Effects of dietary fruits,vegetables and a herbal tea on the in vitro transport of cimetidine: Comparing the Caco-2 model with porcine jejunum tissue

Context: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes.

Objective: To compare the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models.

Materials and Methods: Bi-directional transport of cimetidine was measured across Caco-2 cell monolayers and excised porcine jejunum tissue in the absence (control) as well as the presence of verapamil (positive control) and selected plant extracts.

Results: Sclerocarya birrea Hochst. (Anacardiaceae) (marula) and Psidium guajava L. (Myrtaceae) (guava) crude extracts significantly decreased cimetidine efflux in both in vitro models resulting in increased absorptive transport of the drug. On the other hand, Dovyalis caffra Sim. (Flacourtiaceae) (Kei-apple), Prunus persica (L.) Batsch (Rosaceae) (peach), Aspalathus linearis (Burm. f.) R. Dahlgren (Fabaceae) (rooibos tea), Daucus carota L. (Apiaceae) (carrot), Prunus domestica A. Sav. (Rosaceae) (plum), Beta vulgaris L. (Chenopodiaceae) (beetroot) and Fragaria x ananassa (Weston) Duchesne ex Rozier. (Rosaceae) (strawberry) crude extracts exhibited different effects on cimetidine transport between the two models.

Discussion: Caco-2 cells were more sensitive to changes in cimetidine transport by the plant extracts and therefore may overestimate the effects of co-administered plant extracts on drug transport compared to the excised pig tissue model, which is congruent with findings from previous studies.

Conclusions: The excised porcine jejunum model seemed to provide a more realistic estimation of botanical-drug pharmacokinetic interactions than the Caco-2 cell model.     

变黑白头翁提取物降低亚砷酸盐对小鼠精细胞的毒性

目的：研究变黑白头翁提取物降低亚砷酸盐对小鼠精细胞毒性的作用。方法：给予实验小鼠亚砷酸钠（20mg／kg每日），并分别在第30、60、90天对小鼠进行检测。亚砷酸盐中毒小鼠被分为2组，其中一组给予变黑白头翁提取物（35mg／kg），另一组给予85％乙醇。通过检测小鼠精细胞凋亡标志蛋白CYP1A1、p53及caspase3的活性，确定细胞及DNA的损伤情况，并测定睾丸毒性标志物的水平。通过圆二色光谱仪及熔化温度数据检测变黑白头翁提取物与DNA的相互作用情况。结果：亚砷酸盐中毒小鼠的所有细胞凋亡标志蛋白及睾丸毒性标志物的水平均有所上升，而经变黑白头翁提取物治疗的小鼠上述各项指标均降低或恢复至正常水平。变黑白头翁提取物与DNA相互作用，引起了DNA结构和构象的变化。结论：变黑白头翁提取物可作为砷中毒引起的生殖功能损害的治疗药物给予研究和开发。     

Seasonal Variation of Phyto-Constituents of Tea Leaves Affects Antiproliferative Potential

Objective: Tea (Camellia sinensis Linn.; family: Theaceae) is popular as a stimulant beverage across the globe and is also utilized as a functional antioxidant in alternative medicine. This study has evaluated the impact of seasonal variation on phyto-constituents of tea.

Method: The antiproliferative potential of methanolic extracts of tea leaves collected in the rainy season (MECR) was compared with the extract of tea leaves collected in the autumn season (MECA) of the same mother plant. Evaluation of in vivo antitumor activity was carried out in adult female Swiss albino mice groups inoculated with Ehrlich ascites carcinoma (EAC) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to compare efficacy of MECR with that of MECA in the EAC cell line. Both qualitative and quantitative tests for phytochemical constituents present in MECA and MECR were performed. Antitumor efficacy of both the extracts was determined by evaluating different tumor markers showing dose-dependent cytotoxicity.

