This study used metabolomics to explore the improvement effect of raw and honey-processed Glycyrrhizae Radix et Rhizoma on acute kidney injury (AKI) in rats. All animal experiments were approved by the Animal Ethics Committee of Shandong Academy of Chinese Medicine (approval No.: SDZYY20200101001). SD rats were randomly divided into normal group, model group, raw Glycyrrhizae Radix et Rhizoma group (0.9 g·kg^-1) and honey-processed Glycyrrhizae Radix et Rhizoma group (0.9 g·kg^-1), 6 rats in each group. The rats model of acute kidney injury was established by single intraperitoneal injection of cisplatin (CP) and treated with raw and honey-processed Glycyrrhizae Radix et Rhizoma. The pathological changes of renal tissue were evaluated by hematoxylin and eosin (HE) and PAS staining, the contents creatinine (Cr), blood urea nitrogen (BUN) and superoxide dismutase (SOD) in serum were detected. UPLC-Q-TOF/MS was used to study tissue metabolomics to screen the biomarkers affected by raw and honey-processed Glycyrrhizae Radix et Rhizoma and analyz the metabolic pathways. The results showed that compared with the model group, raw and honey-processed Glycyrrhizae Radix et Rhizoma can significantly improve the pathological changes of renal tissue and decrease the content of Cr, BUN and increase the activity of SOD. In addition, honey-processed Glycyrrhizae Radix et Rhizoma can also significantly reduce the kidney index. In tissue samples, 45 biomarkers were measured in AKI rats. Raw Glycyrrhizae Radix et Rhizoma and honey-processed Glycyrrhizae Radix et Rhizoma could simultaneously call back 11 differential metabolites, which were involved in the regulation of glycerophospholipid metabolism, tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glutathione metabolism. In addition, raw Glycyrrhizae Radix et Rhizoma is also involved in the regulation of glycine, serine and threonine metabolism and pyrimidine metabolism. In summary, raw and honey-processed Glycyrrhizae Radix et Rhizoma can participate in the regulation of different metabolic pathways, and play an improvement role in AKI rats by regulating amino acid, lipid metabolism, energy metabolism and oxidative stress.

Bupleuri Radix is commonly used in the traditional Chinese medicine, and saikosaponins are the important active ingredients. In this study, we first established a relative quantitative method for 25 saikosaponins using ultra high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QTrap-MS) in the scheduled multiple reaction monitoring (sMRM) mode. The established method showed good intra-day and intra-day precision, linearity, repeatability and stability. Then the method was applied to compare 37 batches of Bupleuri Radix from different planting areas. The results showed that there was no significant difference in the saikosaponins composition of Bupleuri Radix from different planting areas in Shanxi Province, which indicating that Bupleuri Radix is well adapted to the environment, so it is suitable for widely planting. However, Bupleuri Radix harvested at spring and autumn were differed from those harvested at summer, which indicated that the traditional harvesting experience was reasonable. Correlation analysis showed that saikosaponins a and d were positively correlated with some saponins, and 4 saponins (such as clinoposaponin Ⅻ) showed bigger content variation were identified by coefficient of variation analysis. The LC-MS based pseudotargeted metabonomic method established in this study can be applied to the comprehensive detection of saikosaponins, which providing new method for the quality evaluation of Bupleuri Radix.

Atractylodes chinensis has important medicinal and economic values. In this study, the chloroplast genome sequences of four A. chinensis samples from different producing areas were sequenced using the Illumina platform. The specific DNA barcodes were screened and the germplasm resources of A. chinensis samples from different producing areas and the genetic diversity of the population were analyzed basing on the specific barcodes. The whole chloroplast genomes of the four A. chinensis samples had a typical cyclic tetrad structure, with 112 genes annotated. The comparative genomics results indicated that ccsA and trnC-GCA_petN were potential specific DNA barcodes for intraspecific identification of A. chinensis. Polymerase chain reaction (PCR) analysis of ccsA and trnC-GCA_petN was performed on 256 samples from 14 areas in 9 provinces, and the amplification efficiency was 100%. Sequence analysis showed that ccsA and trnC-GCA_petN had 11 and 22 variant positions, which could identify 16 and 22 haplotypes, respectively. The combined sequence analysis identified 39 haplotypes, named Hap1-Hap39, of which the most abundant and widely distributed genotype was Hap9. Haplotype diversity (H_d) = 0.896 and nucleotide diversity (Pi) = 0.002 22 indicated high genetic diversity at the species level in A. chinensis. The genetic distances of the haplotypes were 0.000 00-0.004 88, indicating that there were small genetic differences among the haplotypes. The results of phylogenetic tree analysis showed that 39 haplotypes had very close genetic relationship, and formed two obvious branches with other groups of the same genus except Atractylodes macrocephala. This study plays an important role in the identification of the origin of A. chinensis and the protection and breeding of germplasm resources.

