Partitioning the variation within the acid neutralizing capacity of surface waters in Scotland in relation to land cover, soil and atmospheric depositional factors.

A method of decomposing the variation in the acid neutralizing capacity (ANC) of surface waters in Scotland is described. Using national datasets, a series of variables relating to 703 catchments across Scotland is divided into three components representing (i) land cover, (ii) soil and (iii) atmospheric deposition/altitude. Redundancy analysis (RDA) and (partial) redundancy analysis are used to quantify the amount of variation in ANC uniquely attributable to each of these components, independent of the effects of the others. The variation accounted for by covarying combinations of these components is also determined. Approximately 55% of the total variation in ANC across the 703 sites is explained by the variables representing catchment characteristics and atmospheric deposition. Of this, 8.5%, 2.4% and 6.9% are uniquely attributable to the land cover, soil and deposition/altitude components, respectively. A further 38% of ANC variation is associated with the covariation between components, with 18% accounted for by the combination of all three. Approximately 45% of the variation in ANC remains unexplained. The results reflect the integrated nature of catchment processes and demonstrate, for these data, that it is a combination of land cover, soil and deposition and altitude factors which most explain variation in freshwater ANC level. The approach offers a tool with which to assess the sensitivity of surface waters to acid deposition at a regional scale and provides a way of identifying regional differences in catchment response to acid loading.

Interaction of nitrogen deposition and land use on soil and water quality in Scotland: issues of spatial variability and scale.

Over large areas of the Scottish uplands anthropogenic sulfur (S) deposition is declining in response to stringent national and European controls on S emissions. At the same time, however, the relative contribution of nitrogenous (N) compounds to the total anthropogenic deposition loading has increased. To investigate the significance of N deposition on the potential acidification of surface waters, national, regional, and catchment databases were developed to assess the relationships between N deposition, soil C/N ratios, land use and surface water NO3 concentrations. National classification schemes for land use and soils were used as only limited empirical data are available at such large spatial scales. Data were screened to eliminate areas where N inputs are dominated by non-atmospheric sources. From these screened datasets, it was apparent that areas with the highest risk of N leaching were situated predominantly in the upland areas of south-west and west Scotland (areas with low soil C/N ratios). At the regional scale, surface-water NO3 concentration in afforested catchments was negatively correlated with soil C/N ratios below 20. This relationship was not evident in moorland catchments, where NO3 leaching was strongly related to N deposition and the loch/catchment ratio, rather than the soil C/N ratio. Temporal trends of regional water quality highlighted as increasing loch NO3 concentrations between 1988 and 1996-1997, presumably reflecting an increase in N deposition, enhanced leaching losses from the terrestrial component of the catchment, or altered in-lake processes. The hydrochemical records for two catchments in NE Scotland (Lochnagar and Allt a Mharcaidh) highlight the importance of within catchment process in controlling the nitrogen response observed in surface waters. The potential mechanisms through which vegetation and soils may modify incoming deposition are discussed.

New iridoids from the medicinal plant Barleria prionitis with potent activity against respiratory syncytial virus.

Two new iridoid glycosides (1 and 2), together with the known compounds barlerin (3) and verbascoside (4), were isolated from Barleria prionitis. The new iridoid glycosides were determined to be 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (1) and its cis isomer (2) by using spectroscopic, especially 2D NMR, data. A 3:1 mixture of 1 and 2 was shown to have potent in vitro activity against respiratory syncytial virus (EC50 2.46 microgram/mL, IC50 42.2 microgram/mL).

Antiviral phenylpropanoid glycosides from the medicinal plant Markhamia lutea.

Three new phenylpropanoid glycosides, named luteoside A (3), luteoside B (4), and luteoside C (5), were isolated together with the known compounds verbascoside (1) and isoverbascoside (2) from the roots of the medicinal plant Markhamia lutea. The structures of the new compounds were determined to be 1-O-(3, 4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-4-O- caffeo yl-6-acetyl-beta-d-glucopyranoside, 1-O-(3,4-dihydroxyphenyl)ethyl beta-d-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- caffeo yl-beta-d-glucopyranoside, and 1-O-(3,4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- ferulo yl-beta-d-glucopyranoside, respectively, on the basis of chemical and spectroscopic data. All five phenylpropanoid glycosides exhibited potent in vitro activity against respiratory syncytial virus.

