A new benzylisoquinoline alkaloid from stems of Nelumbo nucifera

新 benzylisoquinoline 碱，命名 nelumstemine (1 ) ， 1-(4 ′ - hydroxybenzoyl )-6,7-dimethoxy-3,4-dihydroisoquinoline, 从 Nelumbo nucifera Geartn 的茎被孤立。它的结构根据光谱分析被建立。

Two new homoisoflavanones from Polygonatum odoratum (Mill.) Druce

Two new homoisoflavanones were isolated from the rhizomes of Polygonatum odoratum (Mill.) Druce and their structures were elucidated as (3R)-5,7-dihydroxy-8-methoxy-3-(4-methoxybenzyl)-6-methylchrom-an-4-one (1) and (3R)-5,7,8-trihydroxy-3-(4-hydroxybenzyl)-6-methylchroman-4-one (2), on the basis of spectral analysis.

Identification and determination of the major constituents in traditional Chinese medicine Longdan Xiegan Pill by HPLC-DAD-ESI-MS

A novel and sensitive HPLC-UV method has been developed for the simultaneous determination of twelve major compounds in Longdan Xiegan Pill.The chemical profile of the twelve compounds,including geniposidic acid(1),geniposide(2),gentiopicroside(3),liquiritin(4),crocin(5),baicalin(6),wogonoside(7),baicalein(8),glycyrrhizic acid(9),wogonin(10),oroxylin A(11)and aristolochic acid A(12),was acquired using high-performance liquid chromatography-diode array detector coupled with an electrospray tandem mass spectrometer(HPLC-DAD-ESI-MS).The analysis was performed on a Dikma Platisil ODS C18 column(250 mm×4.6 mm,5 μm)with a gradient solvent system of acetonitrile-0.1% aqueous formic acid.The validation was carried out and the linearities(r>0.9996),repeatability(RSD<1.8%),intra-and inter-day precision(RSD<1.3%),and recoveries(ranging from 96.6% to 103.4%)were acceptable.The limits of detection(LOD)of these compounds ranged from 0.29 to 4.17 ng.Aristolochic acid A,which is the toxic ingredient,was not detected in all the batches of Longdan Xiegan Pill.Furthermore,hierarchical cluster analysis was used to evaluate the variation of the herbal prescription.The proposed method is simple,effective and suitable for the quality control of this traditional Chinese medicine(TCM).

Screening potential mitochondria-targeting compounds from traditional Chinese medicines using a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method

Mitochondria regulate numerous crucial cell processes, including energy production, apoptotic cell death, oxidative stress, calcium homeostasis and lipid metabolism. Here, we applied an efficient mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry(LC/MS) method,also known as screening method for mitochondria-targeted bioactive constituents(SM-MBC). This method allowed searching natural mitochondria-targeting compounds from traditional Chinese medicines(TCMs), including Puerariae Radix(PR) and Chuanxiong Radix(CR). A total of 23 active compounds were successfully discovered from the two TCMs extracts. Among these 23 hit compounds, 17 were identified by LC/MS, 12 of which were novel mitochondria-targeting compounds. Among these, 6 active compounds were analyzed in vitro for pharmacological tests and found able to affect mitochondrial functions. We also investigated the effects of the hit compounds on Hep G2 cell proliferation and on loss of cardiomyocyte viability induced by hypoxia/reoxygenation injury. The results obtained are useful for in-depth understanding of mechanisms underlying TCMs therapeutic effects at mitochondria level and for developing novel potential drugs using TCMs as lead compounds. Finally, we showed that SM-MBC was an efficient protocol for the rapid screening of mitochondria-targeting constituents from complex samples such as PR and CR extracts.

TWO new rotenoids from the root of Derris elliptica

二新 rotenoids 4 鈥 ? 5 鈥 ? dihydroxy-6a， 12a-dehydrodeguelin (1 ) ， 11,4 鈥 ? 5 鈥 ? trihydroxy-6a， 12a-dehydrodeguelin (2 ) ，与二已知的 rotenoids 一起，毒鱼藤素和 deguelin 从在广东省收集的鱼藤 elliptica 的根被孤立，中国。他们的结构被广泛的分光镜的分析建立。

Improved anti-tumor efficacy and pharmacokinetics of bufalin via PEGylated liposomes

OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.

