Spirocitromycetin, a Fungal Polyketide with an Antiosteoporotic Pharmacophore.

Spirocitromycetin, an antiosteoporotic polyketide bearing a unique spirocycle, was characterized from a human mucus sputum-derived . Its structure and absolute configuration were elucidated spectrally, with its biosynthetic pathway likely mediated via polivione, a reported heptaketide. Spirocitromycetin was shown to be antiosteoporotic at 0.

Holistic quality evaluation of commercial Agastache rugosa by multiple chromatographic and chemometric analysis.

In present study, a comprehensive strategy integrating multiple chromatographic and chemometric methods to simultaneously characterize the volatile and non-volatile components was developed for the holistic quality evaluation of commercial Agastache rugosa (AR), a common edible and medicinal herb, collected in China. The volatile components and the non-volatile components were characterized by GC-MS and UPLC-QTOF-MS/MS, respectively. And the data were analyzed either independently or integratively by multivariate statistical analysis (MVS) for the quality assessment of commercial samples.

[Effect of lupeol on invasion and metastasis of human hepatoma HepG2 and SK-HEP-1 cells and its mechanism].

Epithelial-mesenchymal transformation(EMT) exists in embryonic development and is closely related to cell migration and invasion. The increased EMT level in tumors showed that E-cadherin was replaced by N-cadherin, and the expression of interstitial markers such as α-SMA and vimentin was up-regulated. It has been reported that lupeol can reduce the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9) and N-cadherin to inhibit the metastasis of osteoma cells.

[Acute toxicity mechanism of Panax notoginseng saponins in larvae zebrafish based on metabonomics].

Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways.

Design and synthesis of novel celastrol derivative and its antitumor activity in hepatoma cells and antiangiogenic activity in zebrafish.

Two series of celastrol derivatives were designed and synthesized by modifying carboxylic acid at the 28th position with amino acid, and their intermediates with isobutyrate at the third position. All compounds were evaluated for their antiproliferation activity by four human cancer cell lines (SCG7901, HGC27, HepG2, and Bel7402) and one normal cell LO2. The most promising compound, compound 8, showed superior bioactivity and lower toxicity than others including celastrol.

Citrofulvicin, an Antiosteoporotic Polyketide from Penicillium velutinum.

Citrofulvicin (1), along with its early shunt product fulvionol (2), was characterized as a skeletally unprecedented antiosteoporotic agent from a human sputum-derived fungus Penicillium velutinum. The unique citrofulvicin framework is likely formed by a nonenzymatic intermolecular Diels-Alder cycloaddition between heptaketide-based intermediates. Citrofulvicin and fulvionol were demonstrated to be osteogenic at 0.

Acaulins A and B, Trimeric Macrodiolides from Acaulium sp. H-JQSF.

Acaulin A (1) and its macrolactone ring-opened congener acaulin B (2) were characterized from the culture of Acaulium sp. H-JQSF (an isopod-associated fungus) as architecturally undescribed trimeric macrodiolides, with the former being antiosteoporotic at 0.4 μM in the prednisolone-induced osteoporotic zebrafish.

Metabolism of five diterpenoid lactones from tubers in zebrafish.

Diterpenoid lactones (DLs) have been reported to be the main hepatotoxic constituents in tubers (DBT), a traditional Chinese medicinal herb. The acquisition of early information regarding its metabolism is critical for evaluating the potential hepatotoxicity of DLs. We investigated, for the first time, the main metabolites of diosbulbin A (DIOA), diosbulbin C (DIOC), diosbulbin (DIOG), diosbulbin (DIOM) and diosbulbin (DIOF) in adult zebrafish.

Acaulide, an Osteogenic Macrodiolide from Acaulium sp. H-JQSF, an Isopod-Associated Fungus.

Acaulide (1), a macrodiolide with an unprecedented framework, was characterized along with its shunt products-acaulones A (2) and B (3)-from the culture of Acaulium sp. H-JQSF associated with the isopod Armadillidium vulgare. The spiro-linked 14-, 14-, and 6-membered cycles of 1 arise likely from iterative intermolecular Michael addition reactions.

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo.

[Research and application of hepatotoxicity evaluation technique of traditional Chinese medicine].

