Effects of nutraceuticals on sprouting of cultured human umbilical vein endothelial cells and growth of sub-intestinal vessels in zebra fish embryos

OBJECTIVE: Nutraceuticals such as resveratrol, catechins, and curcumin have been reported to interfere, among others, with angiogenesis. Based on these reports, we evaluated a number of Surinamese nutraceuticals for their effects on angiogenesis in a cell culture and zebra fish model. DESIGN AND METHODS: Parts from Cecropia peltata, Luffa acutangula, Momordica charantia, Morinda citrifolia, Oenocarpus bacaba, Psidium guajava, and Spondias mombin were extracted with distilled water, freeze-dried, and evaluated for their cytotoxicity in cultured human umbilical vein endothelial cells (HUVEC) using a sulforhodamine B assay, as well as the sprouting of these cells in a scratch-wound assay. In parallel, the plant extracts were assessed for their effects on sub-intestinal vessel length in embryos of the zebra fish Danio rerio. RESULTS: At lowly cytotoxic concentrations (< IC50 values), the C. peltata, L. acutangula, M. charantia, and M. citrifolia extracts yielded 20 to 100% larger wound gap areas when compared to those in untreated cell cultures, while the O. bacaba extract produced a roughly 20% smaller wound gap area. Furthermore, the L. acutangula, M. charantia, and P. guajava extracts inhibited sub-intestinal vessel growth in zebra fish embryos by 30 to 50%, while the O. bacaba preparation stimulated this phenomenon by about 50%. CONCLUSIONS: The inhibitory effects of the L. acutangula, M. charantia, and P. guajava extracts, and the stimulatory effect of the O. bacaba sample on HUVEC sprouting and zebra fish sub-intestinal vessel growth, suggest that these nutraceuticals are able to interfere with angiogenesis.

Evaluation of Surinamese medicinal plants for their effects on the contractility of hypoxic guinea pig myocardial tissue

OBJECTIVE: Cardiac stunning occurs after a transient hypoxic or ischemic insult. Preparations from Anona muricata L., Bixa orelana L., Cecropia palmata Willd., Erythrina fusca Lour., Hibiscus esculentus L., Psidium guajava L., and Terminalia catappa L. were evaluated for their possible positive-inotropic effects in a laboratory model of cardiac stunning. DESIGN AND METHOD: Thus, isolated guinea pig atria perfused in oxygenated Ringer-Locke buffer, were exposed to 5-min periods of hypoxic stress and then allowed to recover for 2 x 3 min in oxygenated buffer alone or supplemented with norepinephrine (10-5 M) or a plant extract (0.001 – 1 mg/mL). Atrial contraction force (F) was measured with a force transducer and contractility was derived by calculation of dF/dt. Troponin C - a highly specific marker for heart muscle cell death - was measured in the perfusion solution in the absence or presence of the plant extracts. RESULTS: Reoxygenation led to a gradual recovery of the atria, but they remained in a state of depressed contractility for at least 4 min. However, exposure to the A. muricata, B. orellana, C. palmata, and T. catappa extracts increased the contractility by 50 to 250%. Notably, troponin C release was 3- to 6-fold higher in incubations with the two latter preparations. CONCLUSION: Preparations from A. muricata, B. orellana, C. palmata, and T. catappa may possess positive-inotropic properties that may be useful in cardiac stunning. However, those from C. palmata and T. catappa may cause myocardial damage that may limit their usefulness in this condition.

Cytotoxic and genotoxic effects of commonly used surinamese medicinal plants in cultured Chinese hamster ovary cells

OBJECTIVE: Medicinal plants are popularly used in Suriname for treating a wide variety of conditions. However, there are often no records about their possible adverse maternal and perinatal effects. For this reason, we assessed a number of commonly used plant-derived folk medicines for their potential genotoxic effects in a cell culture model. DESIGN AND METHODS: Parts from Aloe vera, Apium graveolens, Azaradichta indica, Carica papaya, Cocos nucifera, Dioscorea villosa, Eryngium foetidum, Gossypium barbadense, Momordica charantia, Musa x paradisiaca, and Senna reticulata were extracted with distilled water, freeze-dried, and stored at -20oC. Next, they were evaluated at serial dilutions for their effects on the proliferation of, and DNA damage formation in cultured Chinese hamster ovary (CHO) cells using a sulforhodamine B and a single cell gel electrophoresis (comet) assay, respectively. The latter studies were validated by assessing the DNA strand-breakage induced by etoposide. RESULTS: The extracts from A. vera, G. barbadense, M. charantia, M. paradisiaca, and S. reticulata inhibited cell growth at IC50 values of 100 to 400 μg/mL, whereas the remaining samples were hardly cytotoxic (IC50 values > 1,000 μg/mL). However, only the extracts from G. barbadense and M. paradisiaca caused appreciable DNA damage, viz. 40 and 30%, respectively. CONCLUSIONS: Preparations from G. barbadense and M. paradisiaca should be used with caution, particularly by pregnant women. These samples are now further evaluated in more comprehensive models of genotoxicity.