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. Firstly, the effects of artesunate on cell activity, proliferation and apoptosis of U87 and U251 human glioma cells were explored. It was found that artesunate exerted stronger inhibitory effects on the activity and proliferation of U87 cells than U251 cells. It could significantly promote apoptosis in U87 cells (P < 0.05), while only high dose of artesunate can promote that of U251 cells (P < 0.01), detected by Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained through transcriptome sequencing and differential data analysis by using the lysates of U87 and U251 cells before and after artesunate treatment, aiming to explore the molecular mechanism of distinct artesunate sensitivity to two types of cells. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which apoptosis-related activating transcription factor 4 (ATF4)-DNA damage induced transcript 3 (DDIT3)- polyadenosine diphosphate ribose polymerase 1 (PARP1) signaling axis was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that ATF4-DDIT3-PARP1 signaling axis is the target pathway of artesunate intervening with U87 glioma cells, and PARP1 may be an important gene for U251 cells to develop resistance to artesunate. Our results not only provide fundamental experimental evidence for artesunate as a potential therapeutic drug in glioma treatment, but shed light into overcoming drug resistance in its clinical therapy.

At present, most clinical thrombolytic drugs are plasminogen activators, which are highly dependent on the plasminogen level of the patient. Therefore, the efficacy of those drugs is restricted. Unlike the conventional thrombolytic plasminogen activator drugs, fibrinolytic drugs have direct fibrinolytic activity. Thus, fibrinolytic drugs can directly dissolve the thrombus, and its thromlysis efficacy is not restricted by the patients' plasminogen. This is a new type of thrombolytic drug with higher thrombolytic efficiency and safety, and has become one of the research hotspots at present. Although more and more agents that can be used as fibrinolytic drugs have been discovered, only a few of them can successfully be applied in clinical practice. The mainly underlying reason is the risk of bleeding. In this paper, based on the latest research progress of fibrinolytic drugs, the bleeding mechanisms and coping strategies of fibrinolytic drugs were systematically reviewed, five types of bleeding mechanisms of fibrinolytic drugs were summarized, and three types of coping strategies were proposed. We hope our work can provide theoretical basis for the development of safer and more efficient fibrinolytic drugs.

The air at high altitude is thin and belongs to the environment of low temperature, low oxygen and low pressure. The human brain is the most sensitive to hypoxia. Hypoxia will cause dysfunction of the central nervous system, resulting in high-altitude hypoxic brain injury, including mild high altitude headache and more destructive high altitude cerebral edema (HACE). Recently, with more and more people work and live in high altitude areas, the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance. Non clinical pharmacodynamic evaluation is the basic of drug development, which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research. This review summarizes the cell models and animal models, and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury. We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy, and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.

We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg^-1), medium (8 g·kg^-1) and high (16 g·kg^-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.

ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan. ProTides are aryloxyphosphoramidates (or aryloxyphosphonamidates) which contain a phosphorus atom combined with an amino acid ester and an aryloxy group. These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation, which afford effective solutions to the drawbacks of current nucleoside analogues. At present, ProTide technology has been extensively applied in the field of antiviral research. It has been successful in providing a number of approved drugs and clinical candidates, such as sofosbuvir and so much more, highlighting the promising future in drug discovery. This review summarizes the brief history and characteristics of ProTide technology, as well as its application in the exploration of antiviral drugs.

Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.