The safety of traditional Chinese medicine (TCM) has received the widespread attention in recent years. Hepatotoxicity of TCM is one of the key problems of the safety of TCM. This article summarized research progress and application prospect in the mechanism of TCM hepatotoxicity, biomarkers, toxic omics database, prevention of hepatotoxicity of the liver cell lines, subcellular fraction, three-dimensional cultivation models, the model animals, aiming to provide theoretical basis for TCM toxicity evaluation and technical guidelines, thus promoting the development of TCM toxicity studies.

Rapid identification of herbal compounds derived metabolites using zebrafish larvae as the biotransformation system.

Metabolites derived from herbal compounds are becoming promising sources for discovering new drugs. However, the rapid identification of metabolites from biological matrixes is limited by massive endogenous interference and low abundance of metabolites. Thus, by using zebrafish larvae as the biotransformation system, we herein proposed and validated an integrated strategy for rapid identification of metabolites derived from herbal compounds.

Absence of myocyte regeneration by mobilization of bone marrow stem cells after myocardial infarction.

The study aimed to test the potential for bone marrow stem cells (BMSC) mobilized by granulocyte macrophage colony stimulating factor (GM-CSF) to promote neovascularization and cardiomyocytes regeneration in a rat model of myocardial infarction. The myocardial infracted rats were randomly assigned to receive GM-CSF injection as GM-CSF group or received saline injection as control group. Evaluation of CD34 stem cells was performed by flow cytometry.

Biotransformation of ginsenosides F and Rg in zebrafish.

Ginsenosides F and Rg (GF and GRg), two main active components of steamed notoginseng or red ginseng, are dehydrated disaccharide saponins. In this work, biotransformation of ginsenosides F and Rg in zebrafish was investigated by qualitatively identifying their metabolites and then proposing their possible metabolic pathways. The prediction of possible metabolism of ginsenosides F and Rg using zebrafish model which can effectively simulate existing mammals model was early and quickly performed.

Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine.

Purpose: Hepatocellular carcinoma (HCC) cases are closely associated with chronic inflammation and fibrosis which is known as hepatic inflammation-fibrosis-cancer (IFC) axis. The aim of this study is to elucidate the development characteristics of the rat HCC model based on IFC axis.

Methods: The diethylnitrosamine (DEN)-induced rat HCC, which presents a stepwise histopathological progression that is similar to human HCC, was used to analyze the features of the different stages (inflammation, fibrosis, cancer).

Gualou Xiebai decoction inhibits cardiac dysfunction and inflammation in cardiac fibrosis rats.

Background: Gualou Xiebai Decoction (GXD) is a well-known traditional Chinese recipe. It has been used to treat cardiovascular disorders for nearly two thousand years. But there is a lack of reports on cardiac fibrosis and underlying mechanism.

[Screening on antiosteoporotic active parts of dipsacus radix based on zebrafish model].

Objective: Prednisolone-induced osteoporosis model using zebrafish was used to screen the antiosteoporotic active parts of Dipsacus Radix, in order to investigate the applicability and rationality of the zebrafish model of osteoporosis.

Methods: Zebrafish larvae at 5 days post fertilization (dpf) were exposed with 25 micromol/L prednisolone and 0.5% DMSO for 48 h, then except one group of 25 micromol/L prednisolone, other groups of 25 micromol/L prednisolone were treated with a range of concentration (0.

[Two-dimensional zebrafish model combined with hyphenated chromatographic techniques for evaluation anti-osteoporosis activity of epimendin A and its metabolite baohuoside I].

This article firstly established a new efficient method for screening anti-osteoporosis ingredients, which used two-dimensional zebrafish model combined with hyphenated chromatographic techniques to evaluate anti-osteoporosis activities of epimedin A and its metabolite baohuoside I. Adult zebrafish was used for metabolism of epimedin A in 0.5% DMSO, and LC-MS was used for analysis of the metabolite, which was captured by HPLC, and prednisolone-induced osteoporosis model of zebrafish was used to evaluate the anti-osteoporotic activities of trace amounts of epimedin A and baohuoside I.

[Ideas and methods of two-dimensional zebrafish model combined with chromatographic techniques in high-throughput screening of active anti-osteoporosis components of traditional Chinese medicines].

