In vitro study of the effects of plaunotol on oral cell proliferation and wound healing

Plaunotol is an acyclic diterpene alcohol extracted from a medicinal plant called plau-noi, Croton stellatopilosus Ohba, and has been widely used for the treatment of gastric ulcers in Japan. The aim of this study was to examine the effects of plaunotol on human gingival fibroblasts (HGFs) and human oral keratinocytes (HOKs). To assess the cytotoxic effect, HGFs and HOKs were treated with plaunotol. Subsequently, the morphology of cells was recorded and cells were subjected to MTT assay. To investigate cell proliferation effect, cells were treated with plaunotol and counted with a haemocytometer. To determine wound healing effect, the number of cells repopulated into the wounded areas in monolayer culture and in fibroblast-populated collagen lattice (FPCL) was measured. The results showed that 10 and 1?μg/ml (33 and 3.3?μmol/l) plaunotol induced toxicity in HGFs and HOKs, respectively. However, 0.1?μg/ml (0.33?μmol/l) plaunotol promoted HGF proliferation and wound healing in monolayer and FPCL models. In contrast, 0.1?μg/ml plaunotol could not induce HOK proliferation nor in vitro wound healing using monolayer culture, but it induced wound healing in a modified FPCL model. Our data suggested that plaunotol could promote oral cell proliferation and wound healing in vitro and may have an implication on oral wound healing.     

Effect of freeze dried bovine amniotic membrane extract on full thickness wound healing

This study explored the feasibility of development of solubilized amniotic membrane extract (AME) as a potential wound healing substrate with improved efficacy. Bovine amniotic membrane was extracted using a mixture of acetic acid and 2-mercaptopropionic acid under sonication, which was followed by the frozen, and then lyophilized processes. The effects of AME on cell migration and growth properties were evaluated from 0 to 24 h of post injury using primary human foreskin fibroblast monolayer culture with one line scratch as an in vitro wound model. Its wound healing efficacy and scar preventive effects were investigated using whole thickness biopsy punch (8 mm) wound model obtained from rabbit ear. Intra dermal injections of AME fluid (10 μl of 1.2 μg/μl) on four wound sites were performed at 1 h pre injury, post 1, 2 and 3 day. The processes and levels of re-epithelialization and dermal regeneration were examined through histological assessment with H–E staining. In cell migration study conducted at 24 h post injury, AME (1.7 μg/ml) treated cells significantly increased wound closure with 54.9 % compared to control. Histological image analysis on AME treated wound sites at 36 days post injury showed properly developed epidermal basal cell layers and weave-like dermal collagen bundles, whereas those of untreated control skin showed over-proliferation of epidermis and aggregated collagen bundles with defected dermal regeneration. The results of this study verified the feasibility of dermal injections of freeze dried AME as a potential wound healing substrate which can promote epidermal and dermal regeneration, while avoiding undesirable hyper-proliferation of damaged tissue.     

Dracorhodin perchlorate regulates fibroblast proliferation to promote rat's wound healing

In recent years, plant-derived extracts are increasing interest from researchers worldwide due to good efficacy and lower side effects. Among the different plant extracts, Dracorhodin perchlorate (DP) is originated from Dragon's blood which has long been used as a natural medicine with various pharmacological activities. In the present study, we have explored the potential regulation of DP on fibroblast proliferation which promotes wound healing both in vitro and in vivo. DP at treatment of 12–24 h significantly induced fibroblast proliferation which is associated with increasing level of phosphorylated-extracellular signal-regulated kinase (ERK). Moreover, if ERK is halted with siRNA, DP cannot induce fibroblast proliferation. In vivo, DP ointment treatment at low- (2.5 μg/mL), medium- (5 μg/mL) and high-(10 μg/mL) doses, rat wounds healed more rapidly compared with the control group. After DP treatment for 7 days, Serpin family H member 1 (SERPINH1) staining confirmed enhanced fibroblast proliferation in the wound tissue. Finally, phosphorylated-ERK in the wound tissue remarkably increased with DP ointment treatment. Therefore, DP may be developed into a potential lead compounds for the treatment of wounds in clinical trials in the near future.     

