Ten novel oleanolic acid (OA) derivatives containing urea or thiourea group were designed and synthesized, the chemical structures were confirmed by ¹H NMR, ¹³C NMR and HR-MS. All of these compounds were evaluated for the inhibitory activity against growth of HepG2 and SGC7901 cells. The results showed that compounds I₃ and Ⅱ₃ exhibited significant antitumor activities with IC₅₀ of 9.4 and 5.5 μmol·L^-1, respectively. Molecular docking studies showed that all these compounds exhibit inhibitory ability against mTOR kinase. Compounds I₃ and Ⅱ₃ were further evaluated for the inhibitory activity against mTOR kinase. The results showed that I₃ and Ⅱ₃ exhibited strong inhibitory effect on mTOR kinase with IC₅₀ values of 0.83 and 0.26 μmol·L^-1.

Nifedipine, a calcium channel antagonist, is metabolized mainly by CYP3A4 to dehydronifedipine. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine nifedipine and dehydronifedipine in human plasma using d₆-nifedipine/d₆-dehydronifedipine as internal standards. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a Hypersil Gold C₁₈ (50 mm×2.1 mm, 1.9 μm). The mobile phase consisted of methanol and 5 mmol·L^-1ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 347.3→254.1 for nifedipine, m/z 345.2→283.9 for dehydronifedipine, m/z 353.3→257.1 for d₆-nifedipine, m/z 351.2→286.9 for d₆-dehydronifedipine. The method had a linear calibration curves over the concentrations of 0.10-80.0 ng·mL^-1 for nifedipine and 0.050-40.0 ng·mL^-1 for dehydronifedipine. The validated LC-MS/MS method has been successfully used study pharmacokinetic interactions of apatinib (CYP3A4 inhibitor) and nifedipine (CYP3A4 substrate) in human. This clinical trial was approved by the society of ethics and conducted in the first hospital of China medical university.

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.

We were interested in ascertaining differences in developmental neurotoxicity in normal and blood-stasis pregnant mice administered orally Rhizoma Curcumae and the underlying molecular biology mechanisms of any differences. To answer these questions, a blood stasis model was induced by being immersion in ice water. C57BL/6 mice with blood stasis, normal C57BL/6 mice, Nrf2 knock out (KO) mice with blood stasis were randomized into control groups and Rhizoma Curcumae exposure groups. The pregnant mice were administered Rhizoma Curcumae during pregnant day 5 to day 18. The neurodevelopment reflex was examined by the positive occurring time of avoidance precipice reflex tests. Measurement of glutathione (GSH) in brain of the offspring was performed by colorimetric assays. Transcription factor NF-E2-related factor 2 (Nrf2), glutamate cysteine ligase catalytic subunit (GCLc), and glutamate cysteine ligase modifier subunit (GCLm) mRNA and protein expression in brain of the offspring were examined by real-time RT-PCR and Western blot, respectively. All animal care and experiments procedures were reviewed and approved by the Animal Care and Use Committee of Qiqihar Medical College. Our results demonstrated for the first time evidence that C57BL/6 mice treated with Rhizoma Curcumae (10.0 g·kg^-1) extended the positive occurring time of avoidance precipice reflex tests of offspring mice compared with the normal control group (P < 0.05). We could not find any significant change in that of blood-stasis pregnant mice offspring compared with the normal control group (P>0.05). Compared with the normal control group, level of glutathione, mRNA and protein expression of Nrf2, GCLc, and GCLm significantly increased in brain of the offspring of blood-stasis pregnant mice (all P < 0.05). However, mice treated with Rhizoma Curcumae (10.0 g·kg^-1) did not change those of offspring (all P>0.05). Knock out Nrf2 using CRISPR/Cas9 extended the positive occurring time of avoidance precipice reflex tests of offspring of blood-stasis pregnant mice (P < 0.05). To conclude, developmental neurotoxicity of the blood-stasis pregnant mice to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Cold-induced Nrf2 activation has important roles in "YOU-GU-WU-YUN" phenomenon of Rhizoma Curcumae.

