bluuebunny/crossref_metadata_2025 huggingface dataset:
Olea europaea L. and oleuropein: Effects on excito‐conduction and on monophasic action potential in anaesthetized dogs
Authors: Occhiuto F. , Circosta C. , Gregorio A. , Busa G.
Published: October 2006

The effects of a glyceroethanolic macerate of the leaves of Olea europaea L. and of oleuropein on excito‐conduction and on the right atrial and ventricular monophasic action potential (MAP) have been studied in anaesthetized dogs using the technique of endocavitary recording. At the higher doses tested, a slight increase in the sinusal cycle of the sinoatrial conduction time and of the sinus node recovery time, together with a prolongation of the atrioventricular and intraventricular conduction and an increase of the atrial and ventricular MAP duration were observed. This may be due to a decrease in the repolarization phase 3. These electrophysiological effects indicate an inhibitory action both on the swift influx of sodium and on the slow influx of calcium, as well as a decrease in potassium conductance.
Chemical and pharmacological analysis of the crude aqueous/alcoholic extract from Cordyline dracaenoides
Authors: Calixto João B. , de Lima Thereza C. M. , Morato Gina S. , Nicolau Mauro , Takahashi Reinaldo N. , Valle Rosa M. R. , Schmidt Carla C. , Yunes Rosendo A.
Published: October 2006

Chemical analysis of Cordyline dracaenoides (Kunth) demonstrated the presence of steroidal saponins and anthocyanidins in the stem, rhizome and root. Small amounts of tannins were also detected in its stem and rhizome. Pharmacological analysis revealed different effects according to the part of the plant used. Crude aqueous/alcoholic extract (CE) from the rhizome inhibited carrageenan‐induced rat paw oedema, while the CE obtained from the root significantly decreased the locomotor activity and potentiated barbiturate‐induced hypnosis in mice. The CE from the roots inhibited noradrenaline‐induced contraction in the rat vas deferens in a concentration‐dependent and a noncompetitive manner, while the CE from the rhizome caused a parallel displacement to the left of noradrenaline concentration response curves. In the isolated rat stomach, the CE from the roots promoted a concentration‐dependent displacement to the right of the serotonin concentration response curve allied to a marked inhibition of its maximal response, while the CE from the rhizome produced only an inhibition of about 40% of serotonin‐contractile responses. These results suggest that the CE from C. dracaenoides exhibits a potent and long lasting antioedematogenic effect, has central depressant effects and potentiates noradrenaline‐induced contractile responses of the isolated rat vas deferens. All these effects may be, at least in part, related to the presence of steroidal saponins in this plant.
Hypotensive action of Solanum melongena on normotensive rats
Authors: Shum O. L. , Chiu K. W.
Published: October 2006

The cardiovascular action of Solanum melongena extract (SME) was investigated using in vivo and in vitro preparations. SME produced dose‐dependent hypotensive responses in normotensive albino rats. The duration of response was also dose dependent. In pharmacological antagonist studies, the hypotensive action of SME was proved not to be mediated through the autonomic ganglion, the α‐adrenoceptor or the histaminergic receptor. SME worked via the β‐adrenoceptor and cholinergic (muscarinic) receptor inducing the hypotensive response. A dose‐related attenuation of hypotension with increasing dosages of the β‐adrenoceptor blocker, propranolol, and the cholinergic receptor blocker, atropine was observed. In vitro studies indicated that the vasorelaxing and negative inotropic effect of SME might be implicated in the hypotensive response. The activities of the β‐adrenergic and acetylcholine receptors mediated by SME in turn promoted vasodilation of the resistant vessels and a reduction in cardiac activity respectively. It is also possible that the hypotensive effect of SME could be accounted for by its influence on the activity of the renin‐angiotensin system, since a significant difference of the hypotensive response of SME was obtained with captopril. Furthermore, SME induced diuresis in water‐loaded rats which might also account for the hypotensive effect observed. SME could be a very potent hypotensive agent.
Effects of Ganoderma applanatum polysaccharide on cellular and humoral immunity in normal and sarcoma 180 transplanted mice
Authors: Bin Gao , Gui‐Zhen Yang
Published: October 2006

Ganoderma applanatum polysaccharide (GAPS) was extracted and purified from Polyporaceae Ganoderma applanatum (Pers.) Pat. It was found that in vitro GAPS (65.2–250 μg/mL) increased the spleen cell proliferation response to ConA; GAPS (500 μg/mL) enhanced IL‐2 production of spleen cells stimulated with ConA; GAPS (125–500 μg/mL) augmented the IFNγ production of spleen cells stimulated with ConA. Administering GAPS (20 mg/kg/day s.c.) to normal mice for 10 consecutive days enhanced spleen cell proliferation responses to ConA and the IL‐2 and IFNγ production of spleen cells stimulated with 5 μg/mL ConA. It also increased spleen cell primary antibody responses to sheep red blood cells. Administering GAPS (20 mg/kg/day, s.c.) to sarcoma 180 transplanted mice for 15 consecutive days restored the NK activity and the IL‐2 and IFNγ production of the spleen cells which were suppressed by the tumour.
Hypolipidaemic effect of fenugreek seeds. A clinical study
Authors: Sharma R. D. , Raghuram T. C. , Rao V. Dayasagar
Published: October 2006

