Juliflorine: A potent natural peripheral anionic-site-binding inhibitor of acetylcholinesterase with calcium-channel blocking potential, a leading candidate for Alzheimer’s disease therapy

The alkaloid juliflorine (1) from Prosopis juliflora inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC₅₀ values 0.42 and 0.12 μM, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that the nature of inhibition was purely of non-competitive type with K_i values 0.4 and 0.1 μM, against AChE and BChE, respectively. By molecular docking studies compound 1 was found to be ideally spaced inside the aromatic gorge of AChE with rings A/B remaining at the top and rings C/D penetrating deep into the gorge, that might be due to the greater hydrophobicity of rings C/D as compared to rings A/B, allowing their simultaneous interaction with the peripheral anionic and quaternary ammonium-binding sites. The 1-AChE complex was found to be stabilized by hydrophobic contacts, hydrogen bonding, and π-π stacking between the compound 1 and amino acid residues of the aromatic gorge of AChE. Amino acid residues Tyr70, Asp72, Tyr121, Trp279, and Tyr334 of the peripheral anionic site (PAS) of AChE were found to be exclusively involved in the hydrophobic contacts with compound 1 that might be responsible for the competitive mode of inhibition. Compound 1 also showed dose-dependent (30-500 μg/mL) spasmolytic and Ca²⁺-channel blocking activities in isolated rabbit jejunum preparations. The cholinesterase inhibitory potential along with calcium-channel blocking activity of compound 1 and safe profile in human neutrophils viable assay could make it a possible drug candidate for Alzheimer’s disease.     

The Deuterator: software for the determination of backbone amide deuterium levels from H/D exchange MS data

Background  

The combination of mass spectrometry and solution phase amide hydrogen/deuterium exchange (H/D exchange) experiments is an effective method for characterizing protein dynamics, and protein-protein or protein-ligand interactions. Despite methodological advancements and improvements in instrumentation and automation, data analysis and display remains a tedious process. The factors that contribute to this bottleneck are the large number of data points produced in a typical experiment, each requiring manual curation and validation, and then calculation of the level of backbone amide exchange. Tools have become available that address some of these issues, but lack sufficient integration, functionality, and accessibility required to address the needs of the H/D exchange community. To date there is no software for the analysis of H/D exchange data that comprehensively addresses these issues.     

豆科黄结属模式及其相关种名的考证

长期以来,Ｔermopsis lanceolata R.Br.被误认为是黄华属的模式。根据有关文献考证和国际植物命名法规,作者为认Ｔ.;lanceoltata是一个不合法名,黄华属的合法模式应为Ｔhermopsis Lupinoides(L.)Link.分布于东北亚,花具互生花的黄华长期被误定为Ｔ。lupinoides(L.)Link,应更正为Ｔhermopsis fabacea(Pall)DC.。     

Enzyme inhibition and radical scavenging activities of aerial parts of Paeonia emodi Wall. (Paeoniaceae)

The ethanolic extract derived from aerial parts of an indigenous medicinal plant Paeonia emodi was screened for enzyme inhibition activities against Urease (jack bean and Bacillus pasteurii) and α-Chymotrypsin. The extract was also investigated for its radical scavenging activity using DPPH assay. The crude extract was found to possess significant enzyme inhibition activities against jack bean (74%) and Bacillus pasteurii (80%) urease and a moderate activity (54%) against α-Chymotrypsin. The extract also displayed excellent (83%) radical scavenging activity. On the basis of these results, the crude extract was subsequently fractionated into n-hexane, chloroform, ethyl acetate, n-butanol and water fractions and tested independently for the aforesaid activities. Significant inhibitory activity against urease enzyme was observed for the ethyl acetate, n-butanol and water fractions while the n-hexane and chloroform fractions were devoid of any such activity. In the α-Chymotrypsin enzyme inhibition studies the activity was concentrated into the ethyl acetate fraction. All the fractions displayed potent radical scavenging activity. The crude extract and fractions thereof were also subjected to total phenolic content determination. A correlation between radical scavenging capacities of extracts and total phenolic content was observed in the majority of cases.     

Determination of antimicrobial and phytochemical compounds of Jatropha curcas plant

The aim of this study was to explore the effectiveness of different parts of J. curcas plant against some selected human pathogens as antimicrobial agent which are known to cause diseases and to check antioxidant and phytochemicals from different plant sections of J. curcas. Plant extracts were analyzed by quantification of antimicrobial and phytochemical compounds. This study reveals that 20% ethanol stem extract of J. curcas showed maximum antibacterial activity (40 ± 0.0 mm) against Klebsiella pneumonia. Water extract of root of J. curcas also inhibited E. coli (35.25 ± 0.35 mm). The growth of K. pneumonia and Agrobacterium tumifaciens were also ceased when ethanol extract of J. curcas root applied to check their potential as antimicrobial agent. The results also revealed that fungal species, Aspergillus niger, and Pencillium notatum noted the maximum antifungal activity in ethanol extract of flower and methanol extract of root (38.5 ± 0.7 mm) and (27.25 ± 0.35 mm) respectively. Phytochemicals and many secondary metabolites were present in J. curcas extracts such as alkaloids, steroids, tannins, glycosides, flavonoids, saponins, courmerin, and phenolic compounds. It also showed the highest density of color in the different parts of plant extract of J. curcas. Similarly, biochemical primary metabolites were observed at maximum amount of biochemical in different parts of J. curcas, and correlated with antimicrobial activity. The study concluded that J. curcas has great potential as antibacterial agent and cure various human pathogens.     

秦渭玫瑰精油研究

采用ISO9842和GB11538-89对在陕西渭南栽培的大马士革玫瑰“卡赞勒克”精油(工业化蒸馏法提取产品)进行了分析,结果表明,精油产品各项指标均符合ISO 9842和保加利亚БДС653标准要求。证明引种国际香型(纯甜型)玫瑰品种在陕西渭南栽培是成功的,所用精油提取工艺是合理的。