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Abstract: As biomarkers, endogenous neurotransmitters play critical roles in the process of neuropsychiatric diseases, and neurotransmitter levels in different brain regions can contribute to neurological disease diagnosis and treatment. Due to the lack of a blank matrix for endogenous neurotransmitters, surrogate‐matrix and surrogate‐analyte approaches have been used for the determination of neurotransmitters to solve this problem. In this study, we capitalised on the high accuracy, precision, and throughput of UHPLC‐MS/MS and developed new methods based on the two approaches. Both approaches satisfied FDA and EMA validation criterias after an appropriate parallelism assessment, and they were used to further quantify the three endogenous neurotransmitters, including dopamine (DA), serotonin (5‐HT) and γ‐aminobutyric acid (GABA) in rat brain four regions (cortex, striatum, hypothalamus and hippocampus) which represent the catecholamines, indolamines, and amino acids, respectively. Comparison of the results in the same rats (n = 10) showed there was no significant difference in DA, 5‐HT, or GABA levels between the two approaches (P > 0.05). The concentrations of DA and GABA were highest in striatum and hypothalamus, respectively, and the levels of 5‐HT were paralleled in striatum and hippocampus almost 2‐fold higher than other regions. This is the first study to compare these two approaches in the determination of endogenous neurotransmitter content in the rat brain, and the surrogate‐matrix approach proved to be simple, rapid, and reliable, considering cost, matrix similarity, and practicality. [ABSTRACT FROM AUTHOR]

• Eight labdane diterpenoids, including two new ones, were isolated from the fruits of Forsythia suspensa. • The absolute structures of two new labdane diterpenoids were determined by single crystal X-ray diffraction analysis and ECD data. • Eight labdane diterpenoids showed anti-inflammatory, with the inhibition rates of release of β -glucuronidase from polymorphonuclear leukocytes of rats being in the range 46.8–51.0%. • Eight labdane diterpenoids showed anti-viral activities against influenza A (H1N1) virus with the IC 50 values in the range 18.4–26.2 μM, and against respiratory syncytial virus (RSV) with the EC 50 values in the range 10.5–14.4 μM. Eight labdane diterpenoids, including two new labdane diterpenoids, named forsyshiyanins A-B (2 – 3), along with six known ones (1 , 4 – 8), were isolated from the fruits of Forsythia suspensa. The new structures including their absolute configurations were elucidated by extensive spectroscopic analyses, X-ray diffraction and computational calculation. In vitro , eight labdane diterpenoids showed anti-inflammatory activities, with the inhibition rates of release of β -glucuronidase from polymorphonuclear leukocytes of rats being in the range 46.8–51.0% at concentrations of 10 µM, as well as anti-viral activities against influenza A (H1N1) virus and respiratory syncytial virus (RSV), with the IC 50 values in the range 18.4–26.2 μM and EC 50 values in the range 10.5–14.4 μM, respectively. [ABSTRACT FROM AUTHOR]

This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased. Brain water contents and Evans blue extravasation of the right basal ganglia in the ICH group were augmented, and significantly reduced by escin. Escin abated the increases of monocyte counts and serum IL-1β levels induced by ICH. IL-1β administration reversed the effect of escin on Garcia test scores, the brain water contents, and the Evans blue extravasation. Escin ameliorated the increasing levels of RhoA, ROCK1, nuclear NF-κB and the decreasing expression of IκBα, cytosolic NF-κB, occludin, claudin-5 in the ICH group. IL-1β administration blocked not only escin-mediated increases of IκBα, cytosolic NF-κB, occludin, and claudin-5, but also escin-caused decreases of RhoA, ROCK1, and nuclear NF-κB. The results indicate that escin improves neurological outcomes and the BBB function in ICH mice, which is associated with attenuating ICH-induced peripheral system inflammation, and therefore, inhibiting IL-1β/RhoA/NF-κB signaling pathway in BBB, at least in part. These findings suggest that it may be useful to ameliorate brain injury by inhibiting systemic inflammation instead of aiming to target the brain directly after ICH. Unlabelled Image • Escin improves neurological function. • Escin ameliorates blood brain barrier impairment. • Escin inhibits systemic inflammation. [ABSTRACT FROM AUTHOR]