9R-10alpha-Hydroxyepigambogic acid

Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase.[Pubmed:28388410]

Cell. 2017 Apr 6;169(2):258-272.e17.

A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.

Critical Evaluation of NIR and ATR-IR Spectroscopic Quantifications of Rosmarinic Acid in Rosmarini folium Supported by Quantum Chemical Calculations.[Pubmed:28388786]

Planta Med. 2017 Aug;83(12-13):1076-1084.

The present study evaluates the analytical performance of near infrared as well as attenuated total reflection infrared spectroscopy for the determination of the rosmarinic acid content in Rosmarini folium. Therefore, the recorded near infrared and attenuated total reflection infrared spectra of 42 milled Rosmarini folium samples were correlated with reference data (range: 1.138-2.199 rosmarinic acid %) obtained by HPLC analysis. Partial least squares regression models were established as a quantitative multivariate data analysis tool. Evaluation via full cross-validation and test set validation resulted in comparable performances for both techniques: near infrared [coefficient of determination: 0.90 (test set validation); standard error of cross-validation: 0.060 rosmarinic acid %; standard error of prediction: 0.058 rosmarinic acid %] and attenuated total reflection infrared [coefficient of determination: 0.91 (test set validation); standard error of cross-validation: 0.063 rosmarinic acid %; standard error of prediction: 0.060 rosmarinic acid %]. Furthermore, quantum chemical calculations were applied to obtain a theoretical infrared spectrum of rosmarinic acid. Good agreement to the spectrum of pure rosmarinic acid was achieved in the lower wavenumber region, whereas the higher wavenumber region showed less compliance. The knowledge of the vibrational modes of rosmarinic acid was used for the association with the high values of the regression coefficient plots of the established partial least squares regression models.

Application of UV-irradiated Fe(III)-nitrilotriacetic acid (UV-Fe(III)NTA) and UV-NTA-Fenton systems to degrade model and natural occurring naphthenic acids.[Pubmed:28388447]

Chemosphere. 2017 Jul;179:359-366.

Naphthenic acids (NAs) are a highly complex mixture of organic compounds naturally present in bitumen and identified as the primary toxic constituent of oil sands process-affected water (OSPW). This work investigated the degradation of cyclohexanoic acid (CHA), a model NA compound, and natural occurring NAs during the UV photolysis of Fe(III)-nitrilotriacetic acid (UV-Fe(III)NTA) and UV-NTA-Fenton processes. The results indicated that in the UV-Fe(III)NTA process at pH 8, the CHA removal increased with increasing NTA dose (0.18, 0.36 and 0.72 mM), while it was independent of the Fe(III) dose (0.09, 0.18 and 0.36 mM). Moreover, the three Fe concentrations had no influence on the photolysis of the Fe(III)NTA complex. The main responsible species for the CHA degradation was hydroxyl radical (OH), and the role of dissolved O2 in the OH generation was found to be negligible. Real OSPW was treated with the UV-Fe(III)NTA and UV-NTA-Fenton advanced oxidation processes (AOPs). The removals of classical NAs (O2-NAs), oxidized NAs with one additional oxygen atom (O3-NAs) and with two additional oxygen atoms (O4-NAs) were 44.5%, 21.3%, and 25.2% in the UV-Fe(III)NTA process, respectively, and 98.4%, 86.0%, and 81.0% in the UV-NTA-Fenton process, respectively. There was no influence of O2 on the NA removal in these two processes. The results also confirmed the high reactivity of the O2-NA species with more carbons and increasing number of rings or double bond equivalents. This work opens a new window for the possible treatment of OSPW at natural pH using these AOPs.