1.Effects of Various 5,7-Dihydroxyflavone Analogs on Adipogenesis in 3T3-L1 Cells.
Nishina A1, Ukiya M, Fukatsu M, Koketsu M, Ninomiya M, Sato D, Yamamoto J, Kobayashi-Hattori K, Okubo T, Tokuoka H, Kimura H. Biol Pharm Bull. 2015;38(11):1794-800. doi: 10.1248/bpb.b15-00489.
We studied the effects of twelve 5,7-dihydroxyflavone analogs on adipogenesis in 3T3-L1 cells. Among the compounds, luteolin, diosmetin, and chrysoeriol partly inhibited adipogenesis by blocking the accumulation of triacylglycerol in the cells. Conversely, tricetin facilitated triacylglycerol accumulation in the cells. The induction of lipogenesis or lipolysis may depend on the number and bonding position of hydroxyl or methoxy groups on the B ring of 5,7-dihydroxyflavone. The mRNA expression levels of adipogenic and lipogenic genes were suppressed by luteolin treatment in the cells, while the mRNA levels of lipolytic genes were not affected. However, the expression levels of the adipogenic, lipogenic, and lipolytic genes, except for adipocyte protein 2 (aP2), were not affected by the addition of tricetin. Moreover, luteolin suppressed glucose transporter type 4 (GLUT4) gene and protein levels. These results indicate that luteolin decreased triacylglycerol levels in 3T3-L1 cells during adipogenesis through the suppression of adipogenic/lipogenic and GLUT4 genes and GLUT4 protein.
2.Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP‑2 and MMP‑9.
Liu J1, Wen X1, Liu B1, Zhang Q1, Zhang J1, Miao H1, Zhu R1. Mol Med Rep. 2016 Mar;13(3):2401-8. doi: 10.3892/mmr.2016.4872. Epub 2016 Feb 5.
Hepatocellular carcinoma (HCC) is one of the most malignant types of tumor worldwide with a high rate of mortality. Diosmetin (DIOS) exhibits various activities, including anticancer activities. However, the role of DIOS in the metastasis of HCC, and its underlying molecular mechanism, remain to be fully elucidated. In the present study, the antimetastatic effects of DIOS were investigated in SK‑HEP‑1 and MHcc97H HCC cell lines. Cell proliferation, wound healing, motility, invasion and adhesion capacities were examined to evaluate the inhibitory effect of DIOS on the metastasis of HCC cells. Cell viability was detected using an MTT assay in order to verify the inhibitory effect of DIOS on the proliferation of HCC cells. Cell migration was assessed using would healing and motility assays in order to verify the inhibitory effect of DIOS on the migration of HCC cells. Cell invasion and adhesion assays were performed in order to verify the inhibitory effect of DIOS on the invasion and adhesion of HCC cells.
3.Pharmacokinetic Profile of µSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats.
Russo R, Mancinelli A, Ciccone M, Terruzzi F, Pisano C, Severino L. Nat Prod Commun. 2015 Sep;10(9):1569-72.
Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (µSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t½), and relative oral bioavailability (%F).
4.Comparative Pharmacokinetics Study of Icariin and Icariside II in Rats.
Cheng T1, Zhang Y2, Zhang T3, Lu L4, Ding Y5, Zhao Y6. Molecules. 2015 Dec 1;20(12):21274-86. doi: 10.3390/molecules201219763.
To explore the pharmacokinetic properties of icariin (ICA) and icariside II (ICA II) following intragastric and intravenous administration in rats, a rapid and sensitive method by using ultra-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was developed and validated for the simultaneous quantification of ICA and ICA II in rat plasma. The quantification was performed by using multiple reaction monitoring of the transitions m/z 677.1/531.1 for ICA, 515.1/369.1 for ICA II and 463.1/301.1 for diosmetin-7-O-β-d-glucopyranoside (IS). The assay showed linearity over the concentration range of 1.03-1032 ng/mL, with correlation coefficients of 0.9983 and 0.9977. Intra- and inter-day precision and accuracy were within 15%. The lower limit of quantification for both ICA and ICA II was 1.03 ng/mL, respectively. The recovery of ICA and ICA II was more than 86.2%. The LC-MS/MS method has been successfully used in the pharmacokinetic studies of ICA and ICA II in rats.