Residues and contaminants in medicinal herbs—A review

With the increasing popularity and use of medicinal herbs, their global demand has gained momentum. Developing countries, including China, India and South East Asian (SEA) countries, are the centres of origin and major global suppliers for most of these traditionally used medicinal herbs. One of the factors affecting the quality of these herbs is the contamination of heavy metals, mycotoxins, pesticide residues, polycyclic aromatic hydrocarbons (PAHs) and fumigants. These contaminants can accumulate during the cultivation, storage and processing of herbs and may have adverse effects on consumer health. There have been various reports regarding the presence of these contaminants in medicinal herbs. This review discusses the important contaminants of medicinal herbs, the frequency and magnitude of their occurrences, the potential causes of contamination and their regulatory limits in medicinal herbs. The major challenge in the international trade of medicinal herbs is the lack of common guidelines, regulatory measures and monitoring body to strictly enforce their regulation.     

Catalysis by dienelactone hydrolase: A variation on the protease mechanism

Dienelactone hydrolase (DLH), an enzyme from the β-ketoadipate pathway, catalyzes the hydrolysis of dienelactone to maleylacetate. Our inhibitor binding studies suggest that its substrate, dienelactone, is held in the active site by hydrophobic interactions around the lactone ring and by the ion pairs between its carboxylate and Arg-81 and Arg-206. Like the cysteine/serine proteases, DLH has a catalytic triad (Cys-123, His-202, Asp-171) and its mechanism probably involves the formation of covalently bound acyl intermediate via a tetrahedral intermediate. Unlike the proteases, DLH seems to protonate the incipient leaving group only after the collapse of the first tetrahedral intermediate, rendering DLH incapable of hydrolyzing amide analogues of its ester substrate. In addition, the triad His probably does not protonate the leaving group (enolate) or deprotonate the water for deacylation; rather, the enolate anion abstracts a proton from water and, in doing so, supplies the hydroxyl for deacylation. © 1993 Wiley-Liss, Inc.     

Thiosulfinate Tolerance Is a Virulence Strategy of an Atypical Bacterial Pathogen of Onion

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Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based inhibition

Small molecule inhibitors have a powerful blocking action on viral polymerases. The bioavailability of the inhibitor, nevertheless, often raise a significant selectivity constraint and may substantially limit the efficacy of therapy. Phosphonoacetic acid has long been known to possess a restricted potential to block DNA biosynthesis. In order to achieve a better affinity, this compound has been linked with natural nucleotide at different positions. The structural context of the resulted conjugates has been found to be crucial for the acquisition by DNA polymerases. We show that nucleobase-conjugated phosphonoacetic acid is being accepted, but this alters the processivity of DNA polymerases. The data presented here not only provide a mechanistic rationale for a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted nucleotide functionalization as a route for enhancing the specificity of small molecule inhibitors.     

Understanding Performance Degradation in Cation‐Disordered Rock‐Salt Oxide Cathodes

The collective redox activities of transition‐metal (TM) cations and oxygen anions have been shown to increase charge storage capacity in both Li‐rich layered and cation‐disordered rock‐salt cathodes. Repeated cycling involving anionic redox is known to trigger TM migration and phase transformation in layered Li‐ and Mn‐rich (LMR) oxides, however, detailed mechanistic understanding on the recently discovered Li‐rich rock‐salt cathodes is largely missing. The present study systematically investigates the effect of oxygen redox on a Li_1.3Nb_0.3Mn_0.4O₂ cathode and demonstrates that performance deterioration is directly correlated to the extent of oxygen redox. It is shown that voltage fade and hysteresis begin only after initiating anionic redox at high voltages, which grows progressively with either deeper oxidation of oxygen at higher potential or extended cycling. In contrast to what is reported on layered LMR oxides, extensive TM reduction is observed but phase transition is not detected in the cycled oxide. A densification/degradation mechanism is proposed accordingly which elucidates how a unique combination of extensive chemical reduction of TM and reduced quality of the Li percolation network in cation‐disordered rock‐salts can lead to performance degradation in these newer cathodes with 3D Li migration pathways. Design strategies to achieve balanced capacity and stability are also discussed.     

