Network pharmacology and experimental validation of effects of total saponins extracted from Abrus cantoniensis Hance on acetaminophen-induced liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Abrus cantoniensis Hance (AC), an abrus cantoniensis herb, is a Chinese medicinal herb used for the treatment of hepatitis. Total saponins extracted from AC (ACS) are a compound of triterpenoid saponins, which have protective properties against both chemical and immunological liver injuries. Nevertheless, ACS has not been proven to have an influence on drug-induced liver injury (DILI). AIM OF THE STUDY: This study used network pharmacology and experiments to investigate the effects of ACS on acetaminophen (APAP)-induced liver injury. MATERIALS AND METHODS: The targets associated with ACS and DILI were obtained from online databases. Cytoscape software was utilized to construct a "compound-target" network. In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to analyze the related signaling pathways impacted by ACS. AutoDock Vina was utilized to evaluate the binding affinity between bioactive compounds and the key targets. To validate the findings of network pharmacology, in vitro and in vivo experiments were conducted. Cell viability assay, transaminase activity detection, immunofluorescence assay, immunohistochemistry staining, RT-qPCR, and western blotting were utilized to explore the effects of ACS. RESULTS: 25 active compounds and 217 targets of ACS were screened, of which 94 common targets were considered as potential targets for ACS treating APAP-induced liver injury. GO and KEGG analyses showed that the effects of ACS exert their effects on liver injury through suppressing inflammatory response, oxidative stress, and apoptosis. Molecular docking results demonstrated that core active compounds of ACS were successfully docked to core targets such as CASP3, BCL2L1, MAPK8, MAPK14, PTGS2, and NOS2. In vitro experiments showed that ACS effectively attenuated APAP-induced damage through suppressing transaminase activity and attenuating apoptosis. Furthermore, in vivo studies demonstrated that ACS alleviated pathological changes in APAP-treated mice and attenuated inflammatory response. Additionally, ACS downregulated the expression of iNOS, COX2, and Caspase-3, and upregulated the expression of Bcl-2. ACS also suppressed the MAPK signaling pathway. CONCLUSIONS: This study demonstrated that ACS is a hepatoprotective drug through the combination of network pharmacology and in vitro and in vivo experiments. The findings reveal that ACS effectively attenuate APAP-induced oxidative stress, apoptosis, and inflammation through inhibiting the MAPK signaling pathway. Consequently, this research offers novel evidence supporting the potential preventive efficacy of ACS.

Multi-labeled neural network model for automatically processing cardiomyocyte mechanical beating signals in drug assessment.

High-throughput cardiotoxicity assessment is important for large-scale preclinical screening in novel drug development. To improve the efficiency of drug development and avoid drug-induced cardiotoxicity, there is a huge demand to explore the automatic and intelligent drug assessment platforms for preclinical cardiotoxicity investigations. In this work, we proposed an automatic and intelligent strategy that combined automatic feature extraction and multi-labeled neural network (MLNN) to process cardiomyocytes mechanical beating signals detected by an interdigital electrode biosensor for the assessment of drug-induced cardiotoxicity. Taking advantages of artificial neural network, our work not only classified different drugs inducing different cardiotoxicities but also predicted drug concentrations representing severity of cardiotoxicity. This has not been achieved by conventional strategies like principal component analysis and visualized heatmap. MLNN analysis showed high accuracy (up to 96%) and large AUC (more than 98%) for classification of different drug-induced cardiotoxicities. There was a high correlation (over 0.90) between concentrations reported by MLNN and experimentally treated concentrations of various drugs, demonstrating great capacity of our intelligent strategy to predict the severity of drug-induced cardiotoxicity. This new intelligent bio-signal processing algorithm is a promising method for identification and classification of drug-induced cardiotoxicity in cardiological and pharmaceutical applications.

Overview of piperlongumine analogues and their therapeutic potential.

