Metabolic and molecular action of Trigonella foenum-graecum (fenugreek) and trace metals in experimental diabetic tissues.

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmacokinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and antihyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.

Physiological and biochemical effects of 17ß estradiol in aging female rat brain.

Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 µg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders.

A metabolic and functional overview of brain aging linked to neurological disorders.

Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.

Lipid induced conformation of the tachykinin peptide Kassinin.

Both the aqueous and lipid-induced structure of Kassinin, a dodecapeptide of amphibian origin, has been studied by two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy and distance geometry calculations. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The distance constraints obtained from the NMR data have been utilized in a distance geometry algorithm to generate a family of structures, which have been refined using restrained energy minimization and dynamics. These data show that, while in water Kassinin prefers to be in an extended chain conformation, in the presence of perdeuterated dodecylphosphocholine (DPC) micelles, a membrane model system, helical conformation is induced in the central core and C-terminal region (K4-M12) of the peptide. N-terminus though less defined also displays some degree of order and a possible turn structure. The conformation adopted by Kassinin in the presence of DPC micelles is consistent with the structural motif typical of neurokinin-1 selective agonists and with that reported for Eledoisin in hydrophobic environment.

Effect of pH and inorganic carbon concentration on growth, glycerol production, photosynthesis and dark respiration of Dunaliella salina.

The growth of Dunaliella salina was studied with respect to pH and varying concentrations of NaHCO3 in the medium. The growth rate, photosynthesis and dark respiration were maximal at pH 8 and 4 mM NaHCO3 in the medium. Photosystem I of the Hill reaction was affected more by inorganic carbon concentration than photosystem II.

Regulation of Gi by the CB1 cannabinoid receptor C-terminal juxtamembrane region: structural requirements determined by peptide analysis.

A CB1 cannabinoid receptor peptide fragment from the C-terminal juxtamembrane region autonomously inhibits adenylyl cyclase activity in a neuroblastoma membrane preparation. The cannabinoid receptor antagonist, SR141716A, failed to block the response. The peptide was able to evoke the response in membranes from Chinese hamster ovary (CHO) cells that do not express the CB1 receptor. These studies are consistent with a direct activation of Gi by the peptide. To test the importance of a BXBXXB sequence, Lys403 was acetylated, resulting in a peptide having similar affinity but reduced efficacy. N-Terminal truncation of Arg401 resulted in a 6-fold loss of affinity, which was not further reduced by sequential truncation of up to the first seven amino acids, four of which are charged. N-Terminal-truncated peptides exhibited maximal activity, suggesting that Gi activation can be conferred by the remaining amino acids. Truncation of the C-terminal Glu417 or substitution of Glu417 by a Leu or of Arg401 by a Norleucine reduced activity at 100 microM. The C-terminal juxtamembrane peptide was constrained to a loop peptide by placement of Cys residues at both terminals and disulfide coupling. This modification reduced the affinity 3-fold but yielded near-maximal efficacy. Blocking the Cys termini resulted in a loss of efficacy. Circular dichroism spectropolarimetry revealed that all C-terminal juxtamembrane peptide analogues exist in a random coil conformation in an aqueous environment. A hydrophobic environment (trifluoroethanol) failed to induce alpha-helix formation in the C-terminal juxtamembrane peptide but did so in less active peptides. The anionic detergent sodium dodecyl sulfate induced alpha-helix formation in all analogues except the loop peptide, where it induces a left-handed PII conformation. It is concluded that alpha-helix formation is not required for Gi activation.

Lipid-induced conformation of substance P.

Both the aqueous and the lipid-induced structure of a representative and widely studied tachykinin, substance P, has been investigated by two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy and distance geometry calculations. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (COSY and TOCSY) experiments and Overhauser enhancement spectroscopy (ROESY and NOESY; experiments. The NMR data obtained were utilized in a distance geometry algorithm to generate a family of structures which were further refined using restrained energy minimization. These data show that, while in water substance P appears to favour an extended chain conformation, in the presence of perdeuterated dodecylphosphocholine (DPC) micelles as membrane model system an amphiphilic helical conformation is induced in the mid-region (Q5-Q8) of substance P. The conformation adopted by substance P in the presence of DPC micelles yields a structural motif typical of neurokinin-1 selective ligands, as proposed by Convert and coworkers (O. Convert et al., Neuropeptides 19, 259-270 (1991)).