Results: Statistically significant reduction in EAC-induced tumor was observed in MECR treated mice compared to MECA treated ones. Cell decimation was significantly higher with MECR treatment, where restoration of different parameters including tissue structures returned to normal. Moreover, gas chromatography–mass spectrometry (GC-MS) study revealed the presence of cyclobarbital and benzazulene derivative in MECR, which is thought to be a novel source of these chemicals.

Conclusions: To our knowledge, there is no report that has attempted to reveal nutritional changes in terms of efficacy and variation in anticancer constituents in tea leaves, plucked in two seasons. This study revealed a novel source of barbital and benzazulene derivative. The unique presence of cyclobarbital and benzazulene, as revealed from GC-MS data, in methanolic extract of tea leaves collected during the rainy season (MECR) may have contributed to its enhanced in vitro (adopting MTT assay) and in vivo (on EAC-infected Swiss albino mice) cytotoxicity vis-à-vis antiproliferative properties compared to methanolic extract of tea leaves collected during the autumn season (MECA). The nature of plucking leaves in the two selected seasons is different.     

Plant thorn synovitis of elbow in children

Four rare cases of plant thorn synovitis of left elbow were admitted at our institution, which were initially misdiagnosed as partially treated septic arthritis of elbow or Juvenile inflammatory arthritis. All of them were of paediatric age group. Symptoms included pain, swelling, and decreased range of motion of affected joint. On examination synovitis was present in all patients.Roentgenograms & Ultrasonography were inconclusive in all patients, Definitive diagnosis was made only after arthrotomy, Thorn fragments (Acacia arabica) were recovered from the hypertrophied synovium & subtotal synovectomy was done and sent for histopathological examination. All patients improved after surgery with mean residual flexion deformity of 12.5 ± 2.86°. Plant thorn induced synovitis of elbow is rare, it must be included in the differential diagnosis of monoarthritis of elbow and a high index of suspicion is needed for retained thorn fragments in elbow joint causing synovitis. Its optimal treatment is arthrotomy, foreign body removal and total/subtotal synovectomy.     

Ethnobotanical inventory and medicinal uses of some important woody plant species of Kotli,Azad Kashmir,Pakistan

To document ethnobotanical informations of useful woody plant species in the region of Kotli, Azad Kashmir.MethodsAn ethnobotanical survey was conducted in Kotli. Data were collected by interview and semi structured questionnaire from selected local informants and traditional practitioners as well as by field assessment.ResultsThe present study documented the etnobotanical uses of 33 woody plant species. Most of the species have been used for dual purpose. Only 5 species are used for one purpose. Study revealed all species have medicinal value, among which 21 were used as fuel wood species, 16 as fodder species, 4 as timber wood species, 12 as edible fruit species, 6 as fence or hedge plant, 7 as ornamental species and 12 species had other uses.ConclusionsMedicinal plants are still widely used for health care by locals of Kotli. Some species of woodlands seem to be vulnerable to overcollection and deforestation. As the young generation is diverted toward allelopathic medicines, ethnobotanical knowledges of important medicinal plants are restricted to the old people only. It is suggested to close the forest of district Kotli for next two to three decades for the conservation of plant biodiversity.     

EVALUATION OF ANTIMICROBIAL AND CYTOTOXIC ACTIVITIES OF PLANT EXTRACTS FROM SOUTHERN MINAS GERAIS CERRADO

The antimicrobial activity of plant hidroethanolic extracts on bacteria Gram positive, Gram negative, yeasts, Mycobacterium tuberculosis H37 and Mycobacterium bovis was evaluated by using the technique of Agar diffusion and microdilution in broth. Among the extracts evaluated by Agar diffusion, the extract of Bidens pilosa leaf presented the most expressive average of haloes of growth inhibition to the microorganisms, followed by the extract of B. pilosa flower, of Eugenia pyriformis'' leaf and seed, of Plinia cauliflora leaf which statistically presented the same average of haloes inhibitory formation on bacteria Gram positive, Gram negative and yeasts. The extracts of Heliconia rostrata did not present activity. Mycobacterium tuberculosis H37 and Mycobacterium bovis (BCG) appeared resistant to all the extracts. The susceptibility profile of Candida albicans and Saccharomyces cerevisiae fungi were compared to one another and to the Gram positive Bacillus subtilis, Enterococcus faecalis and the Gram negative Salmonella typhimurium bacteria (p > 0.05). The evaluation of cytotoxicity was carried out on C6-36 larvae cells of the Aedes albopictus mosquito. The extracts of stem and flower of Heliconia rostrata, leaf and stem of Plinia cauliflora, seed of Anonna crassiflora and stem, flower and root of B. pilosa did not present toxicity in the analyzed concentrations. The highest rates of selectivity appeared in the extracts of stem of A. crassiflora and flower of B. pilosa to Staphylococcus aureus, presenting potential for future studies about a new drug development.     

