Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and in vivo modulation of biomarkers of chemoprevention in the hamster buccal pouch carcinogenesis model.

We evaluated the chemopreventive potential of Azadirachta indica (neem) leaf fractions based on in vitro antioxidant assays, and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. In addition we also identified the major constituents in neem leaf fractions by HPLC. Analysis of the free radical scavenging activities and reducing potential of crude ethanolic extract (CEE), ethyl acetate fraction (EAF) and methanolic fraction (MF) of neem leaf revealed a concentration-dependent increase in antioxidant potential that was in the order EAF>MF>CEE. Administration of neem leaf fractions reduced the incidence of DMBA-induced HBP carcinomas at a lower concentration compared to the crude extract. Chemoprevention by neem leaf fractions was associated with modulation of phase I and phase II xenobiotic-metabolising enzymes, lipid and protein oxidation, upregulation of antioxidant defences, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. However, EAF was more effective than MF in terms of antiproliferative and antiangiogenic effects, and expression of CYP isoforms. The greater efficacy of EAF may be due to higher content of constituent phytochemicals as revealed by HPLC analysis. The results of the present study suggest that the antioxidant properties of neem leaf fractions may be responsible for modulating key hallmark capabilities of cancer cells such as cell proliferation, angiogenesis and apoptosis in the HBP carcinogenesis model.

In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (-)-cromakalim, ZD6169 and WAY-133537 in rats.

OBJECTIVE: To compare in vivo the potency and bladder-vascular selectivity of ATP-sensitive potassium channel openers (KCOs) (-)-cromakalim, WAY-133537 and ZD6169 and a muscarinic antagonist, tolterodine in rats. MATERIALS AND METHODS: Bladder and arterial pressures were monitored simultaneously, before and after increasing intravenous doses of compounds, in each of two urethane-anaesthetized rat bladder hyperactivity models: spontaneous non-voiding myogenic contractions secondary to partial outlet obstruction and volume-induced neurogenic contractions. RESULTS: (-)-Cromakalim, WAY-133537 and ZD6169 caused a dose-dependent suppression of spontaneous contractions in the obstructed model, with a 50% inhibition of the contraction area under the curve at doses of 0.06, 0.14 and 2.4 micro mol/kg (intravenous), respectively. Corresponding decreases in mean arterial pressure at these effective doses were 24%, 15% and 15%, respectively. The KCO potency rank order was the same and their relative potency highly comparable in the neurogenic model. There was complete inhibition of spontaneous contractions in obstructed rats at doses corresponding to approximately 50% inhibition of the neurogenic contractions. While tolterodine caused a dose-dependent inhibition of contractions in the neurogenic model, it was ineffective at inhibiting non-voiding contractions in obstructed rats. CONCLUSIONS: All KCOs tested caused significant decreases in arterial pressure at doses effective on the bladder in the model of obstructive instability, suggesting a lack of bladder-vascular selectivity. Similar KCO potency in both assays suggests no appreciable changes in KATP channel function as a result of partial outlet obstruction.

The role of unsaponifiable components in the lipidemic property of olive oil.

Pure olive oil triglycerides (POLO), free from all unsaponifiable matter, were isolated from Virgin Spanish olive oil (COLO) by alumina-charcoal column chromatography. COLO and POLO were used as sources of dietary fat in two animal studies. The responses of serum and liver lipids to the two types of dietary fat were examined. Our results show that animals fed POLO-diet gave somewhat higher serum total and LDL cholesterol levels as compared to those on COLO-diet. The increase in serum cholesterol level is followed by a parallel increase in liver cholesterol content. These results indicate that the hypocholesterolemic effect of olive oil was partly due to the presence of the unsaponifiable matter. Supplement of the POLO-diet separately with a-tocopherol and squalene resulted in serum lipid responses similar to that observed with the COLO-diet. The serum and liver triglyceride levels are not affected by the removal of unsaponifiable components but addition of a--T and squalene to the POLO-diet appeared to lower both the cholesterol and triglyceride levels in the serum but increased only the liver cholesterol content. These results show that the unsaponifiable components modulate the hypocholesterolemic effect of olive oil.

Effect of papaya (Carica papaya linn) on pregnancy and estrous cycle in albino rats of Wistar strain.

The antifertility effects of Carica papaya were investigated by feeding adult cycling and pregnant rats with different components of its fruits. No attempt was made to force-feed the animals. The results indicate that unripe fruits of papaya interrupt estrous cycle and induce abortions. The abortifacient property seems to decrease as the fruit becomes stale or ripe. Exogenous progesterone counteracts partially the adverse effects on pregnancy and the surviving foeti are without any distinct malformations.