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.

Anti-tumor intervention using a combination of drugs shows unique advantages in research and clinical practice. Active ingredients of Chinese herbal medicines can offer many advantages, such as high efficiency, low toxicity, wide effect and multiple targets. At present, the combination active ingredients of Chinese herbal and chemotherapy drugs have attracted increased attention. Nano-drug delivery system provides a good carrier platform for anti-tumor drugs. Nano-carrier-mediated drug combination is a promising strategy. In this paper, we review the mechanisms of the anti-tumor effects of active ingredients of traditional Chinese medicine combined with chemotherapeutic drugs and consider the advantages of drug-loaded nanoparticles, the types and characteristics of carriers. The aim is to provide a reference for the research of effective regimen for anti-tumor therapy.

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.

To investigate the potential hypoglycemic effect of nanosuspensions of honokiol and explore the underlying mechanisms, a high fat diet (HFD) was studied in C57BL/6J mice divided into five groups:normal diet (ND), HFD, HFD/honokiol-sodium carboxymethyl cellulose (CMC-Na) (Hono-CMC, 100 mg·kg^-1), HFD/honokiol-Nano (Hono-Nano, 80 mg·kg^-1), HFD/metformin (HFD/Met, 200 mg·kg^-1). Fasting blood glucose (FBG) and body weights (BW) of mice were measured every seven days. After 30-day treatment, an oral glucose tolerance test (OGTT) was performed, and blood and tissue samples were collected for analysis. All animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. The data showed Hono-Nano and metformin reduced FBG, BW, and markedly improved OGTT of mice compared to HFD group (P < 0.05). Hono-CMC produced nonsignificant impact on FBG, BW of mice, while OGTT of mice was improved by Hono-CMC (P < 0.05). Meanwhile, none of these treated groups showed significant effects on regulating serum insulin levels, but all of them exhibited decreased serum glucagon levels notably compared to the HFD group (P < 0.05). Western blot analysis revealed that honokiol up-regulated levels of p-AMPK and p-FOXO1 in liver tissue of HFD mice (P < 0.05), which resulted in activation of AMPK and inhibition of FOXO1. Moreover, the expression of PEPCK (a key enzyme of gluconeogenesis) was decreased by honokiol (P < 0.05). Taken together, our findings demonstrate that nanosuspension of honokiol is more effective than CMC-Na-suspension of honokiol on blood glucose controlling in HFD mice. The hypoglycemic effects of honokiol might rely on suppressing hepatic gluconeogenesis via activating AMPK and inhibiting FOXO1.

To assess the therapeutic effect of Tao Hong Si Wu decoction (THSWD) on glucocorticoid-induced osteoporosis and its mechanism, the standard products of nine active components in THSWD were accurately weighed and the reserve liquid of standard product was prepared. Then a series of concentration standard liquid was obtained by dilution, and the standard curve was established. The formula of THSWD was proportionally extracted and the nine active components were determined by high performance liquid chromatography (HPLC). Naturally mated to obtain zebrafish embryos after incubation, the zebrafish larvae were cultured in blank E₃ medium until the 3 days post fertilization (DPF), then divided into control group (blank E₃ medium), prednisolone (PNSL) group (25 μmol·L^-1 PNSL), disodium ethydronate (DE) group (15 μmol·L^-1 DE and 25 μmol·L^-1 PNSL), THSWD group (0.1, 1.0 or 10.0 μg·mL^-1 THSWD and 25 μmol·L^-1 PNSL), 15 in each group. The culture was continued until the 10 DPF. The zebrafish was anesthetized and sacrificed, stained with alizarin red S, then the bone staining was observed under a microscope. Quantitative analysis of bone mineralization area and cumulative optical density. Expression of alkaline phosphatase (AKP), type Ⅰ collagen (type Ⅰ), runt-related transcription factor 2 (RUNX-2), osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP) and osteocalcin (OCN) were assessed by quantitative real-time PCR. The mineral contents in zebrafish were measured using inductively coupled plasma-mass spectrometry. In the THSWD water extract, the content of 9 compounds in descending order was as follows:gallic acid > hydroxysafflor yellow A > chlorogenic acid > senkyunolide H > ferulic acid > caffeic acid, senkyunolide Ⅰ > coumaric acid > benzoic acid. Compared with the control group, treatment of zebrafish with 25 μmol·L^-1 prednisolone significantly reduced the area of mineralized bone and cumulative optical density, and the expression of AKP, type Ⅰ, RUNX-2, OPG, OCN gene was also significantly reduced. The levels of Ca, P, K, Mg, Zn and Fe in zebrafish were reduced by 2.8, 2.4, 13.8, 6.6, 8.0 and 8.8 times, respectively. Compared with the prednisolone group, after treating with THSWD, the area of mineralized bones and cumulative optical density value of zebrafish increased significantly and was dose-dependent, and the expression of related genes also increased. The Ca, P, K, Mg, Zn, Fe levels were significantly higher than the prednisolone group. Result show that THSWD has the potential to reverse the effect of glucocorticoid osteoporosis, the mechanism of which is to enhance the activity of osteoblast, promote the expression of bone gelatin and bone mineralization, and increase bone mass.