Mercury contamination and stable isotopes reveal variability in foraging ecology of generalist California gulls

Environmental contaminants are a concern for animal health, but contaminant exposure can also be used as a tracer of foraging ecology. In particular, mercury (Hg) concentrations are highly variable among aquatic and terrestrial food webs as a result of habitat- and site-specific biogeochemical processes that produce the bioaccumulative form, methylmercury (MeHg). We used stable isotopes and total Hg (THg) concentrations of a generalist consumer, the California gull (Larus californicus), to examine foraging ecology and illustrate the utility of using Hg contamination as an ecological tracer under certain conditions. We identified four main foraging clusters of gulls during pre-breeding and breeding, using a traditional approach based on light stable isotopes. The foraging cluster with the highest δ¹⁵N and δ³⁴S values in gulls (cluster 4) had mean blood THg concentrations 614% (pre-breeding) and 250% (breeding) higher than gulls with the lowest isotope values (cluster 1). Using a traditional approach of stable-isotope mixing models, we showed that breeding birds with a higher proportion of garbage in their diet (cluster 2: 63–82% garbage) corresponded to lower THg concentrations and lower δ¹⁵N and δ³⁴S values. In contrast, gull clusters with higher THg concentrations, which were more enriched in ¹⁵N and ³⁴S isotopes, consumed a higher proportion of more natural, estuarine prey. δ³⁴S values, which change markedly across the terrestrial to marine habitat gradient, were positively correlated with blood THg concentrations in gulls. The linkage we observed between stable isotopes and THg concentrations suggests that Hg contamination can be used as an additional tool for understanding animal foraging across coastal habitat gradients.     

Heavy metal pollution in surface water and sediment: A preliminary assessment of an urban river in a developing country

The concentration and chemical fractionation of globally alarming six heavy metals (Cr, Ni, Cu, As, Cd and Pb) were measured in surface water and sediment of an urban river in Bangladesh. The decreasing trend of metals were observed in water as Cr > Cu > As > Ni > Pb > Cd and in sediment as Cr > Ni > Cu > Pb > As > Cd. The level of studied metals exceeded the safe limits of drinking water, indicated that water from this river is not safe for drinking and/or cooking purposes. However, the investigated metals showed low mobility except for Cd and Pb which could pose a severe threat to the aquatic environment. Contamination factor (CF) and geoaccumulation index (I_geo) demonstrated that most of the sediment samples were moderately to heavily contaminated by Cr, As, Cd and Pb. The pollution load index (PLI) values were above one (>1) indicates progressive deterioration of the sediment quality. The extent of pollution by heavy metals in the river Korotoa implies that the condition is much frightening to the biota and inhabitants in the vicinity of the river as well.     

The MDM2 RING Domain and Central Acidic Domain Play Distinct Roles in MDM2 Protein Homodimerization and MDM2-MDMX Protein Heterodimerization

The oncoprotein murine double minute 2 (MDM2) is an E3 ligase that plays a prominent role in p53 suppression by promoting its polyubiquitination and proteasomal degradation. In its active form, MDM2 forms homodimers as well as heterodimers with the homologous protein murine double minute 4 (MDMX), both of which are thought to occur through their respective C-terminal RING (really interesting new gene) domains. In this study, using multiple MDM2 mutants, we show evidence suggesting that MDM2 homo- and heterodimerization occur through distinct mechanisms because MDM2 RING domain mutations that inhibit MDM2 interaction with MDMX do not affect MDM2 interaction with WT MDM2. Intriguingly, deletion of a portion of the MDM2 central acidic domain selectively inhibits interaction with MDM2 while leaving intact the ability of MDM2 to interact with MDMX and to ubiquitinate p53. Further analysis of an MDM2 C-terminal deletion mutant reveals that the C-terminal residues of MDM2 are required for both MDM2 and MDMX interaction. Collectively, our results suggest a model in which MDM2-MDMX heterodimerization requires the extreme C terminus and proper RING domain structure of MDM2, whereas MDM2 homodimerization requires the extreme C terminus and the central acidic domain of MDM2, suggesting that MDM2 homo- and heterodimers utilize distinct MDM2 domains. Our study is the first to report mutations capable of separating MDM2 homo- and heterodimerization.