Beverage-induced enhanced bioavailability of carbamazepine and its consequent effect on antiepileptic activity and toxicity

The present study was undertaken to investigate the food–drug interaction of carbamazepine (CBZ). Common fruit juices [grapefruit juice (GFJ), lime juice (LJ)], known to inhibit the enzyme cytochrome P450 3A4 (CYP3A4), and some widely consumed beverages [milk (M), black tea (BT)] were involved in this study in the presence of CBZ, as might happen during clinical therapy. The effects of the beverages on the pharmacokinetics and drug-induced toxicity of CBZ was observed after concomitant administration for a period of 28 days. Accordingly, the influence of altered bioavailability of CBZ on its antiepileptic activity was investigated. A significant shift in the C_max as well as T_max of CBZ was observed in the presence of LJ and GFJ. This increase in bioavailability significantly enhanced hepatotoxicity and delayed the onset of tremor and piloerection against pentylene tetrazole (PTZ)-induced seizure in experimental animals. However, increased toxicity of CBZ was found to be absent with BT. Thus, from our observation, LJ or GFJ in the presence of CBZ significantly increased the bioavailability of CBZ, which might lead to increased toxicity and antiepileptic activity of the drug.     

Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up

The relation between consumption of coffee, tea and caffeine and risk of breast cancer remains unsettled. We examined data from a large, long-term cohort study to evaluate whether high intake of coffee and caffeine is associated with increased risk of breast cancer. This was a prospective cohort study with 85,987 female participants in the Nurses' Health Study. Consumption of coffee, tea and caffeine consumption was assessed in 1980, 1984, 1986, 1990, 1994, 1998 and the follow-up continued through 2002. We documented 5,272 cases of invasive breast cancer during 1,715,230 person-years. The multivariate relative risks (RRs) of breast cancer across categories of caffeinated coffee consumption were: 1.0 for <1 cup/month (reference category), 1.01 (95% confidence interval: 0.92-1.12) for 1 month to 4.9 week, 0.92 (0.84-1.01) for 5 week to 1.9 days, 0.93 (0.85-1.02) for 2-3.9 days, 0.92 (0.82-1.03) for >or=4 cups per day (p for trend = 0.14). Intakes of tea and decaffeinated coffee were also not significantly associated with risk of breast cancer. RRs (95% CI) for increasing quintiles of caffeine intake were 1.00, 0.98 (0.90-1.07), 0.92 (0.84-1.00), 0.94 (0.87-1.03) and 0.93 (0.85-1.01) (p for trend = 0.06). A significant inverse association of caffeine intake with breast cancers was observed among postmenopausal women; for the highest quintile of intake compared to the lowest RR 0.88 (95% CI = 0.79-0.97, p for trend = 0.03). We observed no substantial association between caffeinated and decaffeinated coffee and tea consumption and risk of breast cancer in the overall cohort. However, our results suggested a weak inverse association between caffeine-containing beverages and risk of postmenopausal breast cancer.     

绿茶对交链孢霉代谢物致突变性的抑制作用

观察绿茶对交链孢酚单甲醚(AME)和B_(2-a6)提取物诱导人胚肺2BS细胞SCE的影响。结果表明:不同浓度的绿茶,均不能增加SCE的频率,但在绿茶存在的情况下,由AME(10μg/ml)和B_(2-a6)(0.1mg/ml)所诱导的SCE频率比没有绿茶时低(P<0.01),并呈剂量—效应关系。结果提示:绿茶对某些霉菌毒素的致突变性有抑制作用。     

Bioactive nutrients - Time for tolerable upper intake levels to address safety

There is increasing interest by consumers, researchers, and regulators into the roles that certain bioactive compounds, derived from plants and other natural sources, can play in health maintenance and promotion, and even prolonging a productive quality of life. Research has rapidly emerged suggesting that a wide range of compounds and mixtures in and from plants (such as fruits and vegetables, tea and cocoa) and animals (such as fish and probiotics) may exert substantial health benefits. There is interest in exploring the possibility of establishing recommended intakes or dietary guidance for certain bioactive substances to help educate consumers. A key aspect of establishing dietary guidance is the assessment of safety/toxicity of these substances. Toxicologists need to be involved in both the development of the safety framework and in the evaluation of the science to establish maximum intake/upper limits.     

Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage

The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of both compounds, along with imparting antioxidant and anti-aging effects. Transfersomes were prepared by thin film hydration technique, using soy phosphatidylcholine and sodium cholate, combined with high-pressure homogenization. They were characterized with respect to size, polydispersity index, zeta potential, morphology, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro antioxidant activity and ex vivo skin permeation studies. Cell viability, lipid peroxidation, intracellular ROS levels and expression of MMPs (2 and 9) were determined in human keratinocyte cell lines (HaCaT). The composition of the transfersomes was statistically optimized by Design of Experiments using Box–Behnken design with four factors at three levels. The optimized transfersome formulation showed vesicle size, polydispersity index and zeta potential of 101.2?±?6.0?nm, 0.245?±?0.069 and ?44.8?±?5.24?mV, respectively. FTIR and DSC showed no interaction between EGCG and the selected excipients. XRD results revealed no form conversion of EGCG in its transfersomal form. The optimized transfersomes were found to increase the cell viability and reduce the lipid peroxidation, intracellular ROS and expression of MMPs in HaCaT cells. The optimized transfersomal formulation of EGCG and HA exhibited considerably higher skin permeation and deposition of EGCG than that observed with plain EGCG. The results underline the potential application of the developed transfersomes in sunscreen cream/lotions for improvement of UV radiation-protection along with deriving antioxidant and anti-aging effects.     

In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates

Context: Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance.

Objectives: The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated.

Materials and methods: TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis.

Results: The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0?μg/mL) and WIF and FLZ (1.95:8.0?μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700–800?cm^?1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF.

Conclusions: DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat’s claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.     

Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the issues of bioavailability, drug design, and nano-formulation, in order to achieve successful clinical outcomes with promising activity and tolerability.     

Tea polyphenols alleviate tri‐ortho‐cresyl phosphate‐induced autophagy of mouse ovarian granulosa cells

Tri‐ortho‐cresyl phosphate (TOCP), a widely used plasticizer in industry, can cause female reproductive damage. Tea polyphenols (TPs) have multiple health effects via inhibiting oxidative stress. However, the reproductive protection of TPs in TOCP‐induced female reproductive system damage is yet to be elucidated. In the study, TOCP inhibited cell viability and induced autophagy of mouse ovarian granulosa cells; while TPs could rescue the inhibition of viability and induction of autophagy. 3‐MA, an autophagy inhibitor, could also rescue the inhibition of cell viability. These results indicated that TPs played a protective role in TOCP‐induced autophagy. Furthermore, TPs could inhibit the induction of oxidative stress of the cells by TOCP, which implying that TPs might alleviate TOCP‐induced autophagy via inhibiting oxidative stress. Furthermore, TPs could rescue TOCP‐induced autophagy and oxidative stress in the mouse ovarian tissues. Taken together, these results indicated that TPs could protect TOCP‐induced ovarian damage via inhibiting oxidative stress.     

Effect of theo-polyphenols on hepatic histology of hyperlipidemia model in quails

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余苣降酸茶的HPLC指纹图谱研究

目的:建立余苣降酸茶HPLC指纹图谱,以控制该中药复方茶剂的质量。方法:采用HPLC梯度洗脱法测定余苣降酸茶的指纹图谱,色谱柱为Waters Sun Fire C18色谱柱(250 mm×4.6 mm,5μm);流动相为0.2%磷酸水溶液-乙腈,柱温:30℃,检测波长:308 nm,进样量:10μl,流速:1.0 ml·min^-1。结果:测得10批余苣降酸茶供试品HPLC色谱图,并标示出20个共有峰,确定其中2个已知峰分别为没食子酸和葛根素;并明确了20个共有峰的原药材归属。结论:该方法建立的余苣降酸茶HPLC指纹图谱重复性好,色谱峰信息量大,为全面控制该制剂的质量提供了可靠的方法。