The in vitro exposure to cypermethrin does not inhibit the proliferative response of peripheral blood mononuclear cells

This study evaluated the effect of in vitro exposure to cypermethrin on peripheral blood mononuclear cells proliferative response, considering reduced peripheral blood mononuclear cells proliferative response observed in individuals occupationally exposed to pyrethroids. Peripheral blood mononuclear cells were obtained from 21 healthy subjects (28.0?±?9.0 years old). The effect of cypermethrin (at 0.5, 1.0 and 5.0?mg/ml) on cell viability was evaluated by flow cytometry using an apoptosis detection kit. Cell proliferation (PI) was evaluated by 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) fluorescence decay using flow cytometry. Cells labeled with CFSE were exposed, in vitro, to cypermethrin (0.5, 1.0, 2.0, 2.5 and 4?μg/ml) and stimulated with phytohemagglutinin (PHA 1.0 or 5.0?μg/ml) for 5?d (37?°C, 5% CO₂). The in vitro treatment of peripheral blood mononuclear cells with cypermethrin did not induce apoptosis or necrosis after 5?d in culture. Stimulation by PHA induced cell proliferation (PI?=?1.29?±?1.09 and 2.01?±?0.62, PHA at 1.0 and 5.0?μg/ml, respectively, mean?±?SD) and in vitro exposure to cypermethrin did not alter cellular proliferative response to PHA (PI?=?1.80?±?0.50, 2.60?±?0.05 and 2.10?±?1.20 for cypermethrin at 1.0, 2.0 and 4.0?μg/ml, respectively, and PHA at 5.0?μg/ml). In vitro treatment of peripheral blood mononuclear cells with cypermethrin, at the doses tested, does not affect cell viability or proliferation. These findings suggest that the reduction of proliferation observed on lymphocytes derived from individuals occupationally exposed to pesticides may be related to other mechanisms than direct action of cypermethrin on lymphocytes.     

Antimalarial and cytotoxic quassinoids from the roots of Brucea javanica

Two new quassinoids, brujavanol A (1) and brujavanol B (2), along with five known quassinoids (3–7), were isolated from the roots of Brucea javanica. Their structures were elucidated by spectroscopic methods. The antimalarial and cytotoxic activities of the isolated compounds were also assessed. Compounds 1 and 2 exhibited significant in vitro cytotoxicity against human oral cavity cancer (KB) cells with IC₅₀ values of 1.30 and 2.36 μg/ml, respectively, whereas compound 3 showed excellent antiplasmodial activity against the Plasmodium falciparum strains, K1 (IC₅₀ = 0.58 μg/ml).     

New cyclomyrsinol diterpenes from Euphorbia aellenii with their immunomodulatory effects

Chloroform–acetone extract of the aerial parts of Euphorbia aellenii Rech. f. (Euphorbiaceae) was investigated for its diterpenoidal constituents. This led to the isolation of two new and one known cyclomyrsinol-type diterpenes 1–3. The structures were elucidated on the basis of 1D and 2D ¹H and ¹³C NMR techniques, and in vitro immunomodulatory activity was evaluated by standard proliferation of human peripheral blood lymphocytes. Results showed that all the three compounds were found to inhibit lymphocyte proliferation significantly (p < 0.05) at 50 μg/ml concentration. Among them, compound 2 showed more activity against phytohemagglutinin-activated T-cell proliferation with an IC₅₀ of 40.4 ± 9.35 μg/ml.     

