Latest ArticlesThe aim of this study was to analyze the anti-cancer effect and mechanism of action of the flavonoids of Astragalus membranaceus (TFA) when combined with cisplatin on Lewis lung carcinoma-bearing mice. This animal experiment was approved by the Committee of the Ethics of Animal Experiment of Shanxi University (SXULL2018012). Pharmacological indices such as tumor weight, tumor volume growth curves, inhibition rate and organ indices showed that the TFA could reduce toxicity and enhance the efficacy of cisplatin. The target of TFA was predicted by network pharmacology analysis and the result showed that calycosin-7-O-β-D-glucoside might be the main active compound responsible for the anticancer effect of TFA. TRP53 (cellular tumor antigen p53), RAC1 (Ras-related C3 botulinum toxin substrate 1), ERBB2 (receptor tyrosine-protein kinase erbB-2), VEGFA (vascular endothelial growth factor A) and STAT3 (signal transducer and activator of transcription 3) may be associated with TFA in enhancing efficacy and reducing the toxicity of cisplatin. The IL-6 content in serum and expression levels of STAT3 and p53 in tumor tissues suggested that TFA may inhibit tumor growth through the IL-6/STAT3 pathway; UPLC-MS-based serum metabolomic analysis suggested that the metabolic pathways related to lung cancer include sphingolipid metabolism, retinol metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, and the TFA-regulated corresponding pathway of bile acid biosynthesis. In this study, the anti-cancer effect and mechanism of action of TFA combined with cisplatin on Lewis lung carcinoma-bearing mice was analyzed by the combination of various techniques, which lay a foundation for further development of anticancer drugs.
Dendrobium moniliforme is an important source of Dendrobii Caulis and one of the main sources of authentic Fengdou. The complete chloroplast genome of D. moniliforme was sequenced using Illumina Hiseq technology and its gene map and genomic structure were analyzed. Then comparative and phylogenetic analysis of the complete chloroplast genomes of D. moniliforme and its related species were conducted. The chloroplast genome of D. moniliforme was 150 754 bp in length and had a typical quadripartite structure with a large single copy (LSC, 84 818 bp), a small single copy (SSC, 14 124 bp) and two inverted repeats (IRs, 25 906 bp each). A total of 123 chloroplast genes were annotated, including 77 protein-coding genes, 38 tRNA genes and 8 rRNA genes, of which 17 genes contained introns. Bioinformatics analysis identified 53 SSR sites, most of which had A-T base preference. A phylogenetic tree was constructed using the chloroplast genome sequences of 33 Dendrobium species. The results showed that Dendrobium complex species were clustered in a single large branch, indicating that they were closely related. This study provides a scientific basis for the identification of D. moniliforme and the phylogenetic relationship of D. moniliforme complex species necessary for Herbgenomics research.
Nervous system drugs play an important role in the drug research and development, and the cognition related drug become the urgent needs of social development. However, drugs which can regulate cognitive function are seriously inadequate in clinical supply, and faced frustration in research and development process. In this paper, a brief overview of the two types of cognition related drugs (drugs affecting normal cognitive function and improving cognitive dysfunction) were discussed based on the current research status of cognitive pharmacology. The current research and development of new cognition related drugs focuses on regulating neurotransmitters, targeting Aβ and Tau proteins, neuroprotection and vascularization, and still requires new research methods and ideas. In this article, we summed up the research strategies based on the clinical and development of cognition related drugs, especially for the Alzheimer's disease, then we put forward the task and challenge of cognitive pharmacology development. We aimed at providing new ideas for researchers to promote the development of cognitive drugs.
Phytoestrogens exhibit various pharmacological estrogen-like effects, such as in the prevention and treatment of osteoporosis, cardiovascular diseases, tumors, etc., but the specific mechanism is still unclear. In recent years, estrogen receptor alpha-mediated rapid non-genomic effects have been identified to play an important role in the pathogenesis of estrogen-related diseases. The research of phytoestrogens exerting pharmacological effects through non-genomic effects has also received increasing attention. This article summarizes the research progress in estrogen receptor alpha-mediated non-genomic effects and analyzes the possible involvement of rapid non-genomic effects in certain pharmacological effects of phytoestrogens. The future prospects of estrogen receptor-mediated non-genomic effects by phytoestrogens are also discussed.
