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Ethnopharmacological relevance The plants in the genus Gleditsia, mainly distributed in central and Southeast Asia and North and South America, have been used as local and traditional medicines in many regions, especially in China, for the treatment of measles, indigestion, whooping, smallpox, arthrolithiasis, constipation, diarrhea, hematochezia, dysentery, carbuncle, etc. This present paper systemically reviews the miscellaneous information surrounding its traditional use, phytochemistry and pharmacology to provide opportunities and recommendations for the future research. Materials and methods The scientific literatures were systematically searched from scientific databases (PubMed, Scopus, Elsevier, SpringerLink, SciFinder, Google Scholar and others). In addition, the ethnopharmacological information on this genus was mainly acquired from Chinese and Korean herbal classics, and library catalogs. Results More than 60 compounds including triterpenes, sterols, flavonoids, alkaloids, phenolics and their derivatives were isolated from Gleditsia japonica Miq., Gleditsia sinensis Lam., Gleditsia caspica Desf. and Gleditsia triacanthos L. Among these compounds, triterpenoid saponins were the main constituents of Gleditsia species. Moreover, the crude extracts and purified molecules were tested, revealing diverse biological activities such as anti-tumor, anti-inflammatory, anti-allergic, anti-hyperlipidemic, analgesic, antimutagenic, antioxidant, anti-HIV, antibacterial, antifungal activities, etc. Among these biological studies, the possible mechanisms of antitumor action are stressed in this review, and these include causing cytotoxicity to cancer cells, inhibition of proliferation of cancer cells by affecting their growth, regeneration and apoptosis, inhibition of basic fibroblast growth factor (bFGF) and nitric oxide (NO), modulation of the oncogenic expression and telomerase activity results, inhibition of the expression of pro-angiogenic proteins, as well as down-regulation of intra/extracellular proangiogenic modulators, etc. Conclusions On the basis of preliminary research on Gleditsia genus it could be stated that saponins investigations may be more promising in future. Although 32 compounds of 67 identified compounds were saponins, modern pharmacological research on saponins were not a priority in Gleditsia species. Therefore, more bioactive experiments and in-depth mechanisms of action are required for elucidating their roles in physiological systems. Moreover, the present review also highlights that analgesic, anti-tumor and anti-HIV activities should have priority in saponins research. Additionally, it is imperative to explore more structure–activity relationships and possible synergistic actions of triterpenoid saponins for revaluating their pharmacological activities.

isolation, structure determination, antiinflammatory and antitumor activity of seven new diterpenoids, lanceolatins A—G (I)—(VI), along with five known diterpenoids

Ethylene-insensitive3/ethylene-insensitive3-like (EIN3/EIL) transcription factor is a key transcription factor involved in the ethylene signal transduction pathway in plants. Although the genome-wide analysis of this family has been carried out in certain plant species, little is known about EIN3/EIL genes in rubber tree (Hevea brasiliensis). In this study, we identified four EIN3/EIL genes (designated as HbEIN3-1 to HbEIN3-4) in the rubber tree genome annotation. Tissue-specific expression profiles showed that four HbEIN3s were expressed in at least one of the tested tissues. The four HbEIN3s responded to ethylene (ET) and jasmonic acid (JA) treatment, which suggested that HbEIN3s were involved in response to JA and ET signaling. HbEIN3s showed transactivation activity in yeast. HbEIN3-1 bound to the promoter of the rubber transferase gene, suggesting that HbEIN3-1 may be involved in the regulation of natural rubber biosynthesis. The N-terminal basic domain II was required for the HbEIN3-1 binding with the promoter of the rubber transferase gene.

Valepotriates, plant secondary metabolites of the family Valerianaceae, contain various acyloxy group linkages to the valepotriate nucleus and exhibit significant biological activities. Identification of valepotriates is important to uncover potential lead compounds for the development of new sedative and antitumor drugs. However, making their structure elucidation by nuclear magnetic resonance (NMR) experiments is too difficult to be realized because of the overlapped carbonyl carbon signals of acyloxy groups substituted at different positions. Thus, the mass spectrometric profiling of these compounds in positive ion mode was developed to unveil the exact linkage of acyloxy group and the core of valepotriate. In this study, electrospray ionization tandem multistage mass spectrometry (ESI-MS/MS(n)) in ion trap and collision-induced dissociation tandem MS were used to investigate the fragmentation pathways of four types of valepotriates in Valeriana jatamansi, including 5-hydroxy-5,6-dihydrovaltrate hydrin (5-hydroxy-5,6-dihydrovaltrate chlorohydrin), 5,6-dihydrovaltrate hydrin (5,6-dihydrovaltrate chlorohydrin), 5-hydroxy-5,6-dihydrovaltrate and valtrate hydrin (valtrate chlorohydrin). The high-resolution mass spectrum (HRMS) data of all the investigated valepotriates from quadrupole time-of-flight MS/MS were used as a supportive of the fragmentation rules we hypothesized from ion-trap stepwise MS(n). As a result, the loss sequence of acyloxy groups and the abundance of key product ions, in combination with the characteristic product ions corresponding to the valepotriate nucleus, could readily differentiate the four different types of valepotriates. The summarized fragmentation rules were also successfully exploited for the structural characterization of three new trace valepotriates from V. jatamansi. The results indicated that the developed analytical method could be employed as a rapid, effective technique for structural characterization of valepotriates, especially for the trace compounds that could not be identified by NMR techniques. This study may also arouse interest for further structural analysis of other valepotriate-containing type herbal medicines.

