Uncarialins J-M from Uncaria rhynchophylla and Their Anti-depression Mechanism in Unpredictable Chronic Mild Stress-Induced Mice via Activating 5-HT_(1A) Receptor

Uncaria rhynchophylla has been widely used to treat central nervous system diseases for a long history.After investigation of U.rhynchophylla,eleven monoterpene indole alkaloids,including four new compounds uncarialins J-M(1-4)and seven known analogues(5-11),were isolated and identified.Their structural characterization was conducted using HRESIMS,1D and 2D NMR,electronic circular dichroism(ECD)spectra,and quantum chemical computations.Compounds 1,2,7,and 9-11 displayed significant ag-onistic effects towards 5-HT_(1A) receptor,and their EC_(50) values were 7.86,732,2.24,1.18,1.52,and 3.75μmol/L,respectively.Furthermore,in vivo experimental results fully revealed that hirsuteine(7)displayed a significant antidepression effect in unpredictable chronic mild stress(UCMS)-induced depression mice mainly via regulating 5-HT_(1A) signaling pathway.Molecular docking and site-directed amino acid mutation verified that amino acid residues Aspll6 and Asn386 were the binding sites of hirsuteine(7)with 5-HT_(1A) receptor.In addition,pre-treatment of mice with WAY 100635 also blocked the anti-depression effect of hirsuteine(7),which further demonstrated that 5-HT_(1A) receptor was a potential target of hirsuteine(7)to effectively treat depression.These findings indicated the therapeutic material basis of U.rhynchophylla and the anti-depression underlying mechanism of hirsuteine(7),and further provided the useful guidance for the development of hirsuteine(7)as a potential antidepressant candidate.

Analysis of human infectious avian influenza virus:Hemagglutinin genetic characteristics in Asia and Africa from 2004 to 2009

In the present study,we used nucleotide and protein sequences of avian influenza virus H5N1,which were obtained in Asia and Africa,analyzed HA proteins using ClustalX1.83 and MEGA4.0,and built a genetic evolutionary tree of HA nucleotides.The analysis revealed that the receptor specificity amino acid of A/HK/213/2003,A/Turkey/65596/2006 and etc mutated into QNG,which could bind withá-2,3 galactose andá-2,6 galactose.A mutation might thus take place and lead to an outbreak of human infections of avian influenza virus.The mutations of HA protein amino acids from 2004 to 2009 coincided with human infections provided by the World Health Organization,indicating a“low–high–highest–high–low”pattern.We also found out that virus strains in Asia are from different origins:strains from Southeast Asia and East Asia are of the same origin,whereas those from West Asia,South Asia and Africa descend from one ancestor.The composition of the phylogenetic tree and mutations of key site amino acids in HA proteins reflected the fact that the majority of strains are regional and long term,and virus diffusions exist between China,Laos,Malaysia,Indonesia,Azerbaijan,Turkey and Iraq.We would advise that pertinent vaccines be developed and due attention be paid to the spread of viruses between neighboring countries and the dangers of virus mutation and evolution.