Though red yeast rice (RYR) has been used as medicine for centuries, few study has been reported about its biological activities related to traditional medicinal application and marketed RYR showed poor consistency in quality. In this study, with comprehensive investigation of their production processes and field acquisition samples including those from genuine producing area, an ultra performance liquid chromatographic (UPLC) method was firstly established to discriminate RYR for different applications based on their secondary metabolites fingerprint. It was performed on a CAPCELL CORE AQ column (100 mm×4.6 mm, 2.7 μm), with PDA (range:200-650 nm, extracted:237 nm) and ELSD detection. The mobile phase used was water (A) and acetonitrile (B) both containing 0.1% formic acid at gradient elution (0-15 min, 50% B→85% B (linear); 15-16 min, 85% B→50% B (linear) and maintained until 21 min), with a flow rate of 0.5 mL·min^-1. The method established was fully validated in agreement with guidelines of Chinese Pharmacopeia. Common metabolites were found in RYR for same application and the fingerprints of RYR for food coloring or brewing from various manufacturers had similarities above 0.90. Meanwhile, significant differences were observed among the fingerprints for various applications and discrimination could be achieved by principal component analysis (PCA). Lovastatin was absence in RYRs for food coloring or brewing, and the fingerprint of traditional medicinal RYR was similar to that of RYR for brewing. However, standardization was required for RYR containing lovastatin because of their significant differences from various manufacturers in fingerprints and lovastatin content. The results demonstrated the feasibility to discriminate RYR for different applications by the secondary metabolites fingerprint method established in this study, which provides a scientific basis to investigate the relationship between biological activities of medicinal RYR and their corresponding secondary metabolites, and further aid their quality standardization and improvement.

Atherosclerosis refers to vascular pathological changes in which vascular lumen was narrowed or blocked by cholesterol or fat existed in vascular endothelium, which could induce serious cardiovascular events. The pathogenesis of atherosclerosis is complicated extremely. Vascular endothelial dysfunction initiated the plague formation and deterioration, which determined the prognosis of atherosclerosis. Circular RNA (circRNA) is a special endogenous non-coding RNA, which has become a research hotpot in the field of non-coding RNA. This review aims to bring together the recent research on the pathogenesis and pathological process of endothelial dysfunction, and the regulative effect of circRNA on it. Our article will provide new targets and new ideas for the research and development of anti-atherosclerosis drugs.

A mouse model of cholestatic liver fibrosis was established by bile duct ligation (BDL) method. The effect of ginsenoside Rg1 in the disease progress and the mechanism of cholestatic liver fibrosis are investigated in this mouse model. All animal experiments in this paper have been approved by the Unit Ethics Committee. Analysis of serum biochemical indicators and pathological sections assessed liver function, liver damage and fibrosis in mice. Immunohistochemistry and Western blot assays were used to detect vascular cell adhesion molecule-1 (VCAM-1) in BDL-induced mice. Nuclear factor-κB (NF-κB) and inflammatory factors were detected to investigate related mechanism of Rg1. The results showed that expression of VCAM-1 was up-regulated and peaked at 7 days, followed by decreased expression, but still efficiently expressed compared to the sham-operated group. Compared with the model group, 40 mg·kg^-1·d^-1 Rg1 treatment reduced serum aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin (T.Bili) levels (P < 0.05 or P < 0.01) and liver function damage, alleviated BDL-induced liver fibrosis, significantly down-regulated the expression of VCAM-1 (P < 0.05), and inhibited the inflammatory response. In addition, Rg1 significantly reduced NF-κB p65 level in the cellular nucleus (P < 0.05). This study demonstrates that VCAM-1 is dynamically altered during BDL-induced liver fibrosis. Rg1 could dampen inflammation and alleviate cholestatic liver fibrosis via regulation of the NF-κB/VCAM-1 pathway. The results provide an experimental basis for Rg1 application for treating liver fibrosis.