Objective: To break through the restrictions of the evaluation model and the quantity of compounds by using the two-dimensional zebrafish model combined with chromatographic techniques, and establish a new method for the high-throughput screening of active anti-osteoporosis components.

Method: According to the research group-related studies and relevant foreign literatures, on the basis of the fact that the zebrafish osteoporosis model could efficiently evaluate the activity, the zebrafish metabolism model could efficiently enrich metabolites and the chromatographic techniques could efficiently separate and analyze components of traditional Chinese medicines, we proposed that the inherent combination of the three methods is expected to efficiently decode in vivo and in vitro efficacious anti-osteoporosis materials of traditional Chinese medicines.

Result And Conclusion: The method makes it simple and efficient in the enrichment, separation and analysis on components of traditional Chinese medicines, particularly micro-components and metabolites and the screening anti-osteoporosis activity, fully reflects that efficacious materials of traditional Chinese medicines contain original components and metabolites, with characteristic of "multi-components, multi-targets and integral effect", which provides new ideas and methods for the early and rapid discovery of active anti-osteoporosis components of traditional Chinese medicines.

[Processing mechanism of Epimedium fried with suet oil based on absorption and metabolism of flavonoids].

As beneficial traditional Chinese medicine, Epimedium fried with suet oil can enhance the effect of warming kidney yang. Previous literature studies about processing of Epimedium mainly focused on changes in chemical composition and pharmacological effect. From the angle of flavonoids absorption and metabolism, our group innovatively study the processing mechanism of Epimedium based on active component transformation combined with intestinal absorption barrier.

[Construction of research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier].

Based on practice of Epimedium processing mechanism for many years and integrated multidisciplinary theory and technology, this paper initially constructs the research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier, which to form an innovative research mode of the " chemical composition changes-biological transformation-metabolism in vitro and in vivo-intestinal absorption-pharmacokinetic combined pharmacodynamic-pharmacodynamic mechanism". Combined with specific examples of Epimedium and other Chinese herbal medicine processing mechanism, this paper also discusses the academic thoughts, research methods and key technologies of this research system, which will be conducive to systematically reveal the modem scientific connotation of traditional Chinese medicine processing, and enrich the theory of Chinese herbal medicine processing.

Characterization of metabolites of 20(S)-protopanaxadiol in rats using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry.

In this study, ultra-performance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (QTOF-MS) was applied to the rapid analysis of 20(S)-protopanaxadiol (PPD) metabolites in rats after oral administration, enabling the structural characterization of 23 metabolites in plasma, bile, urine, and feces. 16 of these, including M1-M5, M9, and M11-M15, have not been previously reported. The results also indicated that demethylation, dehydration, dehydrogenation, oxidation, deoxidation, and glucuronidation were the major metabolic reactions of PPD in vivo.

[Metabolism study of asperosaponin VI by using zebrafish].

Model organism zebrafish was used to study metabolism of asperosaponin VI from Dipsacus asper Wall. ex Henry for the first time. Metabolic components of asperosaponin VI after exposing to zebrafish for 24 h were identified by high performance liquid chromatography--electrospray mass spectrometry (HPLC-ESI-MS), the separation was performed with a Zorbax C18 column using a binary gradient elution of 0.

[Establishment of zebrafish osteopenia model induced by dexamethasone].

Zebrafish was selected as model animal, and glucocorticoid dexamethasone was used as a model compound to establish a rapid and high efficient osteopenia model. Zebrafish larvae at 4 days post fertilization (dpf) were exposed to a serial concentrations of dexamethasone solutions, and 0.5% DMSO was selected as the vehicle control group.

Enhancement of epimedium fried with suet oil based on in vivo formation of self-assembled flavonoid compound nanomicelles.

The purpose of this work was to research the enhancement of Epimedium fried with suet oil based on the in vivo formation self-assembled flavonoid nanomicelles. Taking icariin as the representative, under the action of suet oil, self-assembled nanomicelles were prepared under simulated gastrointestinal tract conditions and were characterized by dynamic light scattering and transmission electron microscopy (TEM). The experiments with icariin self-assembled nanomicelles without suet oil were done according to the above.