Spasmogenic effect of a Solanummelongena leaf extract on guinea pig tracheal chains and its possible mechanism(s).

The methanol extract of fresh leaves of Solanum melongena L. (Solanaceae) was evaluated for its capacity to alter the tone of isolated, pre-contracted guinea pig tracheal chains, as well as for its possible mechanism(s) of action. Using serial dilutions between 0.0025 and 2.5 mg/mL, the extract was found to cause a dose-dependent increase in the force of muscle contraction. The EC(50) value was 0.46 +/- 0.01 mg/mL. The concomitant use of acetylcholine 10(-5) M did not significantly affect the force of contraction induced by the extract. Histamine 10(-5) M added at about 40% to, and salbutamol 10(-6) M antagonized by about 30% its constrictive effect. Chlorpheniramine 10(-6) M, propanolol 10(-5) M, and nifedipine 10(-6) M did not significantly influence the extract-induced force of contraction, but atropine 3 x 10(-7) M reduced it by approximately 60%. These data suggest that the Solanum melongena extract exerted a bronchospasmogenic rather than a bronchospasmolytic effect, probably through muscarinic receptor stimulation.

The functional state of the isolated rabbit kidney perfused with autologous blood.

This report describes the technique and procedure for perfusing an isolated rabbit kidney with 25 ml heparinized autologous blood in a closed circuit including a pump and an oxygenator. The duration of the operative ischaemia was 5-8 min; the perfusion lasted 2.5 hours. An additional infusion was made to compensate for urinary losses. Renal blood flow increased progressively from 2.01+/-0.1 to 2.65+/-0.22* ml/g kidney weight (kw) per min (*P<0.05). Between the first (P1) and the last (P4) urine collection period the glomerular filtration rate (GFR) fell from 288+/-25 to 217+/-38* microl/g kw per min, urine flow from 5.58+/-1.13 to 4.91+/-0.75 microl/g kw per min, Na+ excretion from 1.07+/-0.19 to 0.63+/-0.12* micromol/g kw per min, K+ excretion from 0.46+/-0.03 to 0.28+/-0.05* micromol/g kw per min, P excretion from 2.5+/-0.2 to 2.0+/-0.5 microg/g kw per min, Ca excretion from 0.4+/-0.1 to 0.12+/-0.05* microg/g kw per min, creatinine excretion from 6.94+/-0.32 to 5.68+/-0.54 microg/g kw per min, glucose excretion from 18.2+/-3.2 to 1.6+/-0.5* microg/g kw per min, the free water clearance (CH2O) from -6.57+/-0.85 to -5.10+/-1.31 microl/g kw per min and urine osmolality from 600+/-52 to 590+/-105 mOsm/kg, urea excretion from 0.75+/-0.16 to 0.95+/-0.13 micromol/g kw per min. Excretion of glucose, P or Ca was observed only above a given plasma threshold value, and no transport maximum was found for glucose or P. Ca reabsorption paralleled the Na reabsorption. The proximal tubule pressure, measured within the 1st h of perfusion, was 12.5+/-1.1 mm Hg. Histological examination at the end of the perfusion showed dilatation of the tubules as in the non-perfused kidneys, and the presence of numerous bacteria. Hypertonic urine (380-1110 mOsm/kg) was observed in the presence of vasopressin, in the latter's absence the urine was hypotonic urine (206-278 mOsm/kg). There was no correlation between renal plasma flow and the GFR. CH2O increased with increasing filtered Na+ load. In conclusion, the blood-perfused, isolated rabbit kidney has a fairly constant functional capacity for approximately 2 h.