5-Geranyloxy-7-methoxycoumarin inhibits colon cancer (SW480) cells growth by inducing apoptosis.

For the first time, three coumarins were isolated from the hexane extract of limes (Citrus aurantifolia) and purified by flash chromatography. The structures were identified by NMR (1D, 2D) and mass spectral analyses as 5-geranyloxy-7-methoxycoumarin, limettin, and isopimpinellin. These compounds inhibited human colon cancer (SW-480) cell proliferation, with 5-geranyloxy-7-methoxycoumarin showing the highest inhibition activity (67 %) at 25 µM. Suppression of SW480 cell proliferation by 5-geranyloxy-7-methoxycoumarin was associated with induction of apoptosis, as evidenced by annexin V staining and DNA fragmentation. In addition, 5-geranyloxy-7-methoxycoumarin arrested cells at the G0/G1 phase, and induction of apoptosis was demonstrated through the activation of tumour suppressor gene p53, caspase8/3, regulation of Bcl2, and inhibition of p38 MAPK phosphorylation. These findings suggest that 5-geranyloxy-7-methoxycoumarin has potential as a cancer preventive agent.

Bioactive compounds from Mexican lime ( Citrus aurantifolia ) juice induce apoptosis in human pancreatic cells.

Lime (Citrus aurantifolia Swingle) is one of the major citrus fruits and widely consumed, but there is limited evidence about its health-promoting properties. Hence, an investigation was conducted to understand the chemopreventive effects of lime juice on pancreatic cancer cells and the possible mechanism for induction of apoptosis using Panc-28 cells. Freeze-dried lime juice was extracted with different solvents, such as chloroform, acetone, MeOH, and MeOH/water (8:2). The chloroform extract showed the highest (85.4 and 90%) radical-scavenging activity by 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) methods at 624 microg/mL, whereas the MeOH/water extract showed the lowest (<20%) activity. The active components were identified by high-performance liquid chromatography (HPLC) using a C-18 column as rutin, neohesperidin, hesperidin, and hesperitin. Furthermore, the limonoids identified are limonexic acid, isolimonexic acid, and limonin. All of the extracts of lime juice inhibited Panc-28 cancer cell growth. The MeOH extract exhibited the maximum activity, with an IC50 value of 81.20 microg/mL after 72 h. The inhibition of Panc-28 cells was in the range of 73-89%, at 100 microg/mL at 96 h. The involvement of apoptosis in induction of cytotoxicity was confirmed by expression of Bax, Bcl-2, casapase-3, and p53. The results of the present study clearly indicate that antioxidant activity is proportionate to the content of flavonoids and proliferation inhibition ability is proportionate to the content of both flavonoids and limonoids.

Effect of felodipine on cholinergic responses of the colonic smooth muscle of streptozotocin induced diabetic rats.

In streptozotocin induced diabetic rats, irrespective of felodipine treatment (5 mg/kg/day po for 4 weeks), a reduction in contractile response of colonic smooth muscle in vitro was observed. Similarly, in both control and diabetic rats treated with felodipine, contractile response was reduced. However, in felodipine treated diabetic rats there was a significant increase in response to exogenous acetylcholine. It may be of interest to study the effect of felodipine, on gastro-intestinal motility in vivo in diabetic rats, to enable extrapolation of the present results to the effect of felodipine on gastrointestinal complications of diabetes mellitus.

Effect of felodipine on myocardial function and cholinergic responses in short term streptozotocin diabetes in rats.

Cardiovascular complications of diabetes mellitus account for 80% of deaths among diabetics. Autonomic neuropathy increases the susceptibility of the diabetic myocardium to arrhythmias. Decreased contractility of diabetic myocardium is associated with intracellular calcium overload. However, the relationship between calcium levels and myocardial cholinergic responses is not known. This study was undertaken to observe the effect of felodipine 5 mg/kg on myocardial function and cholinergic responses of the spontaneously working isolated heart of rats with short term streptozotocin-diabetes. Felodipine was administered (po) for 4 week to rats with streptozotocin-diabetes of 4 week duration. Felodipine did not alter the blood glucose levels. The increased cardio-somatic ratio in diabetic rats was attenuated by felodipine. Diabetic status was associated with decreased coronary flow and felodipine increased coronary flow in diabetic rat hearts both before and after ACh. It may be concluded that felodipine favourably altered the adverse myocardial pathology in experimental diabetes, and this strengthens its use as an antihypertensive in diabetics.

Effect of felodipine on serum lipid profile in short term streptozotocin-diabetes in rats.

Lipid lowering effect of calcium antagonists is well documented in high fat fed rats and in hypertensive patients. In order to study their effect on lipid profile in experimental diabetes, felodipine 5 mg/kg/day per oral for 4 week was given to rats with streptozotocin-diabetes of 8 week duration. Serum total cholesterol and triglycerides were estimated in non-fasting rats at the end of the study period using Ranbaxy diagnostic kits. Diabetic rats had a significant elevation of both total cholesterol and triglycerides. In diabetic rats felodipine treatment produced a significant reduction of the serum triglycerides while there was no change in the serum total cholesterol. In control rats the drug did not produce any significant alteration in the levels of both total cholesterol and triglycerides.