ABSTRACT
The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.
Subject(s)
Animals , Humans , Mice , Rats , Cytokines , HeLa Cells , Interleukin-6 , Myocarditis , Myocytes, Cardiac , RNA, Messenger , Therapeutic UsesABSTRACT
BACKGROUND: Angelica sinensis is a famous traditional Chinese medicinalherb, which is predominantly used in the treatment of gynecological conditions. It is the first report for the simultaneous determination of six major active components in Chinese Angelica, which is important for quality control. OBJECTIVE: A validated HPLC-PAD method was first developed to evaluate the quality of crude and processed Radix Angelica through simultaneous determination of six bioactive compounds, namely ferulic acid, senkyunolide I, senkyunolide H, coniferyl ferulate, Z/E-ligustilide and Z/E-butylidenephthalide. MATERIALS AND METHODS: Samples were separated on a Xtimate™C18 column (250 × 4.6 mm, 5 µm) and detected by PAD. Mobile phase was composed of (A) aqueous phosphoric acid (0.02%, v/v) and (B) acetonitrile (MeCN) (including 10% tetrahydrofuran, v/v) using a gradient elution. Analytes were performed at 30°C with a flow rate of 1.0 mL/min. RESULTS: All calibration curves showed good linear regression (r(2) ≥ 0.9963) within the tested ranges, and the recovery of the method was in the range of 91.927-105.859%. CONCLUSION: The results demonstrate that the developed method is accurate and reproducible and could be readily utilized as a suitable quality control method for the quantification of Radix Angelica.
ABSTRACT
Objective To determine oleanolic acid(OA)and ursolic acid(UA)from Fructus Ligustri Lucidi in diffrernt habitat and various growing stages.Method We picked the fruits of Fructus Ligustri Lucidi in Otober in five cities of Shanxi,and in August,September,October,November and December in Xi'an.Removed impurities and storaged the fruits under room temperature.By HPLC with Waters 600 as its chromatographic system,and Lichrospher C_(18)(4.6mmx250mm,5?m) column was applied with CH_3CN-CH_3OH-H_2O-H_3PO_4-(C_2H_5)_3N(50:30:20:0.02:0.04)as its mobile phase,the flow rate was 1 mL/min.The standard working curve was made to determine the contents of OA and UA at different habitat and different time spot from samples.Result The contents of OA and UA were highest in Ankang city.During prolonging growing stages,the highest contents of OA and UA were October and August,respectively.They both reduced to the lowest point in December.Conclusion The contents of OA and UA changed in different habitat and diffrernt growing stages of Fructus Ligustri Lucidi. It was suggested that we should mainly base on the highest contents to select the harvest time according to our demands.
ABSTRACT
<p><b>AIM</b>To study the pharmacokinetics of genistein at different doses in Beagle dogs.</p><p><b>METHODS</b>Suspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.</p><p><b>RESULTS</b>The plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.</p><p><b>CONCLUSION</b>Due to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.</p>
