Based on coumarin core structure as the procaspase-3 activator 1541 from our previous study, twelve coumarin derivatives bearing benzothiazole or benzene moiety were designed and synthesized. Target compounds were evaluated for in vitro antitumor activity against a procaspase-3 overexpressing cancer cell line (human histiocytic lymphoma cell, U937) and a procaspase-3 no-expression cancer cell line (human breast adenocarcinoma cell, MCF-7) to rule out off-target effects. The results revealed that coumarin derivatives bearing benzothiazole showed more potent inhibition activity and selectivity against procaspase-3 over-expressing cancer cell line (U937) than procaspase-3 low-sensitive cancer cell line (MCF-7). Caspase-3 activity evaluation showed that coumarin derivatives bearing benzothiazole showed remarkable caspase-3 activation activity, among them, compound 5f displayed the strongest activity with 93% degree. Flow cytometric assay revealed that compound 5f could inhibit proliferation of tumor cells by inducing apoptosis. Procaspase-3 activity assay showed that compound 5f showed strong procaspase-3 activation activity.

Pyrrolizidine alkaloids (PAs) are a class of hepatotoxic compounds that are largely found in plants. "Zicao" is one of the most commonly-used Chinese herbal medicines from multiple sources, owing to its anti-inflammatory and wound healing effects. However, many studies have shown that this herb and its relative species contain hepatotoxic PAs. These PAs may cause hepatic sinusoidal obstruction syndrome following metabolic activation, and are therefore considered as potential toxic substances. Even though the toxicity of "Zicao" in clinical use has not been reported, the existence of PAs will undoubtedly post a threat for its safety in long-term use. It has now become the focus of many researchers to disclose and prevent its potential risk of intoxication. This review summarizes recent progress and key scientific evidence found in the research of pyrrolizidine alkaloids from "Zicao" and its relative species, including their metabolic toxicity. We comment on the need of future studies, such as providing a reference or guidance for safety evaluation of this medicinal herb in clinical practice.

Lipid droplets (LDs) are ubiquitous dynamic organelles that store and supply lipids in all eukaryotic and some prokaryotic cells for energy metabolism, membrane synthesis and production of essential lipid-derived molecules. There is increasing evidence that hepatitis C virus (HCV) has co-evolved due to its lack of lipid biosynthetic pathways to utilize host lipid metabolic pathways to establish a suitable environment for virus proliferation and obtain the necessary components, eventually promote the assembly and transportation of virus. In this review, we outline the relationship between HCV life cycle and lipid droplet biosynthesis and metabolism, with the aim to discover potential antiviral targets for development of new therapeutic interventions.

To determine relative molecular weight of astragalus polysaccharides (APs), we used Shodex GS620 gel permeation chromatographic column and differential refraction detector (GPC-RI) with dextran as a reference. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and GPC combined with multi-angle laser light scattering detection (GPC-MALLS) were also used.GPC-RI measure showed four peaks of APs, with the M_w of 1 380 000, 231 000, 18 000, and 480, respectively. Three main peaks were found by GPC-RI-MALLS with the M_w as 1 148 000, 180 000, and 43 000, respectively. Strong signals in 155 000 and 18 000 were detected by MALDI-TOF-MS, which also indicated the sugar moieties of the APs as hexoses. From our study, we found that the GPC-RI method with universal correction is most suitable for M_w determination of the APs. Nevertheless, the three methods should be combined and contrasted with each other to obtain accurate information in research of polysaccharides from Chinese medicine.

In this paper, multifunctional silver-graphene quantum dot nanoparticles coated with phospholipids (ADG-DDPC) were prepared and their properties were evaluated in vitro. Cationic phospholipids 1, 2-diolefinoxy-3-trimethy-laminopropane (DOTAP) was absorbed first onto the surface of the core of silver nanoparticle (AgNPs) through the mutual attraction between the positive and negative charge. Based on the principle of phase transformation and hydrophobic interaction, dstearyl-phosphatidylglycolamine-polyethylene-glycol-cyclic-cRGD peptide (DSPE-PEG₂₀₀₀-cRGD) self-assembled onto the outlayer of DOTAP of AgNPs. A stable multifunctional nano-preparation was formed and its ultraviolet absorption, particle size distribution, morphology, in vitro release behavior, ability to kill cancer cells and cell uptake were studied. The maximum UV absorption of the synthesized nanometer preparation was about 400 nm. Malvern particle size meter and transmission electron microscope showed that the particle size of the nano-preparation was about 30-40 nm and its particle size distribution was uniform. The in vitro release of nano-preparation was positively correlated with the concentration of H₂O₂. The IC₅₀ value of AgNPs for tumor cells was (347.78±0.06) ng·mL^-1, and the IC₅₀ value of ADG-DDPC for tumor cells was (209.68±0.09) ng·mL^-1, indicating that ADG-DDPC possessed a stronger cytotoxicity than that of AgNPs. Cell uptake experiment showed that ADG-DDPC could be absorbed by tumor cells and exhibited fluoresce inside those cells. In conclusion, ADG-DDPC was successfully prepared, and in vitro characterization study pointed to that the nano-preparation exhibits a higher antitumor activity than AgNPs.