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 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.

Q-marker is a new concept of quality control for traditional Chinese medicine. Since its introduction in 2016, it has received extensive support and participation from researchers and manufactures of the entire industry. In order to establishing the research level of quality markers, normative research model, we review the proposed core theory and research methods of Chinese medicine quality markers. The definition and scientific connotation of Chinese medicine quality markers are analyzed. The core theories and research methods of quality markers are summarized from five aspects:"effectiveness", "specificity", "transfer and traceability", "compatibility environment" and "measurability" of quality markers. This paper aims to provide useful theoretical and methodological guidance for studying Chinese medicine quality markers.

The blood-brain barrier (BBB) not only maintains the stability of the environment within the central nervous system by controlling the transport of substances on both sides of the blood and brain, but also plays an important role in the R&D of new drugs for neurological disorders. The establishment of an in vitro high-fidelity model to study BBB function is imperative for assessing barrier permeability of drugs and xenobiotics. However, the complexity of the BBB structure makes it difficult to replicate with an in vitro model. Compared to the traditional in vitro BBB model, the BBB-on-chip provides certain advantages in miniaturizing the system, reducing the amount of cells and medium required, and allowing simultaneously induction of shear stress. We review here the BBB-on-chip models from their establishment and characterization to applications in research of neuroinflammation, brain tumor and drug evaluation.

Near-infrared spectroscopy (NIRS) combined with chemometrics can achieve rapid detection in process analysis. After variable selection, the redundant information is effectively removed and the characteristic variables related to the response values are selected. Compared with global model, the complexity is significantly reduced and the prediction accuracy is also improved. In this study, near-infrared spectroscopy analysis combined with different variable selection methods was applied to achieve the rapid detection of baicalin in the extraction process of Scutellaria baicalensis. Data sets were divided based on sample set portioning based on joint x-y distance (SPXY) method. Competitive adaptive weighted resampling method (CARS), random frog (RF) and successive projections algorithm (SPA) were applied to variable selection. Partial least squares (PLS) models were constructed based on above three methods, and the prediction results were compared. After CARS, RF and SPA method, 92, 10 and 17 variables were screened out respectively. According to the performance of the models, CARS method is found to be more effective and suitable than RF and SPA. Furthermore, the characteristic variables selected by CARS method have a better correspondence with the chemical structure of baicalin. The root mean square error (RMSEC) of the calibration set and the root mean square error (RMSEP) of the prediction set are 0.528 2 and 0.720 2 respectively. Compared with the global PLS model, the correlation coefficient of the calibration set (Rc) is increased to 0.979 9 from 0.917 0, and the relative standard errors of prediction (RSEP) is reduced to 5.59% from 10.58%.