The quality control of traditional Chinese medicine provides the premise of its modernization and globalization. Currently, the dual quality control based on chemical benchmark and effect benchmark has been recognized domestically and internationally. Research efforts have lead to establishment of a series of effective quality control methods based on chemical components, medicinal properties, microscopic characteristics, material constituents and pharmacodynamic targets. In the study of quality control based on chemical benchmarks, fruitful results on fingerprints, DNA barcodes, and quality markers have been achieved. However, due to a variety of factors, such as growth period, origin, growth environment and preparation process of traditional Chinese medicine, the quality control of traditional Chinese medicine based on chemical benchmarks remains difficult to fully reflect the quality of traditional Chinese medicine. At present, there is still a dispute on how to accurately reflect the quality of traditional Chinese medicines based on chemical benchmarks. For example, the index components selected in the Chinese medicine quality standards are difficult to totally reflect all the components of Chinese medicine, and the relevance between the index components versus therapeutic effect is not yet clear. In view of the complex signal network by cascade reaction and crosstalk of multi-signaling pathways within an organism, and the coordinated regulation of multi-components and multi-targets of traditional Chinese medicine, there may be different components regulating the same signal network or situations where the amount of certain chemical components within a range is not sufficient to cause a change in the signal network. Therefore, the quality control of traditional Chinese medicine based on the effect benchmark may be a useful supplement to the quality standard of traditional Chinese medicine. This paper proposes a Q-biomarker research strategy based on the effect benchmark in order to provide a methodological reference for the quality control research of traditional Chinese medicine.

The research is aimed to investigate the effect of genistein (GEN) on the apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 cells and explore the pharmacological mechanism of GEN anti-atherosclerosis (AS). RAW264.7 cells were activated by LPS, the level of TNF-α and IL-6 mRNA were detected by qRT-PCR, the expression of COX-2 and iNOS were detected by Western blot. RAW264.7 cells were pretreated with GEN for 2 h, and then incubated with LPS for 24 h. After that, CCK8 kit was used for the cell viability, Annexin V-FITC/PI kit for the apoptosis of cell. qRT-PCR was used to detect the level of CHOP, caspase-3 and miR-21. Western blot was used to detect the expression of CHOP and caspase-3. Results showed that LPS (1 000 ng·mL^-1) increased the expression of TNF-α, IL-6, COX-2 and iNOS in RAW264.7 cells compared with that in control group. GEN inhibited the cell activity and the level of miR-21, promoted the expression of CHOP and caspase-3 in LPS-activated RAW264.7 cells in a dose-dependent manner. miR-21 up inhibited the expression of CHOP and caspase-3 in LPS-activated RAW264.7 cells and this process was reversed by GEN treatment. miR-21 down promoted the expression of CHOP and caspase-3, which were further enhanced by GEN. These results indicate that GEN promotes the apoptosis of RAW264.7 cells activated by LPS through down regulating miR-21 and activating endoplasmic reticulum (ER) stress pathway.

The chemical composition of traditional Chinese medicine (TCM) compounds is complex, the treatment is broad, and the quality control indexes cannot accurately reflect the functional properties. According to the above problems, the authors take the research process of quality markers of Qizhiweitong granules as an example to innovate the research ideas and technical methods, and constructed five progressive steps of TCM compounds quality control and evaluation model:"based on function, to figure out the attending", "components and pharmacodynamics correlation, multiple components with multiple effects", "to analyze the components, and systematically integrate them", "spectrum and effect correlation, from a spectrum to see the efficiency", and "from the content-effect colour atla to see the quality". Based on the multiple effects of components, multiple components of multi-effect pharmacological efficacy evaluation system were established. All-time isobaric multiwavelength fusion fingerprint technology was improved and developed. "Spectrum-effect colour atla" software was research and developed for the first time, to realize the "visualization" of TCM efficacy. The aim of this work is to provide an exploratory solution for the integrated quality control of TCM compounds.