Synthesis and biological evaluation of tyrosine derivatives as peripheral 5HT2A receptor antagonists for nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), attributed to excessive fat accumulation in the liver, is reportedly prevalent worldwide. NAFLD is one of the leading causes of chronic liver disease, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatic cellular carcinoma (HCC). The peripheral roles of serotonin (5-hydroxytryptamine, 5HT) were found to regulate hepatic lipid metabolism. Among serotonin receptor subtypes, 5HT2A receptor is known to regulate hepatic lipid metabolism. Hepatic lipid accumulation and hepatic triglyceride (TG) were reduced in liver-specific 5HT2A receptor knockout (5HT2A receptor LKO) mice upon high-fat diet (HFD) feeding. In the present study, we explored a series of new peripherally acting 5HT2A receptor antagonists. Compound 14a displayed good in vitro activity, with an IC50 value of 0.17 nM. Compound 14a exhibited good microsomal stability, no significant CYP and hERG inhibition, and 5HT receptor subtype selectivity. The brain-to-plasma ratio of 14a was below the lower limit of quantification, indicating limited blood-brain barrier (BBB) penetration. HFD-fed 14a treated mice showed decreased liver steatosis and lobular inflammation. These results demonstrate the potential of newly synthesized peripheral 5HT2A receptor antagonists for treating NAFLD.

Baicalin attenuates fibrogenic process in human renal proximal tubular cells (HK-2) exposed to diabetic milieu.

AIMS: Baicalin, a flavonoid glycoside substance extracted from Scutellaria baicalensis Georgi, has been shown to exhibit multiple therapeutic properties owing to its anti-inflammatory effect. Diabetes is characterized by chronic hyperglycemia, inflammation and oxidative stress, which promote renal fibrosis and kidney failure. Although anti-fibrogenic effects of baicalin in lung and liver have been reported previously, no study has investigated its roles in renal fibrosis. Here, we demonstrated protective effects of baicalin against fibrogenic process in human kidney proximal tubular epithelial cells (HK-2) exposed to diabetic milieu. MAIN METHODS: To investigate the effects of baicalin on oxidative stress- and inflammation-induced fibrosis in HK-2 cells, protein and gene expressions of NF-κB- and STAT3-associated inflammatory molecules and TGFß-associated extracellular matrix proteins were examined by western blotting, immunocytochemistry and qRT-PCR. To determine physiological changes of HK-2 exposed to diabetic milieu in response to baicalin, production of cAMP and cGMP and Ca2+ influx were measured. KEY FINDINGS: Baicalin attenuated oxidative stress- and inflammation-inudced IκB and JAK2 phosphorylations and, subsequent, NF-κB nuclear translocation and STAT3 phosphorylation. Consequently, it markedly reduced transactivation of NF-κB- and STAT3-associated inflammatory genes such as ICAM1, VCAM1, TGFß, IL1ß and MCP1, and protein expression of TGFß-associated extracellular matrix proteins, such as fibronectin and collagen IV. These effects are, partially, attributed to its regulatory function of intracellular concentration of Ca2+ via interaction with type A γ-aminobutyric acid receptor. SIGNIFICANCE: This is the first study which investigated anti-fibrogenic effect of baicalin in human kidney cells, and our results highlight a potential therapeutic application of baicalin for diabetic nephropathy.

Enhanced photovoltaic performance of novel TiO2 photoelectrode on TCO substrates for dye-sensitized solar cells.

In this study, we report synthesis and growth of rutile-anatase TiO2 thin film on fluorine-doped tin oxide (FTO) glass by a two-step hydrothermal method. The effects of additional treatments (i.e., TiCl4 post-treatment and seed layer formation were also studied. Photocurrent-voltage (I-V) measurement of rutile-anatase TiO2 thin film was performed under 1.5 G light illumination. Photovoltaic performance was investigated by incident photon-to-electron conversion efficiency (IPCE), electrochemical impedance spectroscopy (EIS), intensity-modulated photocurrent/photovoltage spectroscopy (IMVS/IMPS) and open-circuit photovoltage decay (OCVD).

Molecular design and photovoltaic performance of organic dyes containing phenothiazine for dye-sensitized solar cells.

We synthesized novel organic photosensitizers based on fluorine-substituted phenothiazine with thiophene bridge units in the chromophore for application in dye-sensitized solar cells (DSSCs). Furthermore, organic dyes with different acceptors exhibited higher molar extinction coefficients, and better light absorption at longer wavelengths. The photovoltaic properties of organic dyes composed of different acceptors in their chromophores were measured to identify their effects on the DSSC performance. The organic dye, PFSCN2 containing multi-cyanoacrylic acid as the electron acceptor, showed a power conversion efficiency of 4.67% under AM 1.5 illumination (100 mW/cm2). The retarded recombination kinetics from TiO2 electrode to electrolyte enhanced the electron life time of the organic dye, PFSCN2 in the photoanode of the DSSC. This was confirmed with impedance analysis.