A self-contrast approach to evaluate the inhibitory effect of chrysosplenetin, in the absence and presence of artemisinin, on the in vivo P-glycoprotein-mediated digoxin transport activity.

In this study, we used a self-contrast method, which excluded the individual difference, to evaluate the inhibitory effect of chrysosplentin (CHR) in the presence or absence of artemisinin (ART) on the P-glycoprotein (P-gp) transport activity. A sensitive and rapid UHPLC-MS/MS method was applied for quantification of digoxin, a P-gp-specific substrate, in rat plasma. A pharmacokinetic study was carried out: first after an oral administration of digoxin at a dose of 0.09 mg/kg (first period), followed by a 20-day wash-out, then after another administration of digoxin (second period). During the second period, test compounds were orally given three times per day for seven consecutive days. Results showed that the t1/2 of digoxin in all the groups had no significant difference between the first and second periods. The AUC0-24 , Cmax , tmax , and Clz /F of the negative control and ART alone groups showed no difference. However, the AUC0-24 and Cmax in the CHR alone, CHR-ART (1:2) and verapamil (positive control) groups showed 2.34-, 3.04-, 1.79-, and 1.81-, 1.99-, 2.06-fold increases along with 3.50-, 3.84- and 4.76-fold decreases for CLz /F, respectively. The tmax in the CHR-ART (1:2) group increased 3.73-fold. In conclusion, our self-contrast study suggested that CHR, especially when combined with ART in a ratio of 1:2, inhibited P-gp activity while ART alone has no effect. Copyright © 2016 John Wiley & Sons, Ltd.

A new periplogenin cardenolide from the seeds of Antiaris toxicaria.

A new periplogenin cardenolide, periplogulcoside (1), together with three known cardenolides, was isolated from the seeds of Antiaris toxicaria. The structure of the new compound was characterized as periplogenin-3-O-ß-D-glucopyranosyl-(1 → 4)-ß-D-glucopyranoside (1) by spectroscopic methods including 1D and 2D NMR, HR-TOF-MS, and CD spectrometry, and the known compounds were identified by comparison of their NMR and HR-TOF-MS data with those reported in the literature. Compound 1 showed significant cytotoxicity against Hela and HepG-2 cell lines.

Agreement of intraocular pressure measurement with Corvis ST, non-contact tonometer, and Goldmann applanation tonometer in children with ocular hypertension and related factors.

AIM: To access the agreement of intraocular pressure (IOP) values obtained from biomechanically corrected tonometer [Corvis ST (CST)], non-contact tonometer (NCT), and Goldmann applanation tonometer (GAT) in children with NCT measured-IOP (NCT-IOP) values of 22 mm Hg or more, and related factors. METHODS: A total of 51 eyes with NCT-IOP≥22 mm Hg in children aged 7 to 14y were examined and IOP was measured by CST, NCT, and GAT. Based on GAT measured IOP (GAT-IOP), ocular hypertension (OHT) group (≥22 mm Hg, 24 eyes) and the non-OHT group (<22 mm Hg, 27 eyes) were defined. We compared the agreement of the three measurements, i.e., CST measured IOP (CST-IOP), GAT-IOP, and NCT-IOP, and further analyzed the correlation between the differences in tonometry readings, central corneal thickness (CCT), axial length (AL), optic disc rim volume, and age. RESULTS: Compared with the OHT group, thicker CCT, larger rim volume, and higher differences between NCT-IOP and GAT-IOP, were found in the non-OHT group. The differences between CST-IOP and GAT-IOP were lower than the differences between NCT-IOP and GAT-IOP in both groups. The mean differences in CST-IOP and GAT-IOP were 1.26 mm Hg (95% limit of agreement ranged from 0.1 to 2.41 mm Hg, OHT group) and 1.20 mm Hg (95% limit of agreement ranged from -0.5 to 3.00 mm Hg, non-OHT group), and the mean differences in NCT and GAT were 3.90 mm Hg (95% limit of agreement ranged from -0.19 to 9.70 mm Hg, OHT group) and 6.00 mm Hg (95% limit of agreement ranged from 1.50 to 10.50 mm Hg, non-OHT group). The differences between CST-IOP and GAT-IOP were not related to CCT, age, and AL in both groups; while the differences between NCT-IOP and GAT-IOP were related to CCT in the OHT group (r=0.93, P<0.001) and to CCT and AL in the non-OHT group (r=0.66, P<0.001, r=-0.81, P<0.001). CONCLUSION: The accuracy of NCT in the diagnosis of pediatric OHT is low. The agreement of CST-IOP and GAT-IOP was significantly higher in children with and without OHT than in those with NCT-IOP and GAT-IOP. Therefore, CST can be used as a good alternative for IOP measurement in children. The impacts of CCT and AL on NCT measurement need to be fully considered when managing childhood IOP.

Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT, Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats.

Yu Gan Long (YGL) is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor (TGF-ß) in the previous study. But the mechanisms associated with platelet-derived growth factor (PDGF)-BB remain obscure. In this study, we further investigated the mechanism of YGL reducing carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV (Col IV), type HI precollagen (PCHI), hyaluronuc acid (HA) and laminin (LN), which are implicated in liver fibrosis. Also, YGL reduced the α-smooth muscle actin (α-SMA) expression, which acts as the indicator of liver fibrosis. Furthermore, YGL decreased the serum levels of hepatic stellate cell (HSC) mitogen PDGF-BB and inflammation cytokines, including TNF-α, IL-1ß, IL-6. Markers involved in liver fibrosis, such as Ras, p-Raf-1, p-ERK1/2, p-JNK, p-P38, p-PI3K, p-AKT, p-JAKl, p-STAT3 were downregulated significantly after treatment with YGL. Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production, and suppressing Ras/ERK, PI3K/AKT, and JAK1/STAT3 signaling pathways, which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.