Acemannan Stimulates Gingival Fibroblast Proliferation; Expressions of Keratinocyte Growth Factor-1, Vascular Endothelial Growth Factor,and Type I Collagen; and Wound Healing

Aloe vera has long been used as a traditional medicine for inducing wound healing. Gingival fibroblasts (GFs) play an important role in oral wound healing. In this study, we investigated the effects of acemannan, a polysaccharide extracted from Aloe vera gel, on GF proliferation; keratinocyte growth factor-1 (KGF-1), vascular endothelial growth factor (VEGF), and type I collagen production; and oral wound healing in rats. [³H]-Thymidine incorporation assay and ELISA were used. Punch biopsy wounds were created at the hard palate of male Sprague Dawley rats. All treatments (normal saline; 0.1% triamcinolone acetonide; plain 1% Carbopol^®; and Carbopol^® containing 0.5%, 1%, and 2% acemannan (w/w)) were applied daily. Wounded areas and histological features were observed at day 7 after treatment. From our studies, acemannan at concentrations of 2, 4, 8, and 16 mg/ml significantly induced cell proliferation (P<0.05). Acemannan concentrations between 2 – 16 mg/ml significantly stimulated KGF-1, VEGF, and type I collagen expressions (P<0.05). Wound healing of animals receiving Carbopol^® containing 0.5% acemannan (w/w) was significantly better than that of the other groups (P<0.05). These findings suggest that acemannan plays a significant role in the oral wound healing process via the induction of fibroblast proliferation and stimulation of KGF-1, VEGF, and type I collagen expressions.     

Simultaneous determination and pharmacokinetic analysis of seven alkaloids and two flavonoids from rat plasma by HPLC–DAD after oral administration of Wuzhuyu decoction

A simple and sensitive high-performance liquid chromatographic method was developed for the simultaneous determination and pharmacokinetic analysis of seven alkaloids dehydroevodiamine (DHED), 10-hydroxyrutaecarpine (HDR), evodiamine (EDM), rutaecarpine (RCP), 1-methyl-2-n-nonyl-4(1H)quinolone (MNQ), evocarpine (ECP), and dihydroevocarpine (DHE), and two flavonoids isorhamnetin-7-O-rutinoside (RIM) and diosmetin-7-O-β-d-glucopyranoside (GRD) in rat plasma after oral administration of Wuzhuyu decoction. The flow rate was kept at 1.0 ml/min and the detection wavelength was set at 300 nm. The calibration curves were linear in the range of 0.5013–30.076 μg/ml for DHED, 0.2161–21.608 μg/ml for RIM, 0.161–12.876 μg/ml for HDR, 0.2146–21.457 μg/ml for GRD, 2.0464–40.928 μg/ml for EDM, 1.0398–31.194 μg/ml for RCP, 0.5970–35.818 μg/ml for MNQ, 0.8371–20.928 μg/ml for ECP, and 0.5167–31.003 μg/ml for DHE. The precision (relative standard deviation (RSD), %) for all was less than 10% and the accuracy (relative error (RE), %) was within ± 10%. The results demonstrated that the assay had remarkable reproducibility with acceptable accuracy and precision. The lower limit of quantifications for the compounds in plasma ranged from 0.12 to 0.23 μg/ml and the lower limit of detections ranged from 0.024 to 0.076 μg/ml. This validated method has been successfully applied in the pharmacokinetics study of seven alkaloids and two flavonoids after orally administrating the Wuzhuyu decoction to rats.     

Structure characterization and immunocompetence of a glucan from the fruiting bodies of Cantharellus cibarius

A protein-bound polysaccharide fraction (JBP-1) was obtained from the fruiting bodies of Cantharellus cibarius. Its chemical composition was studied by the cooperative usage of multiple chemical and spectral methods and characterized to be a fraction with a molecular weight of 4.8 × 10⁵ Da and only composed of glucose. Methylation analysis revealed that the sugar residues in JBP-1 are existing as t-, 1,6-, and 1,3,6-linked Glcp sugar residues. The immunocompetence of the fraction was evaluated with the proliferation assay of mouse splenocytes, and the result revealed that JBP-1 could significantly stimulate the proliferation of mouse splenocytes in a dose-dependent manner, with p < 0.001 at the concentration of 100 μg/ml and 30 μg/ml, p < 0.05 at 10 μg/ml. These results give us a primary scientific evidence to further explore the pharmaceutical function of this mushroom.     