The hypolipidaemic effect of fenugreek seeds (Trigonella foenum graecum L.) was evaluated in ten hyperlipidaemic subjects. Isocaloric diets with and without fenugreek were each given for 20 days. Ingestion of experimental diets, containing 100 g of debitterized fenugreek powder, resulted in a significant reduction in the serum total cholesterol, LDL and VLDL cholesterol and triglyceride levels. HDL cholesterol levels were not altered but the ratio with total cholesterol and LDL and VLDL cholesterol were significantly increased. These results indicate the beneficial effect of fenugreek seeds in hyperlipidaemic patients.
Virucidal activity in aqueous extracts obtained from Cedrela tubiflora leaves
Authors: Córdoba Mónica A. , Coto Celia E. , Damonte Elsa B.
Published: October 2006

Crude extracts obtained from leaves of Cedrela tubiflora (CT) (Meliaceae family) show antiviral and virucidal effects against several viruses. Herpes simplex, pseudorabies and vesicular stomatitis viruses were extremely susceptible and a reduction of 3–5 log in infectivity occurred after 15 min of direct incubation with the plant extract. By contrast, poliovirus and the Tacaribe arenavirus are inhibited intracellularly. The inhibitory action is dose dependent and no cytotoxic effects were detected on Vero cells after 2 days of CT treatment.
Cytotoxic and antitumour activity of scopadulcic acid from Scoparia dulcis L.
Authors: Hayashi Kyoko , Hayashi Toshimitsu , Morita Naokata
Published: October 2006

Scopadulcic acid B is a diterpenoid recently isolated from Scoparia dulcis L. This compound showed greater cytotoxicity against cell lines derived from tumour tissues with a 50% inhibitory concentration (IC50) of 0.068–0.076 μg/mL, compared with cell lines from normal tissues with an IC50 of 0.097–0.245 μg/mL. The in vivo antitumour activity of scopadulcic acid B was determined using mice inoculated with Ehrlich ascites tumour cells. Oral administration of the compound at doses of 25 or 100 mg/kg/day prolonged the median survival time of the animals. However, when administered intraperitoneally to mice at doses of 25, 50 or 100 mg/kg/day, scopadulcic acid B increased the survival rate by 12.5%, 12.5% and 25%, respectively, without weight change over the treatment period.
Fagaronine, a novel antileukaemic alkaloid
Authors: Barret Y. , Sauvaire Y.
Published: October 2006

A review is presented about fagaronine, a benzophenanthridine alkaloid responsible for antitumoural activity. Plant source, extraction, biosynthesis, medicinal properties, especially antileukaemic activity, are described.
In vitro antibacterial activity of the volatile oil of Nigella sativa seeds against multiple drug‐resistant isolates of Shigella spp. and isolates of Vibrio cholerae and Escherichia coli
Authors: Ferdous A. J. , Islam S. N. , Ahsan M. , Hasan C. M. , Ahmed Z. U.
Published: October 2006

The antibacterial activity of the volatile oil of Nigella sativa seeds was studied against 37 isolates of Shigella dysenteriae 1, Shigella flexneri, Shigella sonnei and Shigella boydii and 10 strains of Vibrio cholerae and Escherichia coli. Most of the strains were clinically resistant to ampicillin, co‐trimoxazole and tetracycline. All the strains tested showed promising sensitivity to the volatile oil. The minimum inhibitory concentration (MIC) of the volatile oil for Shigella, Vibrio and Escherichia strains tested was between 50–400 μg/mL.
Effect of Shilajit on rat brain monoamines
Authors: Bhattacharya S. K. , Ghosal S.
Published: October 2006

Shilajit (25 and 50 mg/kg i.p. for 5 days) significantly lowers the levels of 5HT and 5HIAA and increases the levels of DA, NA and their metabolites, in concert, in rat brain. The finding is appraised in view of its use as an Ayurvedic rasayan (rejuvenator).
Pharmacological properties of a lyophilizate from Galeopsis ladanum on the central nervous system of rodents
Authors: Czarnecki R. , Librowski T. , Zélbala K. , Kohlmünzer S.
Published: October 2006

The influence of a fraction obtained from Galeopsis ladanum L. on the central nervous system of rodents was examined. The results of these investigations show that the fraction impeded CNS activity. It is practically nontoxic and at a dose of 2000 mg/kg i.p. it does not have a soporific influence on mice. It reduces considerably the spontaneous locomotor activity of mice as well as the locomotor activity of mice stimulated by caffeine, but did not influence the locomotor activity induced by amphetamine. The extract did not exhibit a synergetic effect with barbiturates. The results suggest that the pharmacological activity of the extract resembled the activity of drugs which generally depress the CNS, being on the border between ataractic and sedative drugs.
Impact of the preparation process on immunomodulatory activities of the ayurvedic drug Nimba arishta
Authors: Kroes B. H. , Van Den Berg A. J. J. , Labadie R. P. , Abeysekera A. M. , De Silva K. T. D.
Published: October 2006

Nimba arishta is an ayurvedic drug obtained by fermentation of a decoction of Azadirachta indica bark to which sugar and a kalka have been added. Kalkas consist of various plant materials including flowers of Woodfordia fruticosa. The effects of the preparation process on immunomodulatory properties of Nimba arishta were investigated by means of model systems. On the basis of traditional applications of Nimba arista in Sri Lanka, complement activity and functioning of granulocytes were selected as relevant immunological parameters in our studies. Long boiling times, as a consequence of decoction preparation on a commercial scale, were found to substantially reduce the immunomodulatory activities, whereas addition of the kalka resulted in a marked increase. Inoculation with yeasts (Saccharomyces cerevisiae or Schizosaccharomyces pombe var. pombe) or microorganisms introduced through addition of the kalka did not affect the in vitro immunomodulatory activities of Nimba arista. Further investigations revealed that Woodfordia fruticosa is the kalka ingredient with the most pronounced biological activities. Although in quantitative terms the bark of Azadirachta indica strongly dominates in Nimba arishta preparation, it was shown by detailed model studies that the flowers of Woodfordia fruticosa were found to represent a major ingredient with respect to modulation of complement activity.
An extract of the leaves of the breadfruit Artocarpus altilis (parkinson) fosberg exerts a negative inotropic effect on rat myocardium
Authors: Young Ronald E. , Williams Lawrence A. D. , Gardner Michael T. , Fletcher Cyril K.
Published: October 2006

Ethyl acetate soluble extracts from the leaves of the breadfruit Artocarpus altilis exerted a weak, negative chronotropic effect (p<0.05) and significantly reduced left ventricular pulse pressure (p<0.001) in vivo in the rat. The electrocardiogram maintained a high amplitude QRS complex (ventricular excitation) even when the ventricular pressure pulse was very depressed. On right ventricular myocardial strips, the same extracts produced a significant negative inotropic effect (p<0.0001). This indicates that the in vivo effects might be due in part, to a direct inotropic effect on the myocardium. An in vivo side effect was extensive intravascular haemolysis and consequent haemoglobinuria which could be caused by the vehicle, the extract, or a combined effect of the two. The mechanism of action of the inotropic agent was not cholinergic, and may involve a decoupling of excitation and contraction.
Oligo‐ and macrocyclic diterpenes in thymelaeaceae and euphorbiaceae occurring and utilized in Yunnan (Southwest China) 5. Daphnane type diterpene 9,13,14‐orthoesters from roots of Daphne papyracea
Authors: Dagang Wu , Sorg B. , Adolf W. , Opferkuch H. J. , Hecker E.
Published: October 2006

From roots of Daphne pupyracea Wall, two new diterpene esters, Daphne factors P1 and P2, were isolated. Both are esters of the polyfunctional daphnane type: P1 is the 9,13,14‐orthobenzoate‐12‐(2E,4E,6E‐decatrienoate) of 6a,7a‐epoxy‐5β, l2β‐dihydroxyresiniferonol. P2 is structurally nearly identical with P1, the only difference is located in the parent alcohol moiety: that of P1 carries an olefinic Δ1,2 unsaturation whereas P1 exhibits the 1,2α‐dihydro partial structure.
Recent advances in studies of antihyperlipaemic and antihyperglycaemic compounds from Chinese traditional and herbal medicines
Authors: Ling‐Hua Zhang , Pei‐Gen Xiao
Published: October 2006

Recent advances concerning the studies of Chinese traditional and herbal medicine with antihyperlipaemic and antihyperglycaemic properties have been reviewed; their medicinal plant sources and the molecular structures of the active compounds therein, as well as the result of their pharmacological and biochemical studies, wherever available, are presented.
Garlicin—fact or fiction? the antibiotic substance from garlic (Allium sativum L.)
Authors: Koch Heinrich P.
Published: October 2006

It was in the early pioneer days of the antibiotic era when ‘garlicin’, the antibiotic agent from garlic (Allium sativum L.), appeared for the first time in the scientific literature and was described as a substance isolated from garlic cloves with convincing pharmacological and clinical evidence concerning its antibiotic properties. In this article evidence for and against garlicin as a chemical entity will be reviewed in order to clarify more fully the known antibiotic activity of garlic clove extracts.
Antioedema and analgesic actions of Diodia scandens extract in rats and mice
Authors: Akah P. A. , Okogun J. I. , Ekpendu T. O.
Published: October 2006

An extract of Diodia scandens obtained by petroleum ether extraction of the leaves was screened for pharmacological actions. The extract evinced a marked antiinflammatory effect in rats, causing a dose‐related and sustained inhibition of the increase in rat paw circumference caused by subplantar injection of a phlogistic agent. In addition, the extract increased the threshold of pain stimulus in mice. The extract significantly protected rats from aspirin, indomethacin and reserpine induced ulcers. These results revealed that the plant, Diodia scandens has potential medicinal value.
Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine
Authors: Da Silva B. A. , De Araújo Filho A. P. , Mukherjee R. , Chiappeta A. De A.
Published: October 2006

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea‐pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca2+ channels. For example in guinea‐pig ileum, bisnordihydrotoxiferine (pD'2 3.92±0.09) and verapamil (pD'2 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'2 4.37±0.02) and verapamil (pD'2 6.83±0.10) also antagonized CaCl2 induced contractions of K+‐depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca2+ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC50, 6.10 × 10−6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC50, 2.30 × 10−5M), a known inhibitor of the release of Ca2+ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.
Antidiarrhoeal activity of the methanolic fraction of the extract of unripe fruits of Psidium guajava Linn.
Authors: Ghosh T. K. , Sen T. , Das Arunima , Dutta A. S. , Nag Chaudhuri A. K.
Published: October 2006

The methanolic fraction of the extract of unripe fruits of Psidium guajava was found to possess significant antidiarrhoeal activity. The fraction decreased gastric motility in an experimental animal model and inhibited acetylcholine release from isolated guinea‐pig ileum. On microbial screening the fraction was found to inhibit significantly the growth of different strains of Shigella spp. and Vibrio cholerae.
Toki‐Shakuyaku‐San and Oren‐Gedoku‐To improve the disruption of spatial cognition induced by cerebral ischaemia and central cholinergic dysfunction in rats
Authors: Fujiwara Michihiro , Iwasaki Katsunori
Published: October 2006

