Spectrum-effect relationship between UHPLC-Q-TOF/MS fingerprint and promoting gastrointestinal motility activity of Fructus aurantii based on multivariate statistical analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, gastrointestinal motility disorders (GMD) have reduced the quality of people's daily life worldwide, but there is still a lack of effective western medicine treatment. Fructus aurantii (FA), a representative regulating-qi herbal medicine, has been widely used to treat GMD in China for thousands of years, but it is not clear that which specific components contribute to the efficacy. AIM OF THE STUDY: The efficacy differences of various fractions of FA on normal mice and GMD rats were compared, so as to find out the main effective fraction of FA, and to screen the main regulating-qi components based on spectrum-effect relationship and multivariate statistical analysis. MATERIALS AND METHODS: The fingerprints of different fractions of FA were established and main compounds were identified with UHPLC-Q-TOF/MS technique. The promoting gastrointestinal motility activities of FA were evaluated by defecation test, gastric emptying and intestinal propulsion test in mice, and further investigated according to the biochemical analysis of 5-HT, SP, MLT, GAS and VIP in GMD rats' plasma. One-way ANOVA was used to find out the difference of efficacy. The active components were screened through spectrum-effect relationship with PCA-X, Pearson bivariate correlation analysis and OPLS analysis. CONCLUSIONS: Ethyl acetate fraction is the main active fraction, and nine compounds are the major regulating-qi components. The developed spectrum-effect analysis can be used for the screening of bioactive components in natural products with high accuracy and reliability.

CXCR1 expression predicts benefit from tyrosine kinase inhibitors therapy in patients with metastatic renal cell carcinoma.

PURPOSE: CXCR1 signaling promotes tumor progression in various cancers, and clinical trial has proved efficacy of CXCR1 inhibitor in metastatic breast cancer. Therefore, we investigated the prognostic value of CXCR1 in patients with metastatic renal cell carcinoma (mRCC) receiving tyrosine kinase inhibitors (TKIs) therapy. MATERIALS AND METHODS: Patients treated with sunitinib or sorafenib were retrospectively enrolled (n = 111). CXCR1 expression was assessed by immunohistochemical staining of tissue microarrays of primary tumor, and its association with prognosis and therapeutic response were evaluated. To explore possible mechanism related to CXCR1 expression, gene set enrichment analysis was performed based on The Cancer Genome Atlas cohort. RESULTS: High CXCR1 expression was associated with poorer overall survival (P = 0.015) and was an independent prognostic factor for patients with mRCC treated by TKIs (Hazard Ratio = 1.683, 95% Confidence Interval: 1.109-2.553, P = 0.014). CXCR1 expression was also associated with worse therapeutic response of TKIs (P = 0.017). Thirteen pathways, including hypoxia and angiogenesis, were identified to be enriched in CXCR1 positive patients. CONCLUSIONS: High CXCR1 expression indicates reduced benefit from TKIs therapy in patients with mRCC. The mechanism may be attributed to the enriched pathways of hypoxia and angiogenesis in CXCR1 positive patients. CXCR1 may be a potential therapeutic target for mRCC, but further studies are required.

Cytotoxicity of naturally occurring rhamnofolane diterpenes from Jatropha curcas.

Twelve rhamnofolane diterpenoids, including curcusecons A-E with unusual seco-rhamnofolane skeletons, curcusones F-J, 4-epi-curcusone E, and 3-dehydroxy-2-epi-caniojane, together with seven known analogues, curcusones A-E, jatrogrossidione, and 2-epi-jatrogrossidione, were isolated from the roots of Jatropha curcas. Their structures were determined by extensive spectroscopic methods, and the relative stereochemistry of curcusecon B was further confirmed by X-ray crystallographic data. Their cytotoxity against five human cancer cells was studied and the results indicated that the dienone system in ring B was essential for cytotoxicity of these compounds.

New eudesmenoic acid methyl esters from the seed oil of Jatropha curcas.

Three new eudesmenoic acid methyl esters (1-3), as well as five known compounds, including three germacranolides (4-6) and two eudesmanolides (7 and 8), were isolated from the seed oil of Jatropha curcas. The new compounds were elucidated by means of spectroscopic methods, including extensive NMR spectra. In addition, the structure of 8 was confirmed by a single-crystal X-ray diffraction analysis. Among the isolates, compounds 4-6 were the first reported from the genus Jatropha. Using MTS viability assay, the cytotoxicity of compounds 2-8 were evaluated against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines. Compounds 4 and 5 showed remarkable cytotoxicity against all the tested cell lines with IC50 values from 0.5 to 3.5 µM, and the new compound 3 displayed selective cytotoxic activity against A-549 cell with an IC50 value of 7.24 µM, but slight cytotoxicity against HL-60 and MCF-7 with IC50 values of 23.77 and 22.37 µM, respectively.