Effects of Cadmium on Bovine Corneal Endothelial Cells In Vitro

Abstract

Cadmium at a concentration of 0.5 µg/ml has been shown to be toxic to bovine corneal endothelial cells in vitro. The toxicity could be observed within 24 hr and exhibited a dose-response relationship. After exposure to 0.1 µg/ml cadmium for 24 hr, the cells were morphologically normal. Prolonged treatment, however, caused a decrease in the density of nuclei at 168 hr. At higher dosages (0.5 and 1.0 µg/ml cadmium), a similar decrease in the density of nuclei was observed at 48 hr. The effect was aggravated by extending the exposure time to 168 hr. We propose that cadmium may interfere with the energy metabolism in bovine corneal endothelial cells in vitro, leading to the disruption of the monolayer structure and cell shape.     

Antioxidant capacity of Typha angustifolia extracts and two active flavonoids

Context: The pollen of Typha angustifolia L. (Typhaceae) has been used as a traditional Chinese medicine for improving the microcirculation and promoting wound healing. Flavonoids are the main constituent in the plant, but little is known about the antioxidant activity of the principal constituent of the pollen in detail.

Objectives: To assess the antioxidant activities of ethanol and water extracts and two constituents of the pollen.

Materials and methods: Plant material (1?g) was extracted by 95% ethanol and water (10?mL?×?2, 1?h each), respectively. The extracted activities (0.8–2.6?mg/mL) were measured by DPPH and the reducing activity of ferric chloride (1.7–2.6?mg/mL). Typhaneoside and isorhamnetin-3-O-neohesperidoside (I3ON) (2.8–70?μmol/L) were investigated on the relationship between NO, MDA and SOD in HUVECs treated with 100?μg/mL of LPS for 24?h.

Results: Nine compounds were identified by UPLC-MS. Ethanol extract showed IC₅₀ values in DPPH (39.51?±?0.72) and Fe³⁺ reducing activity (82.76?±?13.38), higher than the water extract (50.85?±?0.74) and (106.33?±?6.35), respectively. Typhaneoside and I3ON promoted cell proliferation at the respective concentration range of 2.8 to 70?μmol/L (p?p?p?p?Conclusions: The constituents from Typha angustifolia could be a novel therapeutic strategy for LPS-induced inflammation.     

In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing

Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity. Phenytoin-loaded alkyd nanoemulsions generally resulted in higher mean cell viability compared with equivalent concentration of phenytoin solutions, suggesting that the nanoemulsions provided a controlled-release property that maintained the optimum phenytoin level for keratinocyte growth. HaCaT cell proliferation, measured by 5-bromo-2-deoxyuridine uptake, was found to increase following exposure to increasing phenytoin concentration from 25 to 50 μg/mL in solution or encapsulated in nanoemulsions but declined at a drug concentration of 100 μg/mL. An in vitro cell monolayer wound scratch assay revealed that phenytoin solution or nanoemulsions producing 50 μg/mL phenytoin concentration resulted in 75%-82% “scratch closure” after 36 h, similar to medium containing 10% fetal bovine serum as a cell growth promoter. These findings indicate that phenytoin-loaded alkyd nanoemulsions show potential for promoting topical wound healing through enhanced proliferation of epidermal cells.     

Pro-apoptotic and microtubule-disassembly effects of ardisiacrispin (A+B), triterpenoid saponins from Ardisia crenata on human hepatoma Bel-7402 cells