A new sesquiterpene trilactone from the roots of Ginkgo biloba

新 sesquiterpene trilactone，命名 bilobanol (1 ) ，与四已知的萜烯一起， trilactones (ginkgolide A， B， C 和 bilobalide ) 从在江苏省收集的白果树 biloba 的根被孤立，中国。结构说明被 1D 和 2D NMR 完成方法， HR-ESI-MS，和 CD 光谱。

Two isomeric compounds of C_(13)-norisoprenoids from Saururus chinensis(Lour.) Baill

Two new isomeric compounds of rare acyclic C_(13)-norisoprenoids,along with two known lignans sauchinone and licarin A,were isolated from the herb of Saururus chinensis(Lour.) Baill.Their structures were elucidated on the basis of spectral analysis.

New limonoids from the fruits of Melia toosendan

二新 limonoids， 1 伪 - tigloyloxy-3 伪 - acetoxyl-7 伪 - hydroxyl-12 伪 - ethoxyl nimbolinin (1 ) 和 1 伪 - benzoyloxy-3 伪 - acetoxyl-7 伪 - hydroxyl-12 伪 - ethoxyl nimbolinin (2 ) ，从 Melia toosendan 的水果被孤立。他们的结构根据各种各样的 NMR 分光镜的分析被建立，包括 2D-NMR 技术(HSQC， HMBC， NOESY ) 并且 HR-ESI-MS。

Studies on the Structure of Kansuinine A from Euphorbia kansui

Kansuinine A is a macrocyclic jatrophane diterpene that was isolated from Euphorbia kansui. Further investigation of the structure was revealed that the benzoyl group located at C-8 and the position of C-3 was the present of an acetyl group by means of HMQC, HMBC spectra.

Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.

Study of electrospray ionization tandem mass spectrometry of the benzofuranone compounds

在多重双人脚踏车质谱学(ESI-MSn ) 下面的 benzofuranone 混合物的详细分析调节的 A 被报导。碎片离子的元素作文数据在哪个除了一些代替的组或 epimers 或 cis trans 异构体是相同的四混合物，和结构的多重双人脚踏车团系列的比较的帮助下被获得。被尝试了从这些质子 ated 混合物为碎片离子的形成提供合理小径。并且结构破碎关系将便于另外的类似物的结构的描述。

Compound Kushen injection induces immediate hypersensitivity reaction through promoting the production of platelet-activating factor via de novo pathway

OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.

Determination of the Absolute Configuration of Rohitukine

The absolute configuration of rohitukine, isolated from the stem-bark of Dysoxylum binectariferum, was determined to be 5,7-dihydroxy-2-methyl-8-[4-(3S, 4R-3-hydroxy-1-methyl) -piperidinyl]-4H-1-benzopyran-4-one by X-ray crystallographic analysis on the crystal of 4-bromobenzoyl derivatives of rohitukine. At the same time, the modified Mosher method was proved to be unsuitable for determining the absolute configuration of C-3 position in rohitukine.

Sebiferone,a New Triterpenoid from Stem Bark of Sapium sebiferum (L.)Roxb.

From the stem bark of Sapium sebiferum a new triterpenoid, named sebiferone (1), was isolated. The structure of the new compound was elucidated as 3β-acetoxy-D-friedoolen-14-en -1-one-28-oic acid on the basis of spectral and chemical methods.

