Synergic versus Antagonist Effects of Rutin on Gallic Acid or Coumarin Incorporated into Chitosan Active Films: Impacts on Their Release Kinetics and Antioxidant Activity.

This work deals with the study of the release and antioxidant activity kinetics of three natural antioxidants associated as binary mixture (coumarin, and/or gallic acid and rutin) from chitosan films. Antioxidants were incorporated into film alone or in binary mixture. The aim was to determine the influence of rutin on the phenolic acid and benzopyrone. The UV-visible light transmission spectra of the films were also investigated. Neat chitosan films and chitosan incorporated coumarin exhibited high transmittance in the UV-visible light range, while GA-added chitosan films showed excellent UV light barrier properties. The molecular interactions between chitosan network and antioxidants were confirmed by FTIR where spectra displayed a shift of the amide-III peak. Rutin has a complex structure that can undergo ionization. The chitosan network structure induced change was found to influence the release behavior. The film containing rutin showed the highest antioxidant activity (65.58 ± 0.26%), followed by gallic acid (44.82 ± 3.73%), while coumarin displayed the lowest activity (27.27 ± 4.04%). The kinetic rate against DPPH-free radical of rutin is three times higher than coumarin. The kinetic rates were influenced by the structure and interactions of the antioxidants with chitosan. Rutin exhibited a slow release due to its molecular interactions with chitosan, while coumarin and gallic acid showed faster release. The diffusion coefficient of coumarin is 900 times higher than that of rutin. The rutin presence significantly delayed the release of the gallic acid and coumarin, suggesting an antagonistic effect. However, their presence weakly affects the release behavior of rutin.

Influence of Surface Corona Discharge Process on Functional and Antioxidant Properties of Bio-Active Coating Applied onto PLA Films.

PLA (polylactic acid) is one of the three major biopolymers available on the market for food packaging, which is both bio-based and biodegradable. However, its performance as a barrier to gases remains too weak to be used for most types of food, particularly oxygen-sensitive foods. A surface treatment, such as coating, is a potential route for improving the barrier properties and/or providing bioactive properties such as antioxidants. Gelatin-based coating is a biodegradable and food-contact-friendly solution for improving PLA properties. The initial adhesion of gelatin to the film is successful, both over time and during production, however, the coating often delaminates. Corona processing (cold air plasma) is a new tool that requires low energy and no solvents or chemicals. It has been recently applied to the food industry to modify surface properties and has the potential to significantly improve gelatin crosslinking. The effect of this process on the functional properties of the coating, and the integrity of the incorporated active compounds were investigated. Two coatings have been studied, a control fish gelatin-glycerol, and an active one containing gallic acid (GA) as a natural antioxidant. Three powers of the corona process were applied on wet coatings. In the test conditions, there were no improvements in the gelatin crosslinking, but the corona did not cause any structural changes. However, when the corona and gallic acid were combined, the oxygen permeability was significantly reduced, while free radical scavenging, reduction, and chelating properties remained unaffected or slightly improved.

DDPH, a novel antihypertensive agent, is a potential dual inhibitor of hepatic CYP2D and CYP3A.

DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride) is a promising novel antihypertensive agent, with potent antihypertensive, neuroprotective and cardioprotective effects. This study aimed to investigate the effects of DDPH on the expression and activity of hepatic cytochrome P450 (CYP) isoforms and evaluate the metabolic drug-drug interactions of DDPH with propafenone. Our results showed that orally administered DDPH (12.5-50 mg/kg/d) for 7 days significantly inhibited CYP2D1 and CYP3A1 activity and mRNA and protein expression but weakly increased CYP1A2 activity and expression in rats. Enzyme kinetics studies showed that DDPH was a competitive inhibitor of CYP2D1 and mixed inhibitor of CYP3A1 in rat liver microsomes with Ki values of 3.70 ± 0.42 µM and 4.79 ± 1.10 µM respectively. With human liver microsomes, DDPH was a noncompetitive inhibitor of CYP2D6 (Ki = 0.85 ± 0.06 µM) and mixed inhibitor of CYP3A (Ki = 2.15 ± 0.41 µM). Further in vivo study showed that oral administration of DDPH (12.5-50 mg/kg/d) for 7 days in rats significantly increased the area under the plasma concentration-time curve (AUC) of propafenone by 25.4%-63.9%, with a concomitant decrease in the plasma clearance. In conclusion, the results indicated that DDPH inhibited CYP2D and CYP3A activities and down-regulated their protein expression and mRNA transcription. DDPH might cause metabolic drug-drug interactions through modulation of the activity and expression of CYP2D and CYP3A. This information could be important in the prediction of possible drug-drug interactions as well as for the effective therapy and the limitation of toxicity of DDPH in clinical practice.