The cytotoxic activity of merrilliadione (I) is moderate against several human cancer cell lines.

Four new isomeric sesquiterpene lactone dimers, carpedilactones A (I), B (II), C (III), and D (IV) are isolated.

Two new xanthones, 1,6-dihydroxyisojacereubin-5-O-beta-D-glucoside (1) and 3,6,7-tri-hydroxy-1-methoxy-xanthone (2), were isolated from Hypericum japonicum. The structural elucidation of the isolated compounds were primarily based on HREIMS, EIMS, UV, IR, 1D-, and 2D-NMR analyses, including COSY, HMQC, HMBC, and NOESY correlations.

Astragaloside IV is the major active constituent of Astragalus membranaceus, which has been widely used for the treatment of cardiovascular diseases in China. However, the effects of astragaloside IV on myocardial ischemia and its mechanisms of action remain largely unknown. In this study, we have examined the effects of astragaloside IV on myocardial infarction and coronary flow in vivo and in vitro. The possible roles of its antioxidative and nitric oxide-inducing properties were also explored. Astragaloside IV significantly reduced infarct size in dogs subjected to coronary ligation in vivo. Astragaloside IV also improved post-ischemic heart function and ameliorated reperfusion arrhythmias in rat hearts in vitro. The cardioprotection of astragaloside IV was accompanied by a significant increase in coronary flow both in vivo and in vitro. The nitric oxide synthase inhibitor, Nomega-nitro- L-arginine methyl ester partially abrogated astragaloside IV's protective effect on heart function. Myocardial antioxidative enzyme superoxide dismutase activity increased with astragaloside IV administration. These data suggest the potential roles of antioxidative and nitric oxide-inducing properties of astragaloside IV in its protection from myocardial ischemia.

Two new thiazinediones along with five known compounds were isolated from the fruits of Xanthium strumarium L. The structures of the two new compounds were determined to be 7-hydroxymethyl-8,8-dimethyl-4,8-dihydrobenzol[1,4]thiazine-3,5-dione-11-O-β-D-glucopyranoside (1) and 2-hydroxy-7-hydroxymethyl-8,8-dimethyl-4,8-dihydrobenzol[1,4]thiazine-3,5-dione-11-O-β-D-glucopyranoside (2). The five known compounds were identified as xanthiazone (3), chlorogenic acid (4), ferulic acid (5), formononetin (6), and ononin (7), respectively.

Summary Background Mesenchymal stem cells (MSC) have the capacity to differentiate into cells of connective tissue lineages, including bone, fat, cartilage and muscle, but the differentiation of embryonic MSC into epidermal cells by mesenchymal-epithelial transition has not been confirmed. Objectives To determine the biological characteristics of human embryonic MSC (hMSC) and their potential for differentiation into epithelial cells. Methods hMSC were derived from 4–7-week-old embryos; they were localized and isolated, then primary culture was done. The biological characteristics of hMSC were detected by immunohistochemical methods and flow cytometry. Their differentiation potential was determined by coculture with conditioning medium and in vivo injection. Results hMSC express the relative specific antigens of MSC, such as SH2, α-smooth actin, CD29, CD44, CD90 and S100. After stimulation and in vivo transplantation, hMSC possess the potential to differentiate into epidermal cells with the production of keratin 19 and E-cadherin. Conclusions hMSC derived from the early human embryo have the ability to transform into epidermal cells in vivo and in vitro.

Corydalis saxicola Bunting (Yanhuanglian) is an important component in various prescriptions in traditional Chinese medicine. Yanhuanglian has been demonstrated to possess many pharmacological activities, including antibacterial, antiviral and anticancer activities. The active fractions are dehydrocavidine, coptisine, dehydroapocavidine and tetradehydroscoulerine. The purpose of the present study was to examine in vivo pharmacokinetics and tissue distribution in rats by using high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry. Systemic clearance of the four active alkaloids in plasma was over 93% of hepatic blood flow, indicating they may be quickly eliminated via hepatic clearance. Less than 10% drugs was excreted via urine following intravenous and oral administration, suggesting that these four alkaloids may undergo significant metabolism in the body or the drug may be excreted via other routes other than urine. There was significantly lower excretion of these four alkaloids following oral than intravenous administration, suggesