The protective effects of natural products on blood-brain barrier breakdown.

The blood-brain barrier (BBB) is a protective fence between the central nervous system and the systemic circulation, and is essential for maintaining the normal homeostasis of the central nervous system. BBB breakdown is instigated in many neurological disorders such as Alzheimer's disease and multiple sclerosis. Recent literature has advanced the knowledge on the physiology and pathophysiology of BBB breakdown, including the attribution of detrimental inducers and signalling transduction cascades. Natural products, such as flavonoids, phenolic compounds, terpenes, alkaloids, lipids and phthalides have been reported to attenuate many neurological diseases by modulating the signalling transduction cascades associated with BBB breakdown. Understanding the activities of these natural products through the molecular mechanisms associated with BBB breakdown will offer considerable scope in the discovery and development of novel agents for preventing BBB breakdown and thus, the progression of neurological disorders.

Indirect biochemical evidence that reserpine methiodide produces selective depletion of peripheral biogenic amines in rats.

Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In the present investigation, reserpine methiodide (RMI), a quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats and compared with reserpine. The 24 h urinary excretion of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the respective metabolites of noradrenaline, serotonin and dopamine were estimated and considered as indirect biochemical indices for the amine depleting action of reserpine and RMI. The results indicate that RMI at doses of equal to and double the equimolar doses of reserpine was found to deplete the peripheral amines without affecting the central stores of the amines. The results further suggest that the quaternization of reserpine might restrict its transfer across the blood-brain barrier and could be the reason for its selective peripheral action.

Evaluation of hypoglycemic and antihyperglycemic effects of Datura metel (Linn.) seeds in normal and alloxan-induced diabetic rats.

The seed powder of Datura metel was tested for its hypoglycemic activity in normal and alloxan-induced diabetic rats. Graded doses (25, 50 and 75 mg/kg, p.o.) of the seed powder when given to both normal and diabetic rats produced significant reduction in blood glucose at the 8 h. The effect was found to be dose dependent with all treatments at the doses administered.

Ras farnesyltransferase inhibition: a novel and safe approach for cancer chemotherapy.

The 21-kDa Ras proteins are well known for their regulatory role in oncogenic, mitogenic, and developmental signaling pathways. GTP activated Ras interacts directly with the Raf protein to recruit the MAP kinases and their subordinates. Attachment of Ras protein to the plasma membrane that requires farnesylation by farnesyl pyrophosphate at its C-terminus, is essential for its biological activity. Ras oncogenes are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. A promising pharmacological approach of antagonizing oncogenic Ras activity is to develop inhibitors of farnesyl transferase. These inhibitors may be useful in blocking the action of Ras onco-proteins.