Ardisiacrispin (A+B) is a mixture of ardisiacrispins A and B, derived from Ardisia crenata with a fixed proportion (2:1). The present study was conducted to investigate its anticancer activity on human cancer cells and its underlying mechanism of action. The (IC₅₀)s of ardisiacrispin (A+B) on proliferation of several human cancer cell lines were in the range of 0.9–6.5 μg/ml by sulphorhodamine B-based colorimetric assay, in which Bel-7402 was the most sensitive cell line. Moreover, ardisiacrispin (A+B) induced dose-dependent apoptosis in Bel-7402 cells at doses of 1–10 μg/ml by flow cytometry, and resulted in the changes of the mitochondrial membrane depolarization, membrane permeability enhancement, and nuclear condensation in a dose-dependent manner through high-content screening analysis. Furthermore, ardisiacrispin (A+B) could disassemble microtubule in Bel-7402 cells; the fluorescence intensity of microtubules decreased at the concentration of 5–20 μg/ml. These findings suggest that ardisiacrispin (A+B) could inhibit the proliferation of Bel-7402 cells by inducing apoptosis and disassembling microtubule.     

Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine

The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box–Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (J_ss) of SIN from PLO was 146.55?±?2.93?μg/cm²/h, significantly higher than that of gel (120.39?μg/cm²/h) and the amount of SIN deposited in skin from the PLO was 10.08?±?0.86?μg/cm², significantly larger than that from gel (6.01?±?0.04?μg/cm²). In vivo skin microdialysis studies showed that the maximum concentration (C_max) of SIN from PLO in “permeation study” and “drug-deposition study” were 150.27?±?20.85?μg/ml and 67.95?μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73?μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.     

Chemical constituents from the roots of Feroniella lucida

A new furanocoumarin named lucidafuranocoumarin A (7) together with 13 known coumarins (1–6, 8–14) and four known alkaloids (15–18) was isolated from the roots of Feroniella lucida. Their structures were elucidated on the basis of spectroscopic analysis. Some of the isolates were evaluated for their biological activities, and compound 18 showed strong cytotoxicity against KB (IC₅₀ = 0.637 μg/ml) and NCI-H187 (IC₅₀ = 0.094 μg/ml) human cancer cell lines, antimalarial activity against Plasmodium falciparum (IC₅₀ = 0.336 μg/ml), and antituberculosis activity against Mycobacterium tuberculosis (MIC = 6.25 μg/ml).     

Antiviral activity of Rheum palmatum methanol extract and chrysophanol against Japanese encephalitis virus

Rheum palmatum, Chinese traditional herb, exhibits a great variety of anti-cancer and anti-viruses properties. This study rates antiviral activity of R. palmatum extracts and its components against Japanese encephalitis virus (JEV) in vitro. Methanol extract of R. palmatum contained higher levels of aloe emodin, chrysophanol, rhein, emodin and physcion than water extract. Methanol extract (IC₅₀ = 15.04 μg/ml) exhibited more potent inhibitory effects on JEV plaque reduction than water extract (IC₅₀ = 51.41 μg/ml). Meanwhile, IC₅₀ values determined by plaque reduction assay were 15.82 μg/ml for chrysophanol and 17.39 μg/ml for aloe-emodin, respectively. Virucidal activity of agents correlated with anti-JEV activity, while virucidal IC₅₀ values were 7.58 μg/ml for methanol extract, 17.36 μg/ml for water extract, 0.75 μg/ml for chrysophanol and 0.46 μg/ml for aloe-emodin, respectively. In addition, 10 μg/ml of extract, chrysophanol or aloe emodin caused 90 % inhibition of JEV yields in cells and significantly activated gamma activated sequence-driven promoters. Hence, methanol extract of R. palmatum and chrysophanol with high therapeutic index might be useful for development of antiviral agents against JEV.     

Biotransformation of nodakenin and simultaneous quantification of nodakenin and its aglycone in incubated system of human intestinal bacteria by HPLC method