Assessment of the intrinsic radiosensitivity of glioma cells and monitoring of metabolite ratio changes after irradiation by 14.7‐T high‐resolution 1H MRS

Gliomas are the most common type of primary brain tumor. Radiation therapy (RT) is the primary adjuvant treatment to eliminate residual tumor tissue after surgery. However, the current RT guided by conventional imaging is unsatisfactory. A fundamental question is whether it is possible to further enhance the effectiveness and efficiency of RT based on individual radiosensitivity. In this research, to probe the correlation between radiosensitivity and the metabolite characteristics of glioma cells in vitro, a perchloric acid (PCA) extracting method was used to obtain water‐soluble metabolites [such as N‐acetylaspartate (NAA), choline (Cho), creatine (Cr) and succinate (Suc)]. Spectral patterns from these processed water‐soluble metabolite samples were acquired by in vitro 14.7‐T high‐resolution ¹H MRS. Survival fraction analysis was performed to test the intrinsic radiosensitivity of glioma cell lines. Good ¹H MRS of PCA extracts from glioma cells was obtained. The radiosensitivity of glioma cells correlated positively with the Cho/Cr and Cho/NAA ratios, but negatively with the Suc/Cr ratio. Irradiation of the C6 cell line at different X‐ray dosages led to changes in metabolite ratios and apoptotic rates. A plateau phase of metabolite ratio change and a decrease in apoptotic rate were found in the C6 cell line. We conclude that in vitro high‐resolution ¹H MRS possesses the sensitivity required to detect subtle biochemical changes at the cellular level. ¹H MRS may aid in the assessment of the individual radiosensitivity of brain tumors, which is pivotal in the identification of the biological target volume. Copyright © 2014 John Wiley & Sons, Ltd.     

基于UHPLC-MS/MS的药用植物内源性激素含量检测方法及黄花蒿不同器官激素的测定

目的 激素是调控植物活性次生代谢产物合成途径的核心调控因子，内源激素结构多样、含量极低，检测难度高，缺乏高效、准确的检测方法。本研究利用超高效液相色谱串联质谱（UHPLC-MS/MS）技术构建了对黄花蒿中茉莉酸、细胞分裂素、赤霉素、生长素、脱落酸等多类植物内源性激素高效定量检测方法。方法 使用Agilent Poroshell 120 EC-C18（2.7 μm， 3.0×150 mm）色谱柱，流动相为0.05%甲酸水-乙腈溶液，梯度洗脱，采用多反应监测模式验证方法可行性，并对黄花蒿不同器官中植物激素进行定量分析。结果 本方法中检测的16种植物激素均呈良好线性，加样回收率、精密度和稳定性均符合植物样品的测定要求。利用此方法测定青蒿不同器官的激素含量，结果表明脱落酸、茉莉酸、茉莉酸甲酯均在叶中含量较高，赤霉素和生长素在根部含量高，细胞分裂素在叶和茎中含量高。结论 青蒿不同器官的激素测定结果可进一步印证脱落酸、茉莉酸、茉莉酸甲酯在调控青蒿素合成中起着重要作用的相关报道，同时表明该方法检测性良好。本文构建的植物内源性激素的检测方法为进一步探究植物生长发育、抵御外界胁迫的相关机制及次生代谢产物的合成等方面提供了手段。