The purpose of our research is to find a new lipid emulsion to deliver a low water-soluble compound, cinnamaldehyde (CA). Its characteristics, pharmacokinetics, antitumor efficacy, and toxicity were evaluated. The mean particle size, zeta potential, and encapsulation efficiency of the submicromemter emulsion of CA (SME-CA) were 130 ± 5.92 nm, −25.7 ± 6.00 mV, and 99.5 ± 0.25%, respectively. The area under the curve from 0 h to termination time (AUC0–t) of SME-CA showed a significantly higher value than that of CA (589 ± 59.2 vs 375 ± 83.5 ng h/L, P < 0.01). Tissue distribution study showed various changes; among them, a 27% higher concentration was found in brain tissue when using SME-CA at 15 min after administration. For the efficacy evaluation, SME-CA exhibited 8- and 11-fold antitumor activity in the depression of HeLa and A549 cell lines with the IC50 decreasing to 0.003 and 0.001 mmol/L, respectively. The LD50 values of CA and SME-CA in mice were 74.8 and 125 mg/kg, suggesting increased safety from the new formulation. The new formulation exhibited lower toxicity, higher antitumor activity, and a more satisfactory pharmacokinetic property, which displayed great potential for future pharmacological application.

•A new method is described to simultaneously quantify cinnamaldehyde and its metabolites.•The pharmacokinetic parameters of cinnamaldehyde and its metabolites are determined.•A new metabolite methyl cinnamate was determined.•Pharmacokinetic study showed that a small portion of cinnamaldehyde sustained a low concentration for a long time.A selective and sensitive method utilizing gas chromatography–mass spectrometry was developed for simultaneous determination of cinnamaldehyde, cinnamyl alcohol, and methyl cinnamate in rat plasma. Cinnamaldehyde and cinnamyl alcohol can inter-convert to one another in rats, thus simultaneous quantifying both analytes provided a reliable and accurate method of assessment. Three qualifying ions (131 m/z, 105 m/z and 92 m/z) were chosen for simultaneous quantification of cinnamaldehyde and its metabolites. In this study, the calibration curves demonstrated a good linearity and reproducibility over the range of 20–2000 ng/ml (r2 ≥ 0.999) for all analytes. Furthermore, the sensitivity of gas chromatography–mass spectrometry revealed sufficient lower limit of quantitation and detection of 20 ng/ml and 5 ng/ml, respectively, in the pharmacokinetic analysis. The intra- and inter-day precision variations were less than 10.4% and 12.2%, respectively, whilst accuracy values ranged from −8.6% to 14.8%. All analytes were stable in plasma and in processed samples at room temperature for 24 h with no significant degradation after three freeze/thaw cycles. A small amount of the administered cinnamaldehyde had long half-life of 6.7 ± 1.5 h. In this study, gas chromatography–mass spectrometry was demonstrated to be a powerful tool for the pharmacokinetic studies of rats after intravenous and oral administration of cinnamaldehyde.

•A pectin-coated liposomal formulations was prepared by forming an ion-complex.•The pectin-coated liposome has an excellent stability and mucoadhesiveness properties.•The pectin-coated liposome would be a promising drug carrier system for colon cancer.The aim of this study was to investigate the potential effect of pectin for liposomal drug delivery systems. An orthogonal L9 (33) test was designed to optimize the preparation condition of cationic bufalin liposomes coated with commercially available citrus pectin (CPL). The change in particle size, zeta potential, entrapment efficiency, stability, mucoadhesion and anticancer effect were evaluated. The results showed that CPL had an excellent stability and mucoadhesive properties, and the drug release in vitro was modest prolonged and sustained. Furthermore, the inhibition effect of liposomes on SW480 colon cancer cells was dramatic enhanced due to a block of cell cycle at G0/G1 phase, and CPL had a higher inhibition rate than bufalin liposomes (BFL) because of the anticancer effect of citrus pectin. It is concluded that CPL is a potentially promising drug carrier system treatment for colon cancer.

Imperatorin (IMP) is a biologically active ingredient isolated from a traditional Chinese medicine (TCM), Angelica dahurica. To obtain the brain distribution data of IMP in rats, the concentrations of IMP in cortex, cerebellum, diencephalon, brain stem, striatum and hippocampus were measured by a simple and sensitive HPLC–UV method. The analytes were prepared by a liquid–liquid extraction method and the separation of IMP was performed on a Hypersil BDS C18 column (250 mm × 4.6 mm i.d., 5 μm) using acetonitrile–water (60:40, v/v) as mobile phase which was delivered at 1.0 mL min−1. Ultraviolet detection was performed at 300 nm. Using a weighted (1/c2) least square method, linear calibration curves for the six regions were obtained (r ≥ 0.9990) with a lower limit of quantification (LLOQ) of 0.075 μg g−1 for cortex, cerebellum, diencephalon and brain stem or 0.15 μg g−1 for striatum and hippocampus, and the recovery was greater than 90% for each tissue sample. The within- and between-day precisions (expressed as the relative standard deviation, RSD) were less than 10%. The validated method has been successfully applied to the brain distribution study in rats. The results showed that IMP could pass through the blood–brain barrier easily. And the higher concentration in striatum and hippocampus compared with the others might indicate that they were the target regions of IMP in rat brain.

Early experiments showed cinnamaldehyde had obvious therapeutic effect on viral myocarditis, but cinnamaldehyde was unstable in vivo. To overcome this limitation, we used cinnamaldehyde as a lead compound to synthesize α-bromo-4-chlorocinnamaldehyde (BCC). In the present study, we compared the therapeutic effects of BCC with cinnamaldehyde on coxsackie virus B3 (CVB3)-induced viral myocarditis (VMC), as well as investigated the possible mechanism. The antiviral and cytotoxic effects in vitro were evaluated on HeLa cells infected by CVB3 and rat cardiomyocytes respectively. Our results showed that IC50 were 0.78 ± 0.13 μM and 48.16 ± 5.79 μM in BCC and cinnamaldehyde-treated cells. 50% toxic concentration (TC) in BCC-treated cells was 22-fold higher than in the cinnamaldehyde group. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. The results demonstrated that BCC reduced the viral titers and cardiac pathological changes in a dose-dependent manner. Myocardial virus titers were significantly lower in the 50 mg/kg BCC-treated group than in cinnamaldehyde groups. In addition, BCC could significantly inhibit the replication of CVB3 mRNA and the secretion of inflammatory cytokines TNF-α, IL-β and IL-6 in CVB3-infected cardiomyocytes. We further observed that BCC suppressed CVB3-induced NF-κB activation, IκB-α degradation and phosphorylation in a concentration-dependent manner, and reduced Toll like receptor (TLR) 4 protein level in hearts. These results suggest that BCC had a promising therapeutic effect on VMC with a highly significant favorable effects and less toxicity than cinnamaldehyde. Furthermore, the effect of BCC on VMC might be through inhibition of inflammatory signaling.Highlights► We compared the therapeutic effects of α-bromo-4-chlorocinnamaldehyde (BCC) with cinnamaldehyde on viral myocarditis (VMC). ► BCC inhibited coxsackie virus B3 replication and cardiac injury in vitro and in vivo. ► The effect of BCC on VMC might be through inhibition of inflammatory signaling. ► These results suggest that BCC had a promising therapeutic effect on VMC.