Aa a characteristic medicinal plant in China, Gentiana rigescens Franch. has the function of protecting the liver and invigorating the spleen. At present, there are a few studies on the content determination method of characteristic components of G. rigescens, so it is necessary to establish a scientific and effective quality control method; In this study, The high performance liquid chromatography (HPLC) fingerprint of G. rigescens was established, based on literature reviewed and characteristic spectrum identified, the source range of G. rigescens quality marker (Q-marker) was screened. The effectiveness of the ingredients and the corresponding targets and pathways was analyzed through network pharmacology, and drew the diagram of ''component-target-pathway''. Qualitative and quantitative analysis of G. rigescens was performed by HPLC, and screen the main marker components leading to the differences between groups which were determined the Q-marker of G. rigescens; The literature and HPLC had determined that five iridoids were the main source of G. rigescens Q-marker. The network pharmacology (effectiveness) and qualitative and quantitative (detectability) analysis of G. rigescens from different producing areas confirmed that gentiopicroside, swertiamarin, and sweroside can be used as the main landmark components, and there were significant differences in their contents among different producing areas; The analysis of G. rigescens from different producing areas was carried out by network pharmacology and chemical fingerprints, it is confirmed can be used as potential Q-marker to provide sufficient theoretical basis for the quality control of G. rigescens in the later period.

Molecular mass distribution of Astragalus polysaccharides is wide. Astragalus polysaccharides prepared by conventional water extraction and alcohol precipitation are mostly mixture of macromolecules. Although studies have shown that Astragalus polysaccharides have two-sided immunomodulation, the relationship between anti-inflammatory components and molecular mass distribution of Astragalus polysaccharides is not clear. Therefore, Astragalus polysaccharides were extracted by water extraction and alcohol precipitation. The relative molecular weight of them was determined by high performance gel permeation chromatography (HPGPC). Astragalus polysaccharides with different molecular weights were separated and prepared by membrane separation. RAW 264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammatory cell model in vitro and the anti-inflammatory polysaccharide were screened. The anti-inflammatory regulation mechanism of Astragalus polysaccharides was analyzed by the LC-MS/MS metabonomics technology. The results showed that APS was composed of APS-Ⅰ (> 2 000 kDa) and APS-Ⅱ (10 kDa). APS-Ⅰ was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-Ⅰ were 0.54∶0.26∶12.24∶17.24∶8.46∶1. APS-Ⅱ was composed of rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-Ⅱ were 0.26∶0.14∶24.04∶0.62∶1. APS-Ⅰ and APS-Ⅱ had no cell toxicity to RAW 264.7 macrophage in the range of 0-100 μg·mL^-1. Compared with the model group, APS-Ⅰ at a concentration of 0-100 μg·mL^-1could significantly inhibit the secretion of NO and TNF-α by RAW 264.7, and can significantly promote the secretion of IL-10. APS-Ⅰ had better anti-inflammatory activity than APS-Ⅱ in vitro. The metabolomics results showed that 32 different metabolites were found between the model group and blank group; APS-Ⅰ group can significantly callback 18 different metabolites; mainly related to arginine biosynthesis, arginine and proline metabolism, pyrimidine metabolism, citric acid cycle (TCA cycle), cysteine and methionine acid metabolism, tryptophan metabolism. This study found that APS-Ⅰ had better anti-inflammatory activity than APS-Ⅱ in vitro, and its mechanism may be closely related to amino acid metabolism and energy metabolism, which indicated the direction for further clarifying the pharmacodynamic material basis of Astragalus polysaccharides.

To establish a quantitative analysis of multi-components by single marker (QAMS) for the determination of Aster souliei Franch., the relative correction factors (f_x) of neochlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, quercetin, apigenin and kaempferol were established by ultra-high performance liquid chromatography with chlorogenic acid as internal reference. Meanwhile, the content of each component was determined by the external standard method (ESM) and QAMS, and a linear regression model was established to verify the feasibility and accuracy of the QAMS. Hierarchical clustering analysis (HCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were used to evaluate the quality of 23 batches of A. souliei. The results showed that the repeatability of each f_x was good. The average content of neochlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, quercetin, apigenin and kaempferol in 23 batches of A. souliei by QAMS was 0.165, 0.234, 6.115, 0.478, 0.484, 3.359, 1.382, 0.210, 0.172, and 0.057 mg·g^-1, respectively. The mean content determined by the ESM method was 0.163, 0.235, 6.172, 0.479, 0.483, 3.343, 1.413, 0.207, 0.171, and 0.056 mg·g^-1. The results of HCA and OPLS-DA analysis show that 23 batches of A. souliei can be divided into two groups based on caffeic acid content. The content of the first group was between 0.873 to 5.647 mg·g^-1, while the second was between 8.524 to 16.705 mg·g^-1. This QAMS method can be used to simply and quickly evaluate the quality A. souliei.

