1.A novel "target constituent knock-out" strategy coupled with TLC, UPLC-ELSD and microcalorimetry for preliminary screening of antibacterial constituents in Calculus bovis.
Kong WJ1, Wang JB, Zang QC, Jin C, Wang ZW, Xing XY, Wu YY, Zhao YL, Yang MH, Xiao XH. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 15;879(30):3565-73. doi: 10.1016/j.jchromb.2011.09.045. Epub 2011 Oct 1.
A novel "target constituent knock-out" strategy was proposed and applied for preliminary screening of antibacterial constituents in Calculus bovis (C. bovis). This strategy was accomplished through the following steps: (1) the single constituents (A-F) in C. bovis samples were knocked out on the Silica Gel thin-layer plates by thin-layer chromatography (TLC); (2) these knocked-out constituents were identified by ultra performance liquid chromatography-evaporative light scattering detection (UPLC-ELSD); (3) the antibacterial activities of these knocked-out constituents and C. bovis samples on Staphylococcus aureus (S. aureus) were evaluated by microcalorimetry combined with principal component analysis (PCA); (4) the activities of these knocked-out constituents and the total extract of C. bovis, also the interaction properties between these single constituents and the total extract were elucidated. The results showed that the sum of inhibitory ratio (I) of constituents A-F (202.
2.Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior.
Huang F1, Wang T1, Lan Y1, Yang L1, Pan W2, Zhu Y1, Lv B1, Wei Y1, Shi H1, Wu H1, Zhang B1, Wang J1, Duan X3, Hu Z1, Wu X1. Front Behav Neurosci. 2015 Mar 30;9:70. doi: 10.3389/fnbeh.2015.00070. eCollection 2015.
Farnesoid X receptor (FXR) is a nuclear hormone receptor involved in bile acid synthesis and homeostasis. Dysfunction of FXR is involved in cholestasis and atherosclerosis. FXR is prevalent in liver, gallbladder, and intestine, but it is not yet clear whether it modulates neurobehavior. In the current study, we tested the hypothesis that mouse FXR deficiency affects a specific subset of neurotransmitters and results in an unique behavioral phenotype. The FXR knockout mice showed less depressive-like and anxiety-related behavior, but increased motor activity. They had impaired memory and reduced motor coordination. There were changes of glutamatergic, GABAergic, serotoninergic, and norepinephrinergic neurotransmission in either hippocampus or cerebellum. FXR deletion decreased the amount of the GABA synthesis enzyme GAD65 in hippocampus but increased GABA transporter GAT1 in cerebral cortex. FXR deletion increased serum concentrations of many bile acids, including taurodehydrocholic acid, taurocholic acid, deoxycholic acid (DCA), glycocholic acid (GCA), tauro-α-muricholic acid, tauro-ω-muricholic acid, and hyodeoxycholic acid (HDCA).
3.Naturally occurring marine steroid 24-methylenecholestane-3β,5α,6β,19-tetraol functions as a novel neuroprotectant.
Leng T1, Liu A2, Wang Y2, Chen X3, Zhou S3, Li Q2, Zhu W2, Zhou Y2, Su X2, Huang Y2, Yin W2, Qiu P2, Hu H3, Xiong ZG4, Zhang J5, Yan G6. Steroids. 2016 Jan;105:96-105. doi: 10.1016/j.steroids.2015.11.005. Epub 2015 Nov 26.
Steroids have been shown to have multiple effects on the nervous system including neuroprotective activities, and they have the potential to be used for the treatment of neurodegenerative diseases. In this current study, we tested the hypothesis that the marine steroid 24-methylenecholestane-3β,5α,6β,19-tetraol (Tetrol) has a neuroprotective effect. (1) We synthesized Tetrol through a multiple step reaction starting from hyodeoxycholic acid (HDCA). (2) We then evaluated the neuroprotective effect of Tetrol with a glutamate-induced neuronal injury model in vitro. Tetrol concentration dependently increased the survival rate of cerebellar granule neurons challenged with toxic concentration of glutamate. Consistently, Tetrol significantly decreased glutamate-induced lactate dehydrogenase (LDH) release with a threshold concentration of 2.5μM. (3) We further evaluated the neuroprotective effect of Tetrol in a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia model in rat.
4.Organic anion-transporting polypeptide 1a4 (Oatp1a4) is important for secondary bile acid metabolism.
Zhang Y1, Csanaky IL, Selwyn FP, Lehman-McKeeman LD, Klaassen CD. Biochem Pharmacol. 2013 Aug 1;86(3):437-45. doi: 10.1016/j.bcp.2013.05.020. Epub 2013 Jun 6.
Organic anion transporting polypeptides (human: OATPs; rodent: Oatps) were thought to have important functions in bile acid (BA) transport. Oatp1a1, 1a4, and 1b2 are the three major Oatp1 family members in rodent liver. Our previous studies have characterized the BA homeostasis in Oatp1a1-null and Oatp1b2-null mice. The present study investigated the physiological role of Oatp1a4 in BA homeostasis by using Oatp1a4-null mice. Oatp1a4 expression is female-predominant in livers of mice, and thereby it was expected that female Oatp1a4-null mice will have more prominent changes than males. Interestingly, the present study demonstrated that female Oatp1a4-null mice had no significant alterations in BA concentrations in serum or liver, though they had increased mRNA of hepatic BA efflux transporters (Mrp4 and Ostα/β) and ileal BA transporters (Asbt and Ostα/β). In contrast, male Oatp1a4-null mice showed significantly altered BA homeostasis, including increased concentrations of deoxycholic acid (DCA) in serum, liver and intestinal contents.