Determination and stress studies on YK-1101,a potential histone deacetylase,by HPLC-UV and HPLC-TOF/MS methods

YK-1101,with its structure as S-((E)-4-((7S,10S,Z)-4-ethylidene-7-isopropyl-2,5,8,12tetraoxo-9-oxa-16-thia-3,6,13,18-tetraazabicyclo[13.2.1]octadeca-1(17),15(18)-dien-10-yl)but-3-en-1-yl) ethanethioate,is synthesized as a potential histone deacetylase inhibitor.Its quality and stability under various stress conditions are not fully understood.In this study,a high performance liquid chromatographic(HPLC) method was established and validated for the analysis of YK-1101 bulk drug samples.The chromatographic separation was performed on a C18 column with acetonitrile and water as mobile phase in a gradient elution.Based on the established method,the stability studies of YK-1101 under various stress conditions were carried out.YK-1101 was shown to undergo degradation under basic and acidic stress conditions,while it was stable under oxidative,photolytic and thermal conditions.In addition,a time of flight mass spectrometer(TOF/MS) was coupled to HPLC for the characterization of major degradation products produced under basic and acidic stress conditions.Their degradation pathways were also discussed.

Synthesis of 2-aryl-5-alkyl-7-methoxylbenzo[b]furan derivatives

A series of 2-aryl-5-alkyl-7-methoxylbenzo[b]furan derivatives have been synthesized by utilizing the coupling of methyl 3-methoxy-4-hydroxy-5-bromocinnamate with cuprous phenylacetylide as the key step.The structures of the new compounds were confirmed by1H NMR,IR and MS.The structure of compound 14 was further confirmed by single crystal X-ray.Compound 17 showed cytotoxic activity against human lung carcinoma A549.

~1H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic changes of gastrodin intervention in rats

Objective:To explore^1H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats.Methods:In this research,~1H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats.Results:24 endogenous metabolites were identified.Body weight.daily diet and the total volume of urine in in each day of each rat were measured synchronously.Modifications in 12 metabolites were observsd following gastrodin intervention,indicating gastrodin-induced alterations in carbohydrate and energy metabolism.Interestingly,these metabolic changes were not totally identical in female and male rats.Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male,together with arginine/ornithine,creatine,and glycerol which were on the increase in the female but on the decrease in the male.While the decrease in pyruvate,succinate and glutamate was only shown in the male and the increase in valine,α-ketoglutarate and glucose was only in the female.Conclusions:This resesrch shows the sex-specific metabolic response to GAS intervention,weather GAS is a healthy dietary supplement for the male merits further

Isolation, Crystal Structure and Na^＋/K^＋-ATPase Inhibitory Activity of 1β-Hydroxydigitoxigenin

The title compound 1β-hydroxydigitoxigenin(1) was isolated from the ethanol extract of the roots of Streptocaulon juventas. The crystal structure of 1, C_(23)H_(34)O_5·H_2O, was determined by Synchrotron X-ray diffraction analysis due to small crystal size(0.14 mm × 0.04 mm × 0.01 mm). The crystal belongs to monoclinic, space group P21, with a = 7.6624(15), b= 13.460(3), c = 10.370(2) ?, b = 92.40(3)°, V = 1068.6(4) ?3, Z = 2, Mr = 406.50, Dx = 1.263 g/cm3, λ(synchrotron) = 1.2399 ?, μ(synchrotron 1.23990) = 0.333 cm^(-1), F(000) = 550, S = 1.059, R = 0.0625 and w R = 0.1687 for 4247 unique reflections, of which 3687 were observed(I > 2σ(I)). The asymmetric unit contains one independent molecule of 1 and one water molecule which are connected through hydrogen bonds. The conformation of 1 in crystalline state is in good agreement with the solution structure in methanol as indicated by ~1H-NMR analysis. The absolute configuration of 1 could be assigned by referring to the known configuration of the lactone ring at C(17b). In the solid state, intermolecular hydrogen bonds involving carbonyl group in the lactone moiety and the hydroxyl groups in the steroid moiety ester linked adjacent molecules into a three-dimensional network. Compound 1 showed significant inhibition on Na+/K+-ATPase with an IC50 of 2.46 mM, which is stronger thiocarbonylbufalin but weaker than a close analog digitoxigenin, suggesting that a lactone ring is important and the substitution of a hydroxyl group at C(1) is not favored for the inhibition of Na^+/K^+-ATPase.