Comparative Study of Essential Oils Extracted from Egyptian Basil Leaves (Ocimum basilicum L.) Using Hydro-Distillation and Solvent-Free Microwave Extraction.

Solvent-free microwave extraction (SFME) and conventional hydro-distillation (HD) were used for the extraction of essential oils (EOs) from Egyptian sweet basil (Ocimum basilicum L.) leaves. The two resulting EOs were compared with regards to their chemical composition, antioxidant, and antimicrobial activities. The EO analyzed by GC and GC-MS, presented 65 compounds constituting 99.3% and 99.0% of the total oils obtained by SFME and HD, respectively. The main components of both oils were linalool (43.5% SFME; 48.4% HD), followed by methyl chavicol (13.3% SFME; 14.3% HD) and 1,8-cineole (6.8% SFME; 7.3% HD). Their antioxidant activity were studied with the 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical scavenging method. The heating conditions effect was evaluated by the determination of the Total Polar Materials (TPM) content. The antimicrobial activity was investigated against five microorganisms: two Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and one yeast, Candida albicans. Both EOs showed high antimicrobial, but weak antioxidant, activities. The results indicated that the SFME method may be a better alternative for the extraction of EO from O. basilicum since it could be considered as providing a richer source of natural antioxidants, as well as strong antimicrobial agents for food preservation.

Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH.

1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg) significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10(-5) M) also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue.

Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma.

AIM: To evaluate the efficacy of transarterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) in lipiodol (LPD) in the treatment of hepatocellular carcinoma (HCC). METHODS: The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension. The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD. TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected. These patients received additional TACE using the same agent. TACE was repeated until complete regression of the tumor was obtained. The primary efficacy endpoint of the current study was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. RESULTS: The objective early response rate was 43.6%. Cumulative PFS rates were 56.7% at 6 mo, 23.1% at 12 mo, 13.4% at 18 mo, and 10.5% at 24 mo. The median PFS was 6.6 mo. Cumulative survival rates were 90.6% at 6 mo, 81.9% at 12 mo, 70.5% at 24 mo, and 58.8% at 36 mo. Median survival time was 46.6 mo. All adverse reactions were controllable by temporary suspension of treatment. No serious complications or treatment-related deaths were observed. CONCLUSION: TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.

The Time-dependent Manner of Reversible Effect of DDPH on Post-proliferation of PASMC / 医学研究杂志

Objective To study the effect of hypoxial endothelia cell conditional medium(HECCM)on the proliferation of pulmonary arterial muscle cell(PASMC).Methods MTT assay was used to test the proliferation,immuno-cytochemistry was used to identify the expression of ?-SM-actin.Results(1)HECCM could promote the proliferation of PASMC,down-regulate their expression of ?-SM-actin.(2)DDPH could up-regulate the expression of ?-SM-actin in PASMC which was time-dependant.Conclusions DDPH could reverse the phenotype transformation of PASMC exposed to HECCM,the action was time-dependant.After some time DDPH could reversly transform PASMC to the normal contractile phenotype.

Inhibitory effects of levo-phenoprolamine hydrochloride on experimental arrhythmias / 中国药理学通报

AIM To investigate the effects of levo phenoprolamine hydrochloride [ levo 1 (2,6 dimethylphenoxy) 2 (3,4 dimethoxyphenyl ethylamino) propane hydrochloride] [ l DDPH([?]D 25 1 08)]on experimental arrhythmias. on experimental arrhythmias. METHODS Intravenous administration of ouabain, aconitine or CaCl 2 induced arrhythmias in rats or guinea pigs; Microelectrode recording was used to record action potential; Whole cell patch clamp technique was used to record L type calcium current ( I Ca,L ). RESULTS ① l DDPH 50 mg?kg -1 inhibited the ventricular arrhythmias induced by intravenous injection of ouabain in guinea pigs or aconitine and CaCl 2 in rats. ② l DDPH 30 ?mol?L -1 shortened 50% action potential duration (APD 50 ) and prolonged effective refractory period (ERP) ( n =6, P