When nodakenin (1) was anaerobically incubated with human intestinal bacteria, nodakenetin (2) was found as a main biotransformed product. We developed a simple and selective reversed-phase high-performance liquid chromatographic method for simultaneous quantification of 1 and 2 in incubated system of human intestinal bacteria with 1. Chromatographic separation of 1 and 2 was performed on an analytical C₁₈ column, with a mobile phase of MeOH–H₂O (4:6, v/v) at a flow rate of 1.0 ml/min and the UV detection was at 330 nm. The calibration curves were linear over the range of 0.15–24.0 μg/ml for 1 and 0.7–13.2 μg/ml for 2. The lower limits of detection and quantification were 0.01 and 0.1 μg/ml for 1, and 0.005 and 0.05 μg/ml for 2. The recoveries were (87.66 ± 1.66), (79.89 ± 2.53), and (82.96 ± 5.61)% at 1.0, 2.0, and 8.0 μg/ml, respectively, for 1 and (88.32 ± 4.12), (78.15 ± 4.39), and (76.22 ± 3.29)% at 1.0, 4.0, and 16.0 μg/ml, respectively, for 2. The intra- and interday precision and accuracy were validated by relative standard deviation, which were in the ranges of 1.25–4.16 and 2.16–6.12% for 1, and 1.98–6.45 and 2.56–4.57% for 2, respectively. This method has been applied to the simultaneous quantitation of 1 and 2 in incubated system of human intestinal bacteria with 1.     

In vivo and in vitro toxicological evaluations of aqueous extract from Cecropia pachystachya leaves

ABSTRACT

Cecropia pachystachya

leaves are popularly used to treat asthma and diabetes. Despite the widespread consumption of this plant, there are few scientific studies regarding its toxicological potential. In order to conduct a thorough study concerning the potential adverse effects, the aim of this study was to assess acute and subacute toxicity tests of crude aqueous extract from C. pachystachya leaves (CAE-Cp) using in vivomodel, as well as in vitro cytotoxicity, genotoxicity and antioxidant activity. In addition, genotoxicity, and cytotoxicity of chlorogenic acid (CGA) and cytotoxicity of isoorientin (ISOO) were also evaluated. The antioxidant activity was verified by DPPH, cytotoxicity using sulforhodamine B (SRB) assay and genotoxicity by comet assay on V79 cells. The phytochemical analysis of CAE-Cp detected flavonoids and tannins, CGA and ISOO as the major compounds utilizing HPLC. The total flavonoid content (6.52 mg/g EQ) and antioxidant activity (EC₅₀ = 62.15 µg/ml) of CAE-Cp were determined. In vitro evaluations with CAE-Cp showed genotoxic effects at 0.31 to 2.5 mg/ml and an expressive cytotoxicity on HT-29 (IC₅₀ = 4.43 µg/ml) cells. CGA was genotoxic against V79 cells at 0.07 mg/ml and cytotoxic against to HT-29 (IC₅₀ = 71.70 µg/ml), OVCAR-3 (IC₅₀ = 80.07 µg/ml), MCF-7 (IC₅₀ = 45.58 µg/ml) and, NCI-H460 (IC₅₀ = 71.89 µg/ml) cancer cell lines. Wistar rats treated with a single dose (2,000 mg/kg) CAE-Cp decreased hemoglobin levels after 14 days, although no significant toxicity was observed in animals after 28 days. In view of the in vitro cytotoxicity and genotoxicity detected, further studies are necessary to establish the safe use of CAE-Cp.     

Improved oral absorption and anti-lung cancer activity of paclitaxel-loaded mixed micelles

The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5?±?1.8?nm with a polydispersity index of 0.265?±?0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09?±?0.09% and 95.67?±?2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78?±?0.14?mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC₅₀ values of PTX-TP-M (3.14?±?0.85 and 8.28?±?1.02?μg/mL) were lower than those of PTX solution (5.21?±?0.93 and 14.53?±?1.96?μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.     

吡喹酮对体外培养的日本血吸虫的作用

吡喹酮(Praziquantel,Embay 8440)系一种具有抗绦虫和抗血吸虫作用的广谱抗寄生虫新药。动物实验证明,该药对小鼠、家兔和犬的日本血吸虫病都有很好的疗效,且毒性低,疗程短;临床上用吡喹酮的1～2天疗法治疗日本血吸虫病,总剂量为45～90mg/kg时,治后半年的粪检虫卵转阴率达99.7％。本文报道吡喹酮对体外培养的日本血吸虫的作用。