Natural products have long been an important source for discovery of new drugs to treat human diseases. Piperlongumine (PL) is an amide alkaloid isolated from Piper longum L. (long piper) and other piper plants and has received widespread attention because of its diverse biological activities. A large number of PL derivatives have been designed, synthesized and assessed in many pharmacological functions, including antiplatelet aggregation, neuroprotective activities, anti-diabetic activities, anti-inflammatory activities, anti-senolytic activities, immune activities, and antitumor activities. Among them, the anti-tumor effects and application of PL and its derivatives are most extensively studied. We herein summarize the development of PL derivatives, the structure and activity relationships (SARs), and their therapeutic potential on the treatments of various diseases, especially against cancer. We also discussed the challenges and future directions associated with PL and its derivatives in these indications.

Total saponins extracted from Abrus cantoniensis Hance suppress hepatitis B virus replication in vitro and in rAAV8-1.3HBV transfected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatitis B, an infectious disease caused by hepatitis B virus (HBV), is still a serious problem affecting global public health. Abrus cantoniensis Hance (AC), a traditional Chinese medicinal herb, has been used as a folk medicine for treating hepatitis in China from ancient times. However, its active ingredients are still unclear. AIM OF STUDY: Our previous study indicated that saponins extracted from AC (ACS) were the active anti-HBV ingredients in AC. This study aimed to further investigate the anti-HBV effect of ACS in vitro and in vivo. MATERIALS AND METHODS: HepG2.2.15 cells which consecutively produce HBV DNA and HBV antigens were used for in vitro test, and C57BL/6 mice infected by a recombinant adeno-associated virus 8 vector carrying 1.3 copies of HBV genome (rAAV8-HBV1.3) were used for in vivo test. The histopathological changes and the immune indices were evaluated in mice model. Genechip was conducted to identify genes and pathways regulated by ACS in HepG2.2.15 cells. RESULTS: In this study, we confirmed that ACS treatment prominently inhibited production of HBV DNA, Hepatitis Be Antigen (HBeAg), and Hepatitis B surface antigen (HBsAg) in HepG2.2.15 cells. ACS treatment also decreased serum HBsAg, HBeAg, and HBV DNA level in rAAV8-1.3HBV transfected mice, which is in accordance with the in vitro results. Moreover, HBV infection-induced liver inflammation was significantly relieved by ACS, which could be observed in H&E staining and immunohistochemistry of HBcAg. ACS treatment elevated IFN-γ level in mice serum and increased CD4+ T cell percentage in splenocytes. KEGG pathway analysis showed that phenylalanine metabolism pathway and tyrosine metabolism pathway were greatly regulated by ACS treatment. CONCLUSION: ACS exerted potent inhibitory effects on HBV replication both in vivo and in vitro, which may provide basis for its potential clinical usage.

Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism.

Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-hydroxyl phosphinates in excellent yields with up to 99 : 1 dr. The diastereoselectivity was induced by a reversible conversion of less stable stereomer of product to that of a more stable one via an equilibrium, which was confirmed by aldehyde/ketone exchanging reaction. Toward the exchange, aliphatic or aldehyde carbonyl were more active than aromatic or ketone carbonyls, respectively. The stability difference between the two diastereomers was controlled by the sizes of substituents linking to phosphorus or α-carbon.

A novel LC-MS/MS method for determination of tissue distribution and excretion of timosaponin B-II in rat biological matrices.