To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrapTM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L-1 FITC-TCF4 and 100 nmol·L-1 β-catenin. Under these optimized conditions, a high Zxfactor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.
To study the osteoprotective effect of 1, 2, 3, 4, 6-pentyl-O-galloyl-beta-D-glucose (PGG) its anti-osteoblast apoptosis related mechanism was investigated. A model of zebrafish osteoporosis induced by prednisolone (Pred, 25 μmol·L-1) was established in vivo, and calcein staining was used to detect the effect of PGG on the bone area of zebrafish. Bone marrow mesenchymal stem cells were cultured in vitro, and the number of calcified nodules was observed by alizarin red staining, and the relevant indexes of osteoblast differentiation runt-related transcription factor 2 (Runx 2), osteocalcin (OCN) mRNA level were detected by qRT-PCR. The osteoblast cell line MC3T3-E1 cells was cultured in vitro, and 400 μmol·L-1 hydrogen peroxide (H2O2) was used to intervene the injury to detect the effect of PGG on osteoblasts under oxidative stress. The effect of PGG on osteoblast activity was detected by MTT assay. The effect of PGG on apoptosis was observed by Hoechst 33342 staining. Western blot was used to detect the expression of Bcl-2, Bax, nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). DCFH-DA fluorescence staining for detection of reactive oxygen species (ROS) levels. JC-1 staining was used to detect mitochondrial membrane potential levels. The results showed that PGG could significantly increase the vertebral area of the zebrafish model when compared with the model group. On the 14 th day of osteoblast differentiation, the number of calcified nodules in the PGG group was significantly increased when compared with the control group and the mRNA levels of Runx 2 and OCN were also significantly increased. In addition, under oxidative stress, PGG could increase osteoblast viability, significantly reduce the number of apoptotic cells, and increase the ratio of Bcl-2/Bax. Fluorescence staining results show that PGG decreased intracellular ROS fluorescence density and increased mitochondrial membrane potential. Western blot data showed that PGG could promote the expression of Nrf2 in the nuclear and enhance the expression of downstream protein HO-1. In conclusion, PGG could improve osteoporosis in zebrafish, and this effect may be related to the regulation of Nrf2/HO-1 signaling pathway to improve mitochondrial dysfunction, anti-oxidative stress in osteoblast apoptosis and promote bone formation. This study provides new ideas and clues for the discovery of anti-osteoporosis drugs.
Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.
It is difficult to directly observe the structural transformation inside of soft capsules if their shells are opaque. This study was designed to noninvasively in situ measure the structural characteristics of the soft capsules and internal particle distributions to reveal the intrinsic quality of the soft capsules and develop a new technique for reverse engineering and the physical stability evaluation of the soft capsules. In this research, the CT projection images of soft capsules, namely, propolis soft capsules, were collected via synchrotron radiation X-ray micro computed tomography (SR-μCT). After three-dimensional reconstruction, the structural differences of the soft capsules under long-term test and accelerated test for 6 months were quantitatively analyzed by calculating the three-dimensional structure parameters such as volume, number and distribution of the particles inside and the thickness for the wall of the capsules. There were only a small number of particles evenly distributed in the soft capsules stored under common storage condition without layering. On the other hand, the shell wall of the soft capsule turned thinner locally at the occlusal portion and the particles with strong X-ray absorption were densely distributed at the edge of the capsule wall after the accelerated test. This study revealed that the structural parameters of soft capsules obtained by SR-μCT could be used to evaluate the influence of storage environment on the physical stability of soft capsules. The technology provides a new method for quality control and evaluation for the soft capsules.
Hypoxia-activated prodrugs that specifically target tumor tissues were designed by attaching the nitro-aromatic ring carrier molecules that can be degraded in the hypoxic microenvironment of the tumor to the hydroxyamidine group of IDO1 inhibitor compound B and epacadostat. Eleven prodrug compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. Compounds F-1 and F-6, which had a higher stability and drug release rate, were identified by an in vitro stability assay, nitroreductase reduction assay, MTT assay, and an in vivo tumor tissue hypoxia degradation assay, and then evaluated for anti-tumor efficacy in vivo. The results showed that prodrug F-1 inhibited tumor growth by 67.41%, which was significantly higher than 42.31% for the starting drug group. It appeared that the inhibition of IDO1 in the tumor tissue was different from the overall inhibition of IDO1 in vivo. Animal treatment procedures were carried out with the approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.
Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.
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