Specific responses of monoamine neurotransmitters to various acute stressors

This study determined the composition of histamine,serotonin and dopamine using high performance liquid chromatography and electrochemical detection,and compared the changes in monoamine levels in plasma,the cortex and midbrain of mice exposed to acute stressors,such as blood-drawing stimulation or restraint.Results demonstrated that plasma histamine levels were markedly increased when mice were exposed to blood-drawing stimulation and restraint stress.However,serotonin levels decreased in plasma of mice treated with restraint stress,and dopamine levels in plasma had no significant response to the two acute stressors.The three monoamines （histamine,serotonin and dopamine） increased at different degrees in restraint mice,but not in brain regions of blood-drawing stressed mice.Results indicated that histaminergic,serotonergic or dopaminergic systems have their own specific response to different acute stressors.

Microbial transformation for Region-selective Hydroxylation of Z-Butylidenephthalide by Aspergillus niger CGMCC 3.739

Microbial transformation is a useful tool for structure modification of active natural products.Z-Butylidenephthalide is the main active constituent of Angelica sinensis.In the present work,a pair of new oxidized metabolites,namely(-)(11R)-(Z)-11-hydroxy-butylidenephthalide(1a)and(+)(11S)-(Z)-11-hydroxy-butylidenephthalide(1b),were obtained from microbial transformation for region-selective 11-hydroxylation of Z-butylidenephthalide by Aspergillus niger CGMCC 3.739.Their structures,including absolute configurations,were elucidated by extensive analysis of HR-ESI-MS,NMR spectra,and the modified Mosher’s method.This is the first study on the microbial transformation of Z-butylidenephthalide,and these findings offer a tool for region-selective 11-hydroxylation of Z-butylidenephthalide.

Targeted isolation of antiviral cinnamoylphloroglucinol-terpene adducts from Cleistocalyx operculatus by building blocks-based molecular networking approach

The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene adducts(CPTAs)with diverse skeleton types(cleistoperones A-R,1-18).Their structures including absolute configurations were determined by extensive spectroscopic methods,quantum chemical calculations,and single-crystal X-ray crystallographic experiments.Cleistoperone A(1),consisting of a cinnamoylphloroglucinol motif and two linear monoterpene moieties,represents an unprecedented macrocyclic CPTA,whose densely functionalized tricyclo[15.3.1.0^(3,8)]heneicosane bridge ring skeleton contains an enolizableβ,β′-triketone system and two different kinds of stereogenic elements(including five point and three planar chiralities).Cleistoperones B and C(2 and 3)are two new skeletal CPTAs with an unusual coupling pattern between the(nor)monoterpene moiety and the cinnamoyl chain of the cinnamoylphloroglucinol unit.Cleistoperone D(4)possesses an unprecedented cage-like 6/6/6/4/6-fused heteropentacyclic scaffold.The plausible biosynthetic pathways for 1-18 were also proposed.Notably,compounds 1,4,7,8,and 18 exhibited significant antiviral activity against respiratory syncytial virus(RSV).The most potent one,cleistoperone A(1)with IC_(50) value of 1.71±0.61μmol/L,could effectively inhibit virus replication via affecting the Akt/mTOR/p70S6K signaling pathway.

High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding Xue Bi Jing, a five-herb medicine, to antibioticbased sepsis care. Although adding Xue Bi Jing further reduced 28-day mortality via modulating the host response, pharmacokinetic herbedrug interaction is a widely recognized issue that needs to be studied.Building on our earlier systematic chemical and human pharmacokinetic investigations of Xue Bi Jing, we evaluated the degree of pharmacokinetic compatibility for Xue Bi Jing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both Xue Bi Jing-antibiotic and antibiotic-Xue Bi Jing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study Xue Bi Jing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no Xue Bi Jing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could,due to their inhibition of uridine 50-diphosphoglucuronosyltransferase 2 B15, organic anion transporters1/2 and/or organic anion-transporting polypeptide 1 B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions(resulting in increased exposure) are likely desirable due to these Xue Bi Jing compounds’ low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from Xue Bi Jing.Collectively, Xue Bi Jing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

接种发酵和自然发酵中酿酒酵母菌株多样性比较

【目的】探究自然发酵和接种发酵两种发酵方式,对霞多丽葡萄发酵中酵母菌种多样性和酿酒酵母菌株遗传多样性的影响。【方法】以霞多丽葡萄为原料,分别进行自然发酵和接种不同酿酒酵母菌株(NXU17-26、UCD522和UCD2610)的发酵,利用26S rDNA D1/D2区序列分析和Interdelta指纹图谱技术分别进行酵母菌的种间及种内水平的区分,通过聚类分析及多样性指数对不同发酵方式下酿酒酵母菌株的多样性进行分析和比较。【结果】自然发酵的发酵曲线较平缓,接种发酵的发酵速度显著快于自然发酵。26S rDNA D1/D2区序列分析将4个发酵中分离到的酵母菌鉴定为6属11种,自然发酵中分离的酵母有5属6种,均为非酿酒酵母(non-Saccharomyces);而接种发酵中的酵母多样性远低于自然发酵,均由酿酒酵母和两种非酿酒酵母组成。Interdelta指纹图谱分析表明,接种UCD2610的发酵中,发酵后UCD2610是优势菌株,其基因型占比为48.78%;接种NXU17-26和UCD522的发酵中,未发现与NXU17-26和UCD522相同的基因型。聚类分析表明,分离自接种UCD522发酵中的酿酒酵母菌株间的遗传差异性较小;而分离自NXU17-26和UCD2610发酵中的酿酒酵母菌株间遗传差异性较大。多样性指数结果表明,接种UCD2610发酵中的优势菌株(UCD2610)在发酵过程中占据更加突出的地位;接种UCD522发酵中分离的酿酒酵母具有更高的多样性,影响其菌株多样性的未知因素较多,且不同基因型酿酒酵母的集中度较高。【结论】发酵方式对霞多丽葡萄发酵中酵母菌种多样性、以及酿酒酵母菌株遗传多样性的影响显著,研究结果对葡萄酒发酵中的微生物控制具有指导意义。

Tripodalsporormielones A-C,unprecedented cage-like polyketides with complex polyvdent bridged and fused ring systems

A chemical investigation on Sporormiella sp.led to the isolation and structural elucidation of tripodalsporormielones Ae C(1-3),a new class of polyketide possessing unprecedented cage-like skeletons with polyvdent bridged and fused ring systems.These polyketides with cage-like skeletons were characterized as a high non-protonated carbon-containing system,which resulted in few HMBC correlations observed and made the accurate structures hard to be obtained by NMR.Especially,some signals of non-protonated sp;carbons are weak and even unobservable in compound 1.In order to establish the structure of 1,the calculated NMR with DP4 evaluation was applied to determine the structure from the plausible structure candidates obtained from the detailed NMR analysis.Based on NMR experiments and calculated NMR,the structures of isolated compounds were established and confirmed by X-ray technology.Through chiral isolation,the optically pure enantiomers of 1 and 3 were obtained,and their absolute configurations were determined based on ECD quantum chemical calculation.Based on the isolated compounds and our previous work,1-3 would be derived from 3-methylorcinaldehyde,and their plausible biosynthetic mechanism was proposed.Furthermore,1 exhibited obvious short-term memory improvement activity on an Alzheimer’s disease fly model.