A large number of cancer-associated fibroblasts (CAFs) in tumor tissues create a favorable environment for the development of tumor. CAFs inhibit immune cells activation and viability by cytokine secretion, and CAFs prohibit drugs and immune cells infiltration by producing extracellular matrix to weaken cancer treatment efficacy. Regulating CAFs or overcoming CAFs barriers are new strategies for cancer therapy. Hence, designing nano-carriers for regulating CAFs to suppress tumor progression or promoting drug delivery to tumor site by overcoming CAFs barriers has attracted much attention. Therefore, this manuscript reviewed the recent progresses of nano-carriers for CAFs-targeting cancer therapies, in order to provide a reference for clinical cancer treatment.

Brain-targeted delivery plays an important role in the diagnosis and treatment of neurological diseases, but the existence of blood brain barrier (BBB) limits the development of brain-targeted delivery. As cell-derived nanovesicles, exosomes can participate in the transportation of substances between cells to mediate the communication between cells to play a biological regulatory role in vivo. Due to the low immunogenicity, low toxicity, high engineering and natural crossing over BBB, exosomes play an important role in brain-targeted delivery. In this paper, the composition of exosomes, the mechanism of brain targeted delivery and its role in various brain diseases are systematically described.

Proteasome controls the degradation of proteins closely related to life activities and plays a key role in the maintenance of protein homeostasis. Proteasome activities decrease with aging, followed by the overwhelming production of damaged proteins which far exceed the protein consumption. Accumulation of these proteins leads to various diseases including neurodegenerative diseases. Therefore, inducing toxic protein degradation is considered as a promising solution for the treatment of these diseases, while increasing the activity of proteasome is considered as an important strategy. However, the research in this field is still in the preliminary stage, and this review will focus on the discussion of the research progress of various small molecule proteasome activators, including research methods, pharmacological effects, structure-activity relationships and the existing problems.

Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.

Two new alkaloids along with eleven known ones, were isolated from the 70% ethanol extract of the roots of Scrophularia ningpoensis Hemsl. by various chromatographic methods, including silica gel, Sephadex LH-20, reverse phase C₁₈ and semi-preparative HPLC. Their structures were determined by physicochemical properties and spectroscopic methods, including UV, IR, MS, 1D/2D NMR and ECD. They were identified as 11α-isopropylcytisine (1), 13α-isopropylcytisine (2), uracil (3), (S)-5-hydroxypyrrolidin-2-one (4), pterolactam (5), methyl-L-pyroglutamate (6), kaempferide (7), luteolin (8), 5, 6, 7, 4′-tetramethoxyflavone (9), 6′-hydroxy-2′, 3′, 4, 4′-tetramethoxychalcone (10), scopolin (11), hymexelsin (12), and 8-hydroxycoumarin (13). Among them, compounds 1 and 2 are two new compounds, while compounds 3, 4, 7-12 were isolated from this plant for the first time. An antitumor activity assay showed that compounds 8 and 9 had weak cytotoxicity against breast cancer cells (4T1).

This study identified the exact molecular mechanisms of baicalein on neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 cells. Bioinformatics methods and molecular docking were integrated for predicting the potential targets and mechanisms of baicalein. Immunofluorescence staining and Western blot were used to analyze the predicted key targets [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)], the expression level of protein related to signal transducer and activator of transcription 1/nuclear factor kappa-B (STAT1/NF- κB) signaling pathway and its upstream regulator NADPH oxidase-2 (NOX2), and then the mechanism of baicalein in alleviating neuroinflammation was explored. The results showed that iNOS and COX-2 were predicted as the key targets and NF-κB signaling pathway was one of the important pathways by bioinformatics methods and molecular docking. Experimental verification showed that baicalein could significantly reduce the expression of iNOS and COX-2, inhibit the phosphorylation of NF-κB and STAT1 and the production of NOX2 in LPS-induced BV-2 cells. To sum up, baicalein could effectively inhibit the inflammatory reaction in LPS-induced BV-2 cells through regulating NOX2 (gp91^phox/p47^phox)/STAT1/NF-κB pathway.

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.