The quality definition of traditional Chinese medicine (TCM) is a hot area in modern research of TCM. In recent years, the characteristics of one herb with multiple effects have been widely accepted and studied. The typical opposite-effect of herbs is considered as a special part of one herb with multiple effects, and was summarized in this paper. Sanqi was used as an example of opposite-effect herbs for developing the strategies and approaches on the Q-markers. The traditional opposite-effect should be studied by modern pharmacological research methods. The correlation of the chemical components with the opposite effects should be established in order to verify the material basis and evaluate the mechanism including targets and pathways. The unique characteristics of chemical components should be analyzed and defined. Finally, the Q-markers of the opposite effect herb will be confirmed. This paper provides a useful reference for the precise quality control of herbal opposite-effects.

Hypophosphatemia is a common metabolism disease in humans. Fibroblast growth factor 23 (FGF23) inhibits phosphate reabsorption by targeting on the renal tubules. FGF23^C-tail contains 73 amino acids from C-terminus of FGF23, serves as an inhibitor of FGF23, and can increase phosphate reabsorption. Therefore, FGF23^C-tail is an important drug for hypophosphatemia. In this paper, we constructed a fusion protein of FGF23^C-tail with HSA, and investigated the expression of the fusion protein in the Pichia pastoris system. The recombinant gene was constructed by fusion PCR. A high-yield strain was selected by G418 resistance and fermentation yield, and the expression yield was 43.7 mg·L^-1 in flask. In 5 L fermenters, the highest expression yield could reach 265.6 mg·L^-1. FGF23^C-tail-HSA could be used as an inhibitor for FGF23, and could significantly increase blood phosphorus levels in rats. The procedures for care and use of animals were approved by the Ethics Committee of YiChun University. This paper provided a basis research for further studying physiological activity of FGF23^C-tail-HSA.

Ionic liquids are not limited to the traditional use of solvents because of their high permeability and excellent physicochemical and unique biological properties. Nowadays, with the deep understanding of their toxicity and biocompatibility, ionic liquids have been tailored as novel solutions to address potential problems of marketed drugs. Based on the research and development of modified new drugs, ionic liquids have been incorporated into drug synthesis and emerged as attractive environmental-friendly reaction media with milder reaction conditions, higher yields and easier reaction workups and drug delivery systems. In addition, they have been designed for effective drug carriers removing undesirable properties of solid drugs. Further, ionic liquids forming active pharmaceutical ingredients dedicated to the liquefaction of drugs for promising clinical applications.

This study offers preliminary insight into the phytoestrogen activity and mechanism of rehmapicrogenin. In this study, we characterized the estrogenic activity of rehmapicrogenin using immature female mice in vivo and MCF-7 cell proliferation assay in vitro. All the procedures for the care of the mice were conducted in accordance with the Regulations of Experimental Animal Administration issued by the State Committee of Science and Technology of the People's Republic of China. Uterine wet weight/body mass ratios, Western blot assay for estrogen receptor, and serum estrogen levels of estradiol (E₂), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were investigated. The effects of rehmapicrogenin, and the estrogen receptor antagonist ICI182, 780, the estrogen receptor alpha antagonist MPP, the estrogen receptor beta antagonist THC, the G-protein coupled receptor 30 antagonist G15 combined with rehmapicrogenin on cell proliferation were examined in MCF-7 cells. Rehmapicrogenin (50 mg·kg^-1) treatments demonstrated significant estrogenic activity by promoting the development of uterus in immature female mice, as well as increasing the expression of estrogen receptor alpha (ERα) and G-protein coupled receptor 30 (GPR30) at the protein level in uterus, and decreasing FSH and LH compared with the control group. Meanwhile, rehmapicrogenin (6 and 8 μmol·L^-1) promoted the proliferation of MCF-7 cells, which were significantly antagonized by ICI182, 780, MPP and G15. This study demonstrates rehmapicrogenin exerts estrogenic effects through ERα and GPR30.

This study was designed to compare the antithrombotic effects of salvianolic acid A and aspirin. The anti-platelet aggregation and anticoagulant effects of salvianolic acid A and aspirin in vitro and in vivo were investigated in normal rats. The anti-cerebral ischemia and anti-platelet aggregation effects of salvianolic acid A and aspirin were also investigated in rats with thrombotic cerebral ischemia. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. The results of antiplatelet aggregation in vitro and in vivo showed that salvianolic acid A could mildly inhibit adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (THR)-induced antiplatelet aggregation in a dose-dependent manner, while aspirin played a strong inhibitory effect on AA-induced platelet aggregation in vivo. The effects of salvianolic acid A and aspirin on the coagulation system were similar. At the same time, the results of maximum platelet aggregation rate (MAR) in the rat cerebral ischemia model[MAR_ADP=(41.67±4.55)%, MAR_AA=(53.22±2.83)%, MAR_THR=(73.33±5.04)%] indicated that salvianolic acid A could mildly inhibit ADP and AA-induced antiplatelet aggregation[MAR_ADP=(26.13±4.60)%, MAR_AA=(35.53±13.73)%, P < 0.01], while aspirin played a strong inhibitory effect on AA-induced platelet aggregation[MAR_AA=(8.13±2.99)%]. Salvianolic acid A (10 mg·kg^-1) significantly improved the neurological function, cerebral infarction volume[(10.77±7.80)%] and brain edema[(79.72±0.83)%] compared with the model group[(43.50±12.69)%, (82.25±0.89)%] (P < 0.01), while the effect of aspirin (100 mg·kg^-1) was not obvious. The above results suggest that compared with aspirin, salvianolic acid A provided a mild inhibitory effect on platelet aggregation and protected against cerebral ischemia induced by thrombus. Therefore, salvianolic acid A has a good application prospect in the prevention and treatment of thrombotic diseases.