Two new lignans with activity against influenza virus from the medicinal plant Rhinacanthus nasutus.

Two new lignans, rhinacanthin E (1) and rhinacanthin F (2), were isolated from the aerial parts of the plant Rhinacanthus nasutus. Their structures were established by detailed spectroscopic analysis. These compounds show significant antiviral activity against influenza virus type A.

Cell culture assay system for the evaluation of natural product-mediated anti-Hepatitis B virus activity.

Utilizing the hepatitis B virus (HBV)-producing hepatoblastoma cell line, HepG2.2.15, which is stably transfected with the cloned HBV genome, methods were devised to examine the effects of test substances on intracellular extrachromosomal HBV DNA levels and secretion of hepatitis B surface antigen (HBsAg). The known inhibitor of HBV replication, dideoxycytosine (ddC), had a minor effect on the secretion of HBsAg, but >90% of intracellular extrachromosomal HBV DNA expression was lost at a non-cytotoxic drug concentration (25µM). This inhibitory effect was reversed when ddC was removed from the medium. Of 19 plant materials tested, extracts from the aerial parts of Clematis sinensis Lour, and Clerodendron inerme R. Br. significantly inhibited the secretion of HBsAg into the culture medium at non-cytotoxic concentrations, but had no effect on intracellular extrachromosomal HBV DNA levels. This system is useful for the evaluation of test materials, or combinations of test materials, for their potential to inhibit HBV markers.

SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A) and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses. The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent.

New cytotoxic scalarane sesterterpenes from the Dictyoceratid sponge Strepsichordaia lendenfeldi.

Nine sesterterpenes 1-9 have been isolated from a Dictyoceratid sponge, Strepsichordaia lendenfeldi, collected on the Great Barrier Reef, Australia. Seven of these compounds are new, one [4] had been reported previously as a semisynthetic product, and one [5] had been isolated previously from Carteriospongia foliascens. Unambiguous 13C- and 1H-nmr assignments have been made for 1 based on extensive 1D and 2D high field nmr experiments, which enabled 13C-nmr assignments to be made for 2-9. Significant growth inhibitory effects with tested cancer cell lines are reported for compounds 1-8.

Manoalide: structure-activity studies and definition of the pharmacophore for phospholipase A2 inactivation.

Manoalide is a potent antiinflammatory marine natural product and a direct inactivator of venom phospholipase A2 (PLA2; EC 3.1.1.4). Manoalide has been shown to irreversibly inhibit PLA2, with the corresponding modification of a selective number of lysine residues. The mechanism of inactivation has not yet been elucidated and structure-activity relationship studies were, therefore, performed in order to determine the contributions of the various functional groups incorporated in the gamma-hydroxybutenolide, alpha-hydroxydihydropyran, and trimethylcyclohexenyl ring systems to the efficacy (irreversibility) and potency of this series of inhibitors. These studies indicate that 1) the presence of the hemiacetal in the alpha-hydroxydihydropyran ring is required for irreversible binding of manoalide, 2) the gamma-hydroxybutenolide ring is involved in the initial interaction of manoalide with PLA2, and 3) the hydrophobic nature of the trimethylcyclohexenyl ring system allows nonbonded interactions between manoalide and PLA2 that enhance the potency of these analogs. These structure-activity relationship studies suggest that the closed ring form of manoalide is the predominant molecular species that accounts for the selective and potent inhibition of PLA2 by manoalide. Elucidation of the mechanism awaits further detailed physicochemical studies on the structure of the manoalide (analog)-protein adducts in model systems and using PLA2.

Luffolide, a novel anti-inflammatory terpene from the sponge Luffariella sp..

Luffolide (4) is a minor metabolite of the sponge Luffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products 5 and 6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A2.