Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice.

1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters. 2. In vitro uptake tests showed that jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 µM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1-1 µM (for OCT2 and OCT3) and 1-10 µM (for PMAT). 3. In mouse synaptosomes, jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant. 4. The antidepressant-like action of jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of jatrorrhizine (5, 10 and 20 mg/kg, i.p.) or venlafaxine (20 mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group. 5. The concentration of jatrorrhizine shows a dose-dependent increase in brain tissues. 6. Our study suggested that jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters.

Efficient Solar-Driven Hydrogen Transfer by Bismuth-Based Photocatalyst with Engineered Basic Sites.

Photocatalytic organic conversions involving a hydrogen transfer (HT) step have attracted much attention, but the efficiency and selectivity under visible light irradiation still needs to be significantly enhanced. Here we have developed a noble metal-free, basic-site engineered bismuth oxybromide [Bi24O31Br10(OH)δ] that can accelerate the photocatalytic HT step in both reduction and oxidation reactions, i.e., nitrobenzene to azo/azoxybenzene, quinones to quinols, thiones to thiols, and alcohols to ketones under visible light irradiation and ambient conditions. Remarkably, quantum efficiencies of 42% and 32% for the nitrobenzene reduction can be reached under 410 and 450 nm irradiation, respectively. The Bi24O31Br10(OH)δ photocatalyst also exhibits excellent performance in up-scaling and stability under visible light and even solar irradiation, revealing economic potential for industrial applications.

Estradiol reduced 5-HT reuptake by downregulating the gene expression of Plasma Membrane Monoamine Transporter (PMAT, Slc29a4) through estrogen receptor ß and the MAPK/ERK signaling pathway.

Estrogen deficiency-induced female depression is closely related to 5-hydroxytriptamine (5-HT) deficiency. Estradiol (17ß-estradiol, E2) regulates the monoamine transporters and acts as an antidepressant by affecting 5-HT clearance through estrogen receptors and related signaling pathways at the genomic level, although the specific mechanisms require further exploration. The brain expresses higher levels of plasma membrane monoamine transporter (PMAT, involved in 5-HT reuptake of the uptake 2 system) than other uptake transporters. In this study, we found that estrogen-deficient ovariectomized (OVX) rats had high PMAT mRNA and protein expression levels in the hippocampus and estradiol significantly reduced these levels. Furthermore, estradiol inhibited PMAT expression and reduced 5-HT reuptake in neurons and astrocytes and estradiol regulated the PMAT expression mainly by affecting estrogen receptor ß (ERß) at the genomic level in astrocytes. Further experiments showed that estradiol also regulated PMAT expression through the MAPK/ERK signaling pathway and not through the PI3K/AKT signaling pathway. In conclusion, estradiol inhibited 5-HT reuptake by regulating PMAT expression at the genomic level through ERß and the MAPK/ERK signaling pathway, highlighting the importance of PMAT in the antidepressant effects of estradiol through 5-HT clearance reduction.

Dehydrocorydaline induced antidepressant-like effect in a chronic unpredictable mild stress mouse model via inhibiting uptake-2 monoamine transporters.

Dehydrocorydaline, is an active alkaloid compound in Corydalis yanhusuo W. T. Wang. We found dehydrocorydaline induced antidepressant-like effects in a chronic unpredictable mild stress mouse model, but the exact mechanisms have not been addressed. We speculated that dehydrocorydaline may have an antidepressant effect via inhibiting monoamine transporters in the brain. We evaluated the mechanism of action of dehydrocorydaline by examining the levels of monoamine transmitters (5-HT, NE and DA) in the prefrontal cortex in chronic unpredictable mild stress mice. Then, we used cell models and the mouse synaptosome to study molecular and cellular mechanisms underlying these behaviors and monoamine alterations by dehydrocorydaline. Our results indicated that dehydrocorydaline affects the concentrations of monoamine transmitters and decreases the turnover ratio, which indicates increased neuronal activity. The possible mechanism is that dehydrocorydaline potently inhibits uptake-2 transporters with the IC50 values of 0.1-4 µM and could inhibit the reuptake of 5-HT/DA/NE in the synaptosome. These data suggest that dehydrocorydaline has an antidepressant effect that is likely related to changing the content of monoamines in the brain by inhibiting uptake-2 transporters.

Ruthenium(II)-catalyzed regioselective reductive coupling of α-imino esters with dienes.

A method for the highly regioselective reductive coupling reaction of N-aryl-α-imino esters with dienes is described. The method utilizes the RuHCl(CO)(PPh3)3/iPrOH catalytic system under an Ar atmosphere and provides α-branched allylic α-amino acid derivatives. Application of this transformation to the concise synthesis of a natural plant growth regulator is demonstrated.

Cu(II)-catalyzed intermolecular amidation of C-acylimine: a convenient access to gem-diamino acid derivatives.

C-Acylimines 1 undergo intermolecular amidation with amides 2 to produce monoacyl gem-diamino acid derivatives 3 upon treatment with Cu(OTf)(2) (20 mol%)/ PPh(3) (20 mol%) under mild conditions. This method provides an efficient access to gem-diamino acid equivalents with good to excellent yields.