Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism.

We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 µM (IC50 = 103 ± 2 µM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the KI and KIS inhibition constants to be 117.07 µM and 423.63 µM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug.

Chemical Composition and Antioxidant Activity of Essential Oil of Chinese Propolis.

The chemical composition and in vitro antioxidant activity of the essential oil of propolis (EOP) collected from 25 locations in China was investigated. Steam-distillation extraction was used to extract the EOP, and chemical composition was identified by GC/MS. The antioxidant activities of EOP were also measured. The result showed that a total of 406 compounds were detected in EOP. The major compounds of Chinese EOP were cedrol, γ-eudesmol, benzyl alcohol, phenethyl alcohol, 2-methoxy-4-vinylphenol, 3,4-dimethoxystyrene and guaiol. Principal component analysis revealed the significant correlation between EOP compositions and their origins, and certain correlation was detected between EOP and their color. Linear discriminant analysis showed that 88 % and 84 % of the propolis samples were predicted correctly as the groupings identified by climatic zone and the color, respectively. Furthermore, the differences of antioxidant activities of EOP were significant. EOP of Shandong had the strongest antioxidant activities, whereas EOP of Guangdong, Yunnan and Hunan showed the poorest.

MicroRNA-873 Inhibits Morphine-Induced Macrophage Apoptosis by Elevating A20 Expression.

OBJECTIVES: To study the role of microRNA-873 (miR-873) in suppressing morphine-induced macrophage apoptosis and morphine dependence, and to identify molecular targets within the miR-873 pathway for the treatment of immune suppression and morphine addiction. METHODS: As morphine elevates TLR9 expression and induces TLR9-mediated apoptosis, we used TLR9 knockout Balb/C mice to study TLR9-independent effects of miR-873 on morphine-induced macrophage apoptosis. Forty TLR9-knockout mice were randomly and equally assigned to morphine group and control group. Following the administration of morphine, miR-873 mimics or miR negative control was injected into mice in each group. Using freshly isolated macrophages from mice and RAW264.7 murine macrophage cell line, miR-873 level was determined by qRT-PCR and morphine induced apoptosis was measured by TUNEL assays. Western blotting was used to detect and quantify the expression level of A20, a protein that negatively regulates inflammation and TNF-induced apoptosis. RESULTS: qRT-PCR analysis revealed a markedly lower expression of miR-873 in freshly isolated peritoneal macrophages, liver tissue and spleen tissue in the morphine group compared with the corresponding tissues in the control group. TUNEL assays showed that the apoptosis rates in the morphine groups treated with miR-873 mimics was markedly lower than their respective control groups. Western blotting results showed that A20 expression level was sharply elevated in the experimental groups treated with miR-873 mimics than the negative and blank control groups. CONCLUSIONS: Our results show that miR-873 elevates A20 levels and inhibits morphine-induced macrophage apoptosis.