The effects of traditional Kampo prescriptions, Toki‐Shakuyaku‐San and Oren‐Gedoku‐To, were compared on the improvement of experimental disruption of spatial cognition using an eight‐arm radial maze task in rats. These two Kampo prescriptions, Toki‐Shakuyaku‐San at a dose of 100 and 200 mg/kg, p.o. and Oren‐Gedoku‐To at a dose of 5 and 10 mg/kg, p.o., improved the disruption of spatial cognition in a non‐dose‐dependent manner in both scopolamine (0.5 mg/kg, i.p.) and cerebral ischaemia (10 min) treated rats. At high doses of the drugs, these ameliorative effects were diminished. These results suggest that the balance between several neurotransmitter systems may play a significant role in learning and memory performance. Ameliorative effects of Toki‐Shakuyaku‐San resulted in 50% of rats recovering to normal, in the group treated with scopolamine compared with the cerebral ischaemia group. Oren‐Gedoku‐To, on the other hand, improved the efficacy against ischaemia.
Effect of liver‐protecting Sempervivum tectorum extract on the immune reactivity of spleen cells in hyperlipidaemic rats
Authors: Blázovics Anna , González‐Cabello R. , Barta Irén , Gergely P. , Fehér J. , Kéry Ågnes , Petri G.
Published: October 2006

The pathobiological role of free radicals was demonstrated in hyperlipidaemia and in steatotic liver as well as in the immune response of lymphocytes and monocytes. Hyperlipidaemia has a suppressive effect on cellular immune responses, inhibits the mitogen induced lymphoblast transformation, diminishes the tumour necrosis factor alpha (TNF‐α) production of spleen macrophages and enhances spontaneous interleukin 1 (IL‐1) activity. A freeze dried extract of Sempervivum tectorum has antioxidant, free radical scavenger and membrane stabilizing effects. The measured serum parameters were changed favourably after Sempervivum tectorum extract treatment. The beneficial effect of Sempervivum tectorum extract was also observed on the Con A stimulated blast transformation of splenocytes, on the lipopolysaccharide (LPS) triggered TNF‐α activity and on the spontaneous IL‐1 activity of spleen macrophages of hyperlipidaemic rats. The natural scavenger capacity was increased by treatment, initiating restoration of liver function.
Effect of fenugreek seeds on intravenous glucose disposition in non‐insulin dependent diabetic patients
Authors: Raghuram T. C. , Sharma R. D. , Sivakumar B. , Sahay B. K.
Published: October 2006

The hypoglycaemic activity of fenugreek seeds (Trigonella foenum graecum) in experimental animals and humans has been well documented. Fenugreek has been shown to reduce fasting and postprandial blood glucose levels in diabetic patients. However, it is not clear whether the improvement in glucose tolerance is due to the effect of fenugreek on the absorption or metabolism of glucose. A metabolic study was carried out, and diets with or without 25 g fenugreek were given randomly to 10 non‐insulin dependent diabetics, each for 15 days, in a crossover design. An intravenous glucose tolerance test (GTT) at the end of each study period indicated that fenugreek in the diet significantly reduced the area under the plasma glucose curve (AUC), half‐life, and increased the metabolic clearance rate. In addition, it increased erythrocyte insulin receptors. These results suggest that fenugreek can improve peripheral glucose utilization which contributes to an improvement in glucose tolerance. Thus, fenugreek may exert its hypoglycaemic effect by acting at the insulin receptor as well as at the gastrointestinal level.
Volatile constituents of Xylopia frutescens, X. pynaertii and X. sericea: Chemical and biological study
Authors: Fournier G. , Hadjiakhoondi A. , Leboeuf M. , Cavé A. , Charles B. , Fourniat J.
Published: October 2006

The essential oils from three Xylopia species (X. frutescens, X. pynaertii, X. sericea), Annonaceae, have been examined by GC and GC/MS, and screened for bacteriostatic and fungistatic activities. The main components of each oil have been identified. The major constituents of X. frutescens stem bark oil were α‐cubebene (25.2%) and δ‐cadinol (27.4%). The root of X. pynaertii was rich in elemol (27.1%), while the stem bark oil contained δ‐cadinene (10.3%), γ‐muurolene (10.1%) and cubenol (12.6%). The major components of X. sericea root bark oil were p‐cymene (22.8%) and α‐gurjunene (13.8%). These oils exhibited moderate bacteriostatic and fungistatic activities.
Antiulcer effect of flavonoids. Role of endogenous PAF
Authors: Izzo A. A. , Carlo G. Di , Mascolo N. , Capasso F. , Autore G.
Published: October 2006

Quercetin, rutin and kaempferol, administered intraperitoneally (25–100 mg/kg) inhibited dose‐dependently gastric damage produced by acidified ethanol in rats. Flavone was inactive while naringin was active at higher dose (200 mg/kg). The flavonols tested inhibited dose‐dependently the mucosal content of platelet‐activating factor (PAF) suggesting that the protective effects of these substances may be mediated by endogenous PAF.
Hepatoprotective studies of a fraction from the fruits of Terminalia belerica roxb. On experimental liver injury in rodents
Authors: Anand K. K. , Singh B. , Saxena A. K. , Chandan B. K. , Gupta V. N.
Published: October 2006

The effects of an orally administered fraction (TB5) from the fruits of Terminalia belerica in experimental liver injury induced by carbon tetrachloride (CCI4) were studied. Hexobarbitone‐induced sleep, zoxazolamine‐induced paralysis, transaminases, bilirubin, total protein in serum and microsomal lipid peroxidation and triglycerides in liver were used as indices of liver injury.