Timosaponin B-II (TB-II) is a natural bioactive steroid glycoside extracted from the Chinese medicinal herb Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has been demonstrated to have a good anti-inflammatory effect and a low bioavailability (1.1%). Clinical research has focused on developing it into a completely new medicine. In this study, a rapid and sensitive analytical method based on LC-MS/MS has been developed for the determination of TB-II in rat biological matrices (tissues, bile, urine and feces samples). The analytes and internal standard were isolated from 100 µL samples by solid-phase extraction and then separated using a DIKMA Inertsil ODS-3 column (5 µm, 2.1 × 150 mm) with an isocratic mobile phase consisting of acetonitrile-0.05% formic acid (35:65) at a flow rate of 0.25 mL/min. Calibration curves (1/χ(2) -weighted) offered satisfactory linearity (r(2) ≥ 0.990) within the test range. The accuracy, precision, recoveries and matrix effects were satisfactory in all the biological matrices examined. The assay was successfully applied to a tissue distribution and excretion study in rats. The preclinical data are useful for the design of clinical trials of TB-II.

[Qualitative fingerprint and quantitative determination of caffeic acid in compound dandelion enema].

OBJECTIVE: To establish a qualitative and quantitative reversed-phase high-performance liquid chromatography (RP-HPLC) with fingerprinting technique for quality control of compound dandelion enema. METHODS: HPLC was utilized for quality assessment of 10 batches of samples. RP-HPLC analysis was performed on a Hypersil BDS C18 column (4.6 mm x 250 mm, 5 microm) with the mixture of acetonitrile (A) and potassium phosphate solution (B) (pH3.2) as the mobile phase in gradient mode. The concentrations of solvent A were 10%, 80% and 80% at 0, 38 and 40 min, respectively. The column temperature was set at 35 degrees C, the flow rate at 0.7 ml/min and the detection wavelength at 254 nm. RESULTS: HPLC fingerprinting was established from the 10 batches, and the data showed 23 characteristic peaks in the compound dandelion enema for use as index peaks for qualitative identification. Comparison of the retention time and the on-line UV spectra of the samples with the chemical standards identified peaks 3, 4 and 8 as protocatechualdehyde, caffeic acid and ferulic acid, respectively. The contents of caffeic acid in the compound dandelion enema ranged between 63.7 and 136.8 microg/ml. CONCLUSION: High specific chromatographic fingerprinting and quantitative measurement of caffeic acid allows rigorous quality control of compound dandelion enema.

[High-performance liquid chromatography combined with mass spectrum analysis for chromatographic fingerprinting of compound dandelion enema].

OBJECTIVE: To identify the active components of compound dandelion enema, a preparation from 7 traditional Chinese herbal drugs for treatment of gynecological diseases. METHODS: Three-dimensional high-performance liquid chromatography (3D-HPLC) was employed to separate the ethyl acetate extract of compound dandelion Enema, and HPLC combined with mass spectrum (MS) analysis used for chromatographic fingerprinting. RESULT: By comparing the ionic fragments of MS and retention time of each peak, the main active components in compound dandelion enema were determined, including caffeic acid, ferulic acid and protocatechualdehyde. CONCLUSION: HPLC coupled with mass spectroscopy can be used for qualitative analysis of compound dandelion enema.

[High-performance capillary electrophoresis for determining caffeic acid content in Fujie enema and Taraxacum mongolicum Hand.-Mazz].

OBJECTIVE: To determine caffeic acid content in Fujie enema and the crude traditional Chinese herbal drug Taraxacum mongolicum Hand.-Mazz. for controlling the quality of the enema at the levels of both the crude drugs and the final product. METHODS: Caffeic acid content in both the enema and the crude drug was determined at 313 nm Using high-performance capillary electrophoresis (HPCE), under the optimized conditions achieved with a fused-silica capillary tube (75 micromx0 cm) and 20 mmol/L borate running buffer (pH=9.18) at a constant voltage of 12 kV and a sampling time of 5 s at 25 degrees Celsius. RESULTS: The calibration curve displayed good linear relationship within caffeic acid concentration range of 10 to 100 microg/ml (r=0.999 2). The regression equation was Y=1002.45X-327.87, and the average recovery was more than 95%. CONCLUSION: HPCE is simple, rapid and sensitive in separation and determination of caffeic acid in Fujie enema and the crude drug of Taraxacum mongolicum Hand.-Mazz.