were performed based on those conformations to explain experimental results at the molecular level. [ABSTRACT FROM AUTHOR]

Background: Yuquan Pill (YQW) is a modern concentrated pill preparation of six herbs, namely, Ge Gen ( Pueraria lobata Ohwi), Di huang ( Rehmannia glutinosa Libosch.), Tian Huafen ( Trichosanthes kirilowii Maxim.), Mai Dong ( Ophiopogon japonicus (L. f.) Ker Gawl.), Wu Weizi ( Schisandra chinensis (Turcz.) Baill.) and Gan Cao ( Glycyrrhiza uralensis Fisch.). It is extensively used to treat type 2 diabetes-related glucose and lipid metabolism disorders. But what's the pharmacodynamic substance and how it works in the treatment of Type 2 diabetes mellitus (T2DM) are still unclear. Purpose: The purpose of this study is to determine the likely pharmacological components and molecular mechanism of YQW's intervention on T2DM by combining serum pharmacochemistry, network analysis and transcriptomics. Methods: The efficacy and prototypical components of blood entry were determined after oral administration of YQW aqueous solution to T2DM rats induced by high-fat feed and low-dose streptozotocin (STZ), and the key targets and pathways for these compounds to intervene in T2DM rats were predicted and integrated using network analysis and transcriptomics techniques. Results: In diabetic rats, YQW can lower TG, CHO, NO, and MDA levels ( p < 0.05) while increasing HDL-C levels ( p < 0.01), and protecting the liver and kidney. 22 prototype components (including puerarin, daidzein, 3'-methoxypuerarin, and liquiritigenin, among others) were found in the serum of rats after oral administration of YQW for 90 min, which might be used as a possible important ingredient for YQW to intervene in T2DM rats. 538 YQW pharmacodynamic components-related targets and 1,667 disease-related targets were projected through the PharmMapper database, with 217 common targets between the two, all of which were engaged in regulating PI3K-Akt, MAPK, Ras and FoxO signal pathway. Finally, the mRNA expression profiles of liver tissues from rats in the control, model, and YQW groups were investigated using high-throughput mRNA sequencing technology. YQW can regulate the abnormal expression of 89 differential genes in a disease state, including 28 genes with abnormally high expression and 61 genes with abnormally low expression. Five common genes (Kit, Ppard, Ppara, Fabp4, and Tymp) and two extensively used regulatory pathways (PI3K-Akt and MAPK signaling pathways) were revealed by the integrated transcriptomics and network analysis study. Conclusion: The mechanism of YQW's intervention in T2DM rats could be linked to 22 important components like puerarin, daidzein, and glycyrrhetinic acid further activating PI3K-Akt and MAPK signaling pathways by regulating key targets Kit, Ppard, Ppara, Fabp4, and Tymp, and thus improving lipid metabolism disorder, oxidative stress, and inflammation levels in T2DM rats. On the topic, more research into the pharmacological ingredient foundation and mechanism of YQW intervention in T2DM rats can be done., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lei, Huang, Xie, Wang, Li, Hua, Liu and Yuan.)

Introduction: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease. Recently, growing evidence demonstrates that gut microbiota (GM) plays an important role in RA. But so far, no bibliometric studies pertaining to GM in RA have ever been published. This study attempts to depict the knowledge framework in this field from a holistic and systematic perspective based on the bibliometric analysis., Methods: Literature related to the involvement of GM in RA was searched and picked from the Web of Science Core Collection (WOSCC) database. The annual output, cooperation, hotspots, research status and development trend of this field were analyzed by bibliometric software (VOSviewer and Bibliometricx)., Results: 255 original research articles and 204 reviews were included in the analysis. The articles in this field that can be retrieved in WOSCC were first published in 2004 and increased year by year since then. 2013 is a growth explosion point. China and the United States are the countries with the most contributions, and Harvard University is the affiliation with the most output. Frontiers in Immunology (total citations = 603) is the journal with the most publications and the fastest growth rate. eLife is the journal with the most citations (total citations = 1248). Scher, Jose U. and Taneja, Veena are the most productive and cited authors. The research in this field is mainly distributed in the evidence, mechanism and practical application of GM participating in RA through the analysis of keywords and documents. There is sufficient evidence to prove the close relationship between GM and RA, which lays the foundation for this field. This extended two colorful and tender branches of mechanism research and application exploration, which have made some achievements but still have broad exploration space. Recently, the keywords "metabolites", "metabolomics", "acid", "b cells", "balance", "treg cells", "probiotic supplementation" appeared most frequently, which tells us that research on the mechanism of GM participating in RA and exploration of its application are the hotspots in recent years., Discussion: Taken together, these results provide a data-based and objective introduction to the GM participating in RA, giving readers a valuable reference to help guide future research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Yao, Deng, Li, He, Ren, Zheng, Song, Zhong, Ma, Shan, Lv, Wang, Yuan and She.)

Objective: Curcumae Rhizoma - Sparganii Rhizoma (CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Method: The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MS n . The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model in vivo for the first time and detected by the HepG2 cell model in vitro . Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer. Results: In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs in vitro and in vivo , and the order of activity was CR-SR > CR > SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP). Conclusion: Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Wang, Dong, Zhong, Ren, Song, Ma, Yu, Fan, Yao, Shan, Lv, Zheng, Deng, Li, He, Fan, Zhao, Wang, Yuan and She.)

The preparation of thrombin affinity chromatography media is described in this paper. First, the thrombin affinity chromatography media was prepared through thrombin coupled with cyanogen bromide activated agarose. And then the enzyme activity of thrombin on the coupled media was measured by chromogenic substrate method. The conditions were confirmed based on the enzyme activity of thrombin on the coupled media. The optimum conditions were as follows: the use of Na2CO3-NaHCO3 (containing 0.5 mol/L NaCl) solution of pH 8.3 as the reaction solution, 200 U thrombin per 1 g agarose, and reaction for 10 h at room temperature. The prepared affinity chromatography media had good stability, on which 70.6% of the enzyme activity of thrombin existed after 40 days' storage. The thrombin affinity chromatography media can be widely applied in the screening and purification of thrombin inhibitors in natural products.

As the most popular chiral selectors, β-cyclodextrin (β-CD) and its derivatives have been widely used in enantiomer separations. Among functionalized β-CDs, sulfated β-CDs are recognized as the most effective chiral additives in capillary electrophoresis (CE) separations. Herein, we describe the preparation of a novel sulfated poly β-CD-modified silica-based monolithic column and its use for the enantioseparation of some chiral compounds in the capillary electrochromatography (CEC) mode.

A silica-based CEC monolithic column with mixed modes of RP and weak anion-exchange (WAX) was successfully prepared by using the sol-gel technique at mild temperature. The synthesizing procedure was optimized by changing the ratios of tetraethoxysilane (TEOS), aminopropyltriethoxysilane (APTES), and octyltriethoxysilane (C(8)-TEOS) in the mixture. While serving as WAX group, the amino group dominated the charge on the surface of the capillary column and generated an EOF from cathode to anode at low pH. At pH above 7.5, a cathodic EOF was observed due to the full ionization of silanol group and the suppression in the ionization of amino group. The morphology of monolithic columns was examined by SEM, and the performance of column was evaluated in detail by separating different kinds of compounds. As expected, the monolithic column exhibited RP chromatographic behavior for neutral solutes. Fast and efficient separation of six aromatic acids was obtained using acidic mobile phase with column efficiency up to 160,000 plates/m. Symmetrical peaks can be obtained for aromatic amines because positively charged amino groups on the surface can effectively minimize the adsorption of positively charged analytes to the stationary phase.