A significant hepatoprotective effect was observed as evident from shortened hexobarbitone ‘sleep time’ and zoxazolamine ‘paralysis time’ when compared with CCI4 alone. Pre‐ and post‐treatment of TB5 reduced, in a dose dependent manner, the elevated levels of serum tranaminases and bilirubin in rats, thus demonstrating its effect both as a prophylactic and curative. Its protective effects on microsomal lipid peroxidation and triglycerides in liver suggest a restorative effect in the process of CCI4‐induced liver damage. TB5 did not show any signs of toxicity up to oral doses of 3.2 g/kg in mice.
Semi‐synthesis of C203H‐resiniferatoxin
Authors: Gordge Phil C. , Darcy Patricia , Evans A. Tudor , Ryves W. Jonathan , Evans Fred J. , Hassan Nahed M.
Published: October 2006

There has recently been considerable interest concerning the biochemical and pharmacological mechanisms of action of resiniferatoxin (Rx). Rx is a daphnane diterpene ester, which is part of the phorbol ester family of diterpenes. We have synthesized 3H‐Rx in a three‐step process from the parent alcohol, resiniferonol (Ro). The tritium label is incorporated into the resiniferonol nucleus at the C20 position, before esterification of 3H‐Ro to 3H‐Rx. This compound will be of use in the elucidation of the binding characteristics of Rx to its biochemical receptor site(s).
Garlic compounds protect vascular endothelial cells from hydrogen peroxide‐induced oxidant injury
Authors: Yamasaki Takeshi , Li Lin , Lau Benjamin H. S.
Published: October 2006

Oxygen radical injury and lipid peroxidation have been suggested as major causes of cancer, atherosclerosis and the aging process. In this study, we determined in vitro the effect of aged garlic extract (AGE) and one of its components, S‐allyl cysteine (SAC), on hydrogen peroxide (H2O2)‐induced oxidant injury using bovine pulmonary artery endothelial cells (PAEC). After overnight preincubation with AGE or SAC, PAEC monolayers were exposed to H2O2 for 3 h. Cell viability, lactate dehydrogenase (LDH) release and lipid peroxidation were measured to assess oxidant injury. Pretreatment with AGE at 2–4 mg/mL or SAC at 4 mg/mL significantly reversed the loss of cell viability induced by 50 and 100 μm of H2O2. AGE or SAC also exhibited a dose‐dependent inhibition of both LDH release and lipid peroxidation induced by 50 μM of H2O2. The results show that both AGE and SAC can protect vascular endothelial cells from oxidant injury. The data thus suggest that these compounds may be useful for retardation of the aging process and for prevention of cancer and atherosclerosis.
Flavonoid treatment reduces glycation and lipid peroxidation in experimental diabetic rats
Authors: Vertommen J. , van den Enden M. , Simoens L. , de Leeuw I.
Published: October 2006

It has been reported that flavonoids in vitro have the capacity to inhibit aldose reductase. The aim of this study was to evaluate this property in vivo. We chose diosmin, a freely available and inexpensive flavonoid without major side effects. Streptozotocin diabetic rats were treated for a period of 8 months with diosmin, mixed with their food. Sorbitol accumulation was measured in erythrocytes and in eye lenses. In these tissues diosmin did not appear to inhibit aldose reductase.

However, diosmin‐treated animals maintained a greater body weight than the untreated group. Although the glycaemic values were the same, and the insulinaemias even lower in the diosmin group, glycated haemoglobin was significantly decreased compared with the untreated animals. Skin collagen fluorescence, an index of collagen glycation, was also significantly decreased in the treated animals. Malondialdehyde, a stable end product of lipid peroxidation, was decreased in the treated animals. Diosmin was well tolerated by the animals.

In conclusion, diosmin is a safe and inexpensive product. It cannot inhibit aldose reductase activity in vivo but diosmin causes a significant reduction of the glycation of proteins in diabetic animals. Inhibition of lipid peroxidation is also observed but it is not clear whether or not this phenomenon is a direct consequence of the decreased glycation.
Pharmacological properties of Visnea mocanera L. f. extracts: Screening for analgesic, antipyretic, antiinflammatory and ulcerogenic activities in rodents
Authors: Hernández‐Pérez M. , Sánchez‐Mateo C. C. , Darias V. , Rabanal R.
Published: October 2006

Different extracts of Visnea mocanera L. f. (Theaceae) were evaluated for analgesic, antipyretic, antiinflammatory and ulcerogenic properties in mice and rats. The acetone extract from the leaves and the syrup from the fruits exerted central analgesic properties, associated with significant but transient antiinflammatory effects on acute inflammatory processes. The acetone extract also possessed topical antiinflammatory effects. The extracts assayed did not display antipyretic and ulcerogenic activity. Sub‐acute toxicological experiments indicated a very low toxicity in mice.
In vitro antiplasmodial effects of diospyrin, a plant‐derived naphthoquinoid, and a novel series of derivatives
Authors: Hazra Banasri , Ghosh Rina , Banerjee Amalendu , Kirby Geoffrey C. , Warhurst David C. , Phillipson J. David
Published: October 2006

Synthesis of derivatives of diospyrin, a natural product, has led to the modification of its tumour‐inhibitory effect, in vitro, towards Ehrlich ascites carcinoma and antiparasitic activity against Leishmania donovani in vitro. The present study shows that two of these novel hydroquinoid analogues derived from diospyrin also show enhanced inhibitory effects against Plasmodium falciparum, in vitro, and may be a useful model for the development of novel antimalarial drugs.
Inhibition of tumour‐promoter‐enhanced 32Pi‐incorporation into cellular phospholipids by flavonols from genus Chrysosplenium
Authors: Arisawa Munehisa , Shimizu Mineo , Satomi Yoshiko , Nishino Atsuko , Nishino Hoyoku , Iwashima Akio
Published: October 2006

Flavonol aglycones from the genus Chrysosplenium showed potential antitumour‐promoter activity. Three flavonols, oxyayanin A and chrysosplenols D and E, markedly inhibited the incorporation of 32Pi into phospholipids of confluent HeLa cells stimulated by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a potent tumour promoter. The potency of the flavonols proved to be similar to those of other antitumour‐promoting flavonoids.
A microbiological evaluation of medicinal plants used by the Maya people of Southern Mexico
Authors: Meckes Mariana , Villarreal Ma. Luisa , Tortoriello Jaime , Berlin Brent , Berlin Eloise Ann
Published: October 2006

A microbiological evaluation was conducted on those medicinal plants most frequently used to treat gastrointestinal and respiratory diseases by Tzeltal and Tzotzil communities in the highlands of Chiapas. The results obtained showed that many of the species induced antimicrobial activity in vitro. The present study allowed selection of three groups of plants with potent effect against gram‐positive Staphylococcus aureus, gram‐negative Escherichia coli bacteria and Candida albicans. It was also demonstrated that 63% of the botanical species that showed antimicrobial properties, enhanced (46%) or induced (17%) the effect under exposure of the plant extracts to UV‐A light. In the search for new molecules with therapeutic value, the present screening offers a preliminary selection of groups of botanical species; within each, there are several representatives that merit further evaluation as potential antibiotics and photosensitizers.
Smooth muscle relaxant activities of compounds isolated from malaysian medicinal plants on rat aorta and guinea‐pig ileum
Authors: Mustafa Mohd. Rais , Mohamad Rohaini , Din Laily , Wahid Shamsuddin
Published: October 2006

Muscle relaxant activities of six compounds isolated from Malaysian medicinal plants were investigated on the smooth muscles of the rat aorta and longitudinal muscle of the guinea‐pig ileum. Except for goniothalamin, the other five compounds exhibited varying degrees of muscle relaxant activities on the two smooth muscles. Dicentrine, isocorydine, altholactone and usnic acid reduced the contractions to KCI and phenylephrine in the rat aorta, whilst atranorin slightly reduced the contractions to phenylephrine but not KCI. In addition, dicentrine and isocorydine markedly reduced the contractile response to phenylephrine in Ca2+‐free Krebs solution. In the longitudinal muscle of the guinea‐pig ileum, altholactone, atranorin, dicentrine and isocorydine inhibited to a greater extent the phasic than the tonic responses to KCI. All four compounds similarly inhibited the contractions induced by ACh. The results suggest that the relaxant activities of the compounds are attributed mainly to inhibition of Ca2+ influx via the calcium channels in the membrane of the smooth muscles. Furthermore, the greater sensitivity of dicentrine, isocorydine and altholactone against phenylephrine‐induced contractions or KCI‐induced phasic contractions are due to their abilities to inhibit intracellular Ca2+ release in these muscles.
General Treatment of Heteroatoms with the Randic Molecular Connectivity Index
Authors: Kupchik Eugene J.
Published: October 2006

Excellent structure‐molar refraction relationships of alkylphosphines, dialkyl sulfides, alkylthiols, alkylamines, dialkyl ethers, and aliphatic alcohols were obtained using the Randic molecular connectivity index. Excellent structure‐molar refraction relations were also obtained using two empirically‐modified connectivity indices which reflect either the difference in bond length between the heteroatom‐carbon bond and a carbon‐carbon bond or the difference in covalent radius between the heteroatom and a carbon atom. Use of the empirically‐modified indices improves the prediction of molar refraction for a mixed set of alkylphosphines, dialkyl sulfides, alkylthiols, alkylamines, dialkyl ethers, aliphatic alcohols, alkanes, alkylsilanes, alkylgermanes, and alkyl halides.
Comparison of Fragment Weighting Schemes for Substructural Analysis
Authors: Ormerod Ann , Willett Peter , Bawden David
Published: October 2006

Several methods have been described in the literature for the calculation of weights which represent the contribution of fragments to the overall activity or inactivity of molecules which contain them. These weighting schemes are based on fragment occurrence data in training sets of molecules for which the activity is known. This paper reports a comparison of several such schemes (fourteen fragment weights in all), using small datasets for which structural and activity data are available. The comparison reveals that the most effective weight seems to be one derived from research into document retrieval systems (where indexing terms are used to discriminate between relevant and non‐relevant documents).
Structure‐Activity Models for Molar Refraction of Alkylsilanes Based on Molecular Connectivity
Authors: Hall Lowell H. , Aaserud David
Published: October 2006

