Pharmacological properties and identification of cardiotonic principles from the Indian snuff, Maquira sclerophylla, Ducke

The powdered bark obtained from Maquira sclerophylla Ducke is a snuff used by Amazonian natives. Pharmacological studies on rodents, guinea-pigs, rabbits and dogs revealed cardiovascular changes as the major effects produced by the polar phase of the bark ethanol extract, Oriented by this pharmacological activity a cardenolide fraction was chemically purified from the crude extract. Both crude extract and the purified fraction produced a positive inotropic effect in isolated heart preparations from guinea-pigs and rabbits, and inhibited the Na+, K+-ATPase activity of the enzyme isolated from bovine ventricles. The fraction yielded two major purified cardenolides identified as Maquiroside A (C30H46O8) and Cymarin (C30H44O9). Simultaneous intracellular recordings of the resting membrane potential (RMP) and miniature endplate potentials in rat diaphragm muscle fibres showed that the effect of the purified fraction predominated on the motor nerve terminals enhancing the spontaneous transmitter release, without major changes of RMP values. Comparatively, the effect of ouabain prevailed on the muscle fibre membrane. Considering that both effects depend on the Na+, K+-ATPase activity, the results indicated that the compounds derived from Maquira exert differential actions on this enzyme in the nerve and muscle membrane. These observations may explain the use of this toxic snuff in native festivities. (C) 1997 by John Wiley & Sons, Ltd.11213614

Tissue elasticity and the ageing elastic fibre

The ability of elastic tissues to deform under physiological forces and to subsequently release stored energy to drive passive recoil is vital to the function of many dynamic tissues. Within vertebrates, elastic fibres allow arteries and lungs to expand and contract, thus controlling variations in blood pressure and returning the pulmonary system to a resting state. Elastic fibres are composite structures composed of a cross-linked elastin core and an outer layer of fibrillin microfibrils. These two components perform distinct roles; elastin stores energy and drives passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signalling, maintain tissue homeostasis via TGFβ sequestration and potentially act to reinforce the elastic fibre. In many tissues reduced elasticity, as a result of compromised elastic fibre function, becomes increasingly prevalent with age and contributes significantly to the burden of human morbidity and mortality. This review considers how the unique molecular structure, tissue distribution and longevity of elastic fibres pre-disposes these abundant extracellular matrix structures to the accumulation of damage in ageing dermal, pulmonary and vascular tissues. As compromised elasticity is a common feature of ageing dynamic tissues, the development of strategies to prevent, limit or reverse this loss of function will play a key role in reducing age-related morbidity and mortality