Composition analysis and preliminary safety evaluation of edible Monascus red pigment

ObjectiveTo provide scientific basis for the development and utilization of edible pigment Monascus red， the analysis of its key components and toxicological evaluation were carried out.MethodsIdentification test and physicochemical indexes test were carried out based on the samples according to the method in National food safety standard GB 1886.181—2016. The content of citrinin （CIT） and Monacolin K were detected through high performance liquid chromatography （HPLC）. UPLC-Orbitrap-MS2 were used for chemical composition and content determination， in which the molecular structure was also characterized. The 14-day oral toxicity test of SD rats was carried out， based on the acute oral toxicity test of Monascus red by the limited method.ResultsThe quality and specification of test samples conformed to the provisions of China National Food Safety Standard. The content of CIT and Monacolin K was 0.030 8 mg/kg （converted as one color value） and 0.166 mg/g. Twenty compounds were separated in Monascus red by UPLC-Orbitrap-MS2， red pigment， orange pigment and yellow pigment of it accounted for 88.38%， 2.04% and 5.96%， respectively. The results of acute oral toxicity showed that Monascus red was innocuous （LD50>20 g/kg·BW）. In the 14-day repeated oral dose toxicity test， compared with the control group， rats in 5 g/kg·BW dose group exhibited no significant differences in the general clinical observation， growth and development， hematology， blood biochemistry， routine urine detection， gross anatomy，organ weight，organ-to-body ratio， and histopathological examinations.ConclusionMonascus red is composed of multiple components characterized by red pigments. There is no obvious toxic effects found in the preliminary safety evaluation， which can provide reference for further long-term research

Amiodarone-induced retinal neuronal cell apoptosis attenuated by IGF-1 via counter regulation of the PI3k/Akt/FoxO3a pathway

Amiodarone (AM) is the most effective antiarrhythmic agent currently available. However, clinical application of AM is limited by its serious toxic adverse effects including optic neuropathy. The purpose of this study was to explore the effects of AM and to assess if insulin-like growth factor-1 (IGF-1) could protect retinal neuronal cells from AM-induced apoptosis, and to determine the molecular mechanisms underlying the effects. Accordingly, the phosphorylation/activation of Akt and FoxO3a were analyzed by Western blot while the possible pathways involved in the protection of IGF-1 were investigated by application of various pathway inhibitors. The full electroretinogram (FERG) was used to evaluate in vivo effect of AM and IGF-1 on rat retinal physiological functions. Our results showed that AM concentration dependently caused an apoptosis of RGC-5 cells, while IGF-1 protected RGC-5 cells against this effect by AM. The protective effect of IGF-1 was reversed by PI3K inhibitors LY294002 and wortmannin as well as the Akt inhibitor VIII. AM decreased p-Akt and p-FoxO3a while increased the nuclear localization of FoxO3a in the RGC-5 cells. IGF-1 reversed the effect of AM on the p-Akt and p-FoxO3a and the nuclear translocation of FoxO3a. Similar results were obtained in primary cultured retinal ganglia cells. Furthermore, FERG in vivo recording in rats showed that AM decreased a-wave and b-wave of FERG while IGF-1 reversed the effects of AM. These data show that AM induced apoptosis of retinal neuronal cells via inhibiting the PI3K/Akt/FoxO3a pathway while IGF-1 protected RGC-5 cells against AM-induced cell apoptosis by stimulating this pathway