Structure‐activity models are established using molecular connectivity indexes for the molar refraction of 115 alkylsilanes containing 10 monoalkyl‐, 14 dialkyl‐, 32 trialkyl‐and 59 tetraalkylsilanes. In the model based only on 1χ, r = 0.997, s = 1.47, F = 20367. For the two indexes, 1χ and 2χv, r = 0.9987, s = 1.020 and for the three‐variable model based on 0χv, 1χ and 2χv, r = 0.9994, s = 0.664. The quality of these models, based on the Kier‐Hall valence delta formalism, suggests the adequacy of that formalism in encoding the atomic characteristics of silicon in this data set. As a further test of the formalism, a mixed data set of 46 alkylsilanes, 46 alkanes and 41 chloroalkanes was investigated. For the same three indexes, 0χv, 1χ and 2χv, r = 0.9996, s = 0.369. To reduce the intercorrelation between the two low order chi indexes, a linear transformation of these variables is introduced. The sum of a simple and valence index is used in place of the indexes themselves. The quality of the correlations is essentially the same using these sum variables. These results are compared to a proposed empirical modification of the valence delta for alkylsilanes.
Topological Indices in Correlation Analysis. Part 2. Molecular Shape Indices in Modelling of the Chromatographic Retention Parameters
Authors: Mokrosz Jerzy L. , Duszyńska Beata
Published: October 2006

Different chromatographic data sets for hydrocarbons, alcohols, aldehydes, ketones, esters and barbiturates picked up from the literature were correlated with the kappa molecular shape indices. All correlations were statistically highly significant. Application of the kappa indices in such modelling is discussed.
Hydrophobicity Parameter of Diazines (1) Analysis and Prediction of Partition Coefficients of Monosubstituted Diazines
Authors: Yamagami Chisako , Takao Narao , Fujita Toshio
Published: October 2006

The octanol/water partition coefficient (P) of a number of monosubstituted diazines was measured. The composition of the π value of substituents, the increment in the logP value accompanied with the introduction of substituents, was examined in terms of physicochemical substituent parameters and correlation analysis. The diazine‐π value of substituents was generally higher than the pyridine‐π value of corresponding substituents, indicating that the intramolecular electronic interactions between the ring‐N atoms and substituent are more pronounced than those in substituted pyridines in governing the logP value of the molecule. Except for 2‐substituted pyrimidines, the π value of substituents in each series of monosubstituted diazines was in general nicely correlated with the π value of the corresponding substituents in substituted pyridines along with electronic parameter terms representing “bidirectional” electronic effects on the relative solvation of the ring‐N atom(s) and the hydrogen‐bondable substituents with partitioning solvents according to the procedure proposed previously for the analysis of the π value in disubstituted benzenes and monosubstituted pyridines. Keeping in mind that 2‐pyrimidines substituted by hydrogen‐bondable groups sometimes behave as outliers, the correlations were believed to be usable for prediction of logP value of monosubstituted diazines.
A Strategy for Ranking Environmentally Occurring Chemicals. Part IV: Development of Chemical Model Systems for Characterization of Halogenated Aliphatic Hydrocarbons
Authors: Lindgren Fredrik , Eriksson Lennart , Hellberg Sven , Jonsson Jörgen , Sjöström Michael , Wold Svante
Published: October 2006

Eight chemical model systems were developed for a multivariate physicochemical characterization of halogenated aliphatics. The chemical model systems were developed to obtain descriptors which contained information related to lipophilicity and chemical reactivity of the studied compounds. A selected set of 15 halogenated aliphatic compounds were characterized by the chemical model systems. The information content in eight new descriptors combined with eight old physico‐chemical descriptors were validated in a QSAR. The used biological responses were acute oral toxicity to rat, highest non‐lethal dose to mouse and in vitro genotoxicity from a DNA precipitation assay. This model was compared with a QSAR based on eight old‐physico‐chemical descriptors. It was found that the addition of the new descriptors improved the QSAR.
Theoretical Determination of the Putative Receptor‐bound Conformations of 5‐HT2 Receptor Agonists
Authors: Höltje Hans‐Dieter , Briem Hans
Published: October 2006

For a series of compounds with agonistic activity at the 5‐HT2 receptor a pharmacophoric model was established. It has been shown by means of conformational analyses and molecular electrostatic potential calculations that the pharmacophores of all active compounds can adopt common positions at the receptorsite. Besides our model offers an explanation for the stereoselectivity of the chiral compounds as well as for the complete loss of activity of a phenylethylamine compound containing an α,α‐dimethyl sidechain.
Prediction of Mammalian Toxicity by Quantitative Structure Activity Relationships: Aliphatic Amines and Anilines
Authors: Jäckel Hannelore , Klein Werner
Published: October 2006

Quantitative Structure‐Activity Relationships (QSARs) are derived to predict oral toxicity data of aliphatic amines and anilines for rats. LD50‐values from the RTECS data base are correlated to 1‐octanol/water partition coefficient (logPow), fragment‐values and electronic properties. Toxicity data of aliphatic monoamines are sufficiently described by a bilinear logPow‐dependent equation, consideration of polyamines requires a fragment‐descriptor reflecting the polyfunctionality. Toxicity data of anilines are best predicted by a combination of electronic, steric and hydrophobic parameters.

The validity of the developed models is compared with known QSARs.
Single Class Discrimination Using Principal Component Analysis (SCD‐PCA)
Authors: Rose Valerie S. , Wood John , Macfie Halliday J. H.
Published: October 2006

Single Class Discrimination using Principal Component Analysis (SCD‐PCA) has been developed to discriminate an embedded data class. The embedded class is defined as the active class and the diffuse class, or classes as the inactives. Two basic methods are described. Both involve an initial column centring and scaling of the data to the actives space. Method I then directly obtains the directions of maximum variance in the inactives by PCA, while method II attempts to maximize the ratio of inactives to actives variance using PCA. The methods offer good potential to reveal a tightly bedded active class near the origin with the inactives dispersed. Techniques to portray the discrimination power and significance of the PCs are discussed. SCD‐PCA has been applied to artificial data sets exhibiting a variety of distributional characteristics and to two QSAR data sets. The method performed predictably on the artificial data. Good, low dimensional PC models were obtained for the QSAR data sets which were stable when cross‐validated.
A Linear Molecular Similarity Index
Authors: Reynolds Christopher A. , Burt Catherine , Graham Richards W.
Published: October 2006

Molecular similarity is a tool for rationalising the biological activities of potential drug molecules. The most useful form of molecular similarity calculations are usually based upon the molecular electrostatic potential and generally use formulae due to Carbo or Hodgkin but these formulae do not give a similarity index which varies linearly with molecular electrostatic potential. Consequently, a new linear index has been proposed and the potential advantages of this index are discussed.
3D‐Quantitative Structure‐Activity Relationships: Description of Electronic Effects Directly from 3D Structures Using a GRID‐Comparative Molecular Field Analysis (CoMFA) Approach
Authors: Kim Ki Hwan
Published: October 2006

The applicability of the comparative molecular field analysis (CoMFA) method to describe the electronic effects in 3D quantitative structure‐activity relationships (QSAR) has been investigated. Molecular fields calculated using an H + probe with the GRID force fields produced significant correlations with excellent cross‐validations. The CoMFA correlations were compared with the correlations of Hammett σ, σ+ or σ– in the traditional biological QSAR. The results indicate that the CoMFA treatment of electronic effects using an H+ probe as in this study are adequate for describing the corresponding effects in 3D QSAR studies.
Using Theoretical Descriptors in Quantitative Structure‐Activity Relationships: Opiate Receptor Activity by Fentanyl‐like Compounds
Authors: Famini George R. , Ashman William P. , Mickiewicz Alexander P. , Wilson Leland Y.
Published: October 2006

The number of applications of computational techniques to medicinal chemistry is growing rapidly. Quantitative Structure‐Activity Relationships (QSAR) have been used very successfully to correlate structural features to biological activities. A type of QSAR, Linear Solvation Energy Relationships (LSER) has been used to correlate a large number and wide variety of biological properties. Famini and Wilson have developed a theoretical extension of the LSER, called the TLSER, that incorporates only computationally derived descriptors. We have applied the TLSER methodology to a series of fentanyl‐like compounds that exhibit activity at the opiate receptor. TLSER correlations of the entire data set, as well as specific subsets are considered.
Comparison of the Minimal Steric Difference (MTD) and Comparative Molecular Field Analysis (CoMFA) Methods for Analysis of Binding of Steroids to Carrier Proteins
Authors: Oprea Tudor I. , Ciubotariu Dan , Sulea Traian I. , Simon Zeno
Published: October 2006

Cross validation and results with test series indicate similar predictive power for the CoMFA and the much less CPU‐time consuming MTD method. We present an MTD analysis for the binding of a series of 21 steroids to Corticosteroid Binding Globulin (CBG) and to Testosterone Binding Globulin (TeBG) series previously analyzed by CoMFA. For the construction of the hypermolecule we used crystal structures of available steroids retrieved from the Cambridge Crystallographic Data Center (CCDC) and the COSMIC software for structural manipulation and molecular superposition. The correlation results of MTD were r2 = 0.93 for CBG binding and r2 = 0.85 for TeBG binding. The distribution of cavity and wall vertices of the MTD receptor maps present some similarities with the CoMFA coefficient contour maps. Cross validation results of MTD (50% of data in one subseries and 50% in the second), with r2 = 0.70 for CBG and r2 = 0.72 for TeBG binding, are somewhat better than CoMFA results, r2 = 0.66 and r2 = 0.555 respectively, while CoMFA predictions for a separate series of 10 steroids are better. In CoMFA, the equation derived for the molecule receptor affinity corresponds to molecules which interact with “receptor” atoms in fixed positions by electrostatic and van der Waals 6–12 potentials. Repulsions are thereby very high for some of the van der Waals terms – while in reality the overlapping of the ligand and receptor van der Waals envelopes are circumvented by conformational transitions at lower energy costs. This may explain why the elegant CoMFA method indicates only receptor regions whose occupation by the ligand molecules have a favorable or unfavorable effect upon binding.
Modelling the Ionization Potential of Halogenated Aliphatics
Authors: Chiorboli Claudio , Piazza Rossano , Carassiti Vittorio , Passerini Laura , Tosato Maria Livia
Published: October 2006

A multivariate QSAR for estimating the ionization potential (IP) of halo‐alkanes has been constructed. 69 compounds, including 47 for which experimental IP data in the 10 to 13.6 eV were available were parametrized with 12 structural descriptors. The data analysis to correlate IP to these descriptors was carried out by PLS that gave a tri‐dimensional model explaining over 80% of the variance of IP. The reliability of the model was evaluated on the basis of predictions by using two different approaches. These were (a) a modified PLS version providing the Standard Deviation of Errors of Prediction, the SDEP parameter, which was found to be +/− 0.45 eV, and (b) an “external” validation process where the standard deviation was computed on the basis of the predicted IP.s for 17 compounds kept outside the training set, and was found to be +/− 0.39 eV.