ß-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation.

Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. ß-Boswellic acid (ß-BA), the main component of the folk medicine Boswellia serrata (B. serrata), has been reported to be effective in various diseases including tumors. In this work, we demonstrated that ß-BA could inhibit breast precancerous lesions in rat disease models. Consistently, ß-BA could suppress proliferation and induce apoptosis on MCF-10AT without significantly influencing MCF-10A. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that ß-BA may interfere with the metabolic pathway. Metabolism-related assays showed that ß-BA suppressed glycolysis and reduced ATP production, which then activated the AMPK pathway and inhibited the mTOR pathway to limit MCF-10AT proliferation. Further molecular docking analysis suggested that GLUT1 might be the target of ß-BA. Forced expression of GLUT1 could rescue the glycolysis suppression and survival limitation induced by ß-BA on MCF-10AT. Taken together, ß-BA could relieve precancerous lesions in vivo and in vitro through GLUT1 targeting-induced glycolysis suppression and AMPK/mTOR pathway alterations. Here, we offered a molecular basis for ß-BA to be developed as a promising drug candidate for the prevention of breast precancerous lesions.

[~1H-NMR-based metabonomics analysis of the acute hepatotoxicity mechanism of Artemisia argyi essential oil].

This study based on~1H-NMR urine metabolomics technique combined with biochemical indicators to focus on studying the acute hepatotoxicity mechanism of Artemisia argyi essential oil( AAEO). In order to further explore the acute hepatotoxicity mechanism of AAEO,the researchers collected the urine nuclear magnetic data of rats in different periods of high and low doses of olive oil and AAEO group. Using the principal component analysis( PCA) and orthogonal partial least squares-discrimination analysis( OPLSDA) to analyze the endogenous small molecule metabolites in rat urine to study the effects of AAEO on the metabolic process of normal rats. The results showed there was a significant difference between the olive oil group and the AAEO group,the PCA scores chart demonstrated that there was no obvious separation tendency in the urine of olive oil group rats 0-6,6-12,12-24 h,and the metabolic components were distributed in aggregation pattern. The urinary metabolic trajectory of the rats in the AAEO group was conspicuously separated at 0-6,6-12,12-24 h. The experiments proved that the analysis of metabolites by~1H-NMR found that AAEO caused metabolic disorders in rats and produced acute hepatotoxicity. After metabolite differential comparison,it was speculated that the mechanism of acute hepatotoxicity may be involved in the tricarboxylic acid cycle and energy metabolism,while the citrate and oleanolic acid would be the potential biomarkers. This study discussed that the acute hepatotoxicity mechanism of AAEO was used to provide the experimental data for the clinical prescription of Artemisia argyi.

Molecular network-based analysis of the mechanism of liver injury induced by volatile oils from Artemisiae argyi folium.

BACKGROUND: Volatile oils from Artemisiae argyi folium (VOAAF) is reported with hepatotoxicity, but the underlying mechanism is still unclear. METHODS: In the present study this molecular mechanism was explored with the Ingenuity Pathway Analysis (IPA). The chemical components of the VOAAF were searched in the database, and their target proteins were all identified in the PubChem, while drug-induced liver injury (DILI) genes were searched in the PubMed gene databases. The molecular network of protein targets for VOAAF and DILI genes was built with the IPA. The canonical pathways between the 2 networks were compared to decipher the molecular mechanisms of the liver injury induced by VOAAF. RESULTS: There were 159 target proteins for VOAAF and 338 genes related to DILI identified, which were further analyzed in the IPA. The canonical pathway comparison showed that VOAAF and DILI both worked on aryl hydrocarbon receptor (AHR), lipopolysaccharide (LPS)/interleukin 1 (IL-1) mediated inhibition of retinoid X receptor (RXR) function, pregnane X receptor (PXR)/RXR activation, xenobiotic metabolism, peroxisome proliferator-activated receptor (PPAR), hepatic cholestasis, farnesoid X receptor (FXR)/RXR activation, and glucocorticoid receptor. CONCLUSION: VOAAF-induced liver injury may be involved in many pathways in which the AHR signaling and LPS/IL-1 mediated inhibition of RXR function pathways could be the most vital.

Effectiveness and safety of acupuncture combined with Madopar for Parkinson's disease: a systematic review with meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of acupuncture combined with Madopar for the treatment of Parkinson's disease (PD), compared to the use of Madopar alone. METHODS: A systematic search was carried out for randomised controlled trials (RCTs) of acupuncture and Madopar for the treatment of PD published between April 1995 and April 2015. The primary outcome was total effectiveness rate and secondary outcomes included Unified Parkinson's Disease Rating Scale (UPDRS) scores. Data were pooled and analysed with RevMan 5.3. Results were expressed as relative ratio (RR) with 95% confidence interval (CIs). RESULTS: Finally, 11 RCTs with 831 subjects were included. Meta-analyses showed that acupuncture combined with Madopar for the treatment of PD can significantly improve the clinical effectiveness compared with Madopar alone (RR=1.28, 95% CI 1.18 to 1.38, P<0.001). It was also found that acupuncture combined with Madopar significantly improved the UPDRS II (SMD=-1.00, 95% CI -1.71 to -0.29, P=0.006) and UPDRS I-IV total summed scores (SMD=-1.15, 95% CI -1.63 to -0.67, P<0.001) but not UPDRS I (SMD=-0.37, 95% CI -0.77 to 0.02, P=0.06), UPDRS III (SMD=-0.93, 95% CI -2.28 to 0.41, P=0.17) or UPDRS IV (SMD=-0.78, 95% CI -2.24 to 0.68, P=0.30) scores. Accordingly, acupuncture combined with Madopar appeared to have a positive effect on activities of daily life and the general condition of patients with PD, but was not better than Madopar alone for the treatment of mental activity, behaviour, mood and motor disability. In the safety evaluation, it was found that acupuncture combined with Madopar was associated with significantly fewer adverse effects including gastrointestinal reactions (RR=0.38, 95% CI 0.23 to 0.65, P<0.001), on-off phenomena (RR=0.27, 95% CI 0.11 to 0.66, P=0.004) and mental disorders (RR=0.24, 95% CI 0.06 to 0.92, P=0.04) but did not significantly reduce dyskinesia (RR=0.64, 95% CI 0.35 to 1.16, P=0.14). CONCLUSION: Acupuncture combined with Madopar appears, to some extent, to improve clinical effectiveness and safety in the treatment of PD, compared with Madopar alone. This conclusion must be considered cautiously, given the quality of most of the studies included was low. Therefore, more high-quality, multicentre, prospective, RCTs with large sample sizes are needed to further clarify the effect of acupuncture combined with Madopar for PD.

To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory.

Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p < 0.05), and the coefficient was 0.178 (p < 0.05); also they were related with five flavors (p < 0.05), and the coefficient was 0.145 (p < 0.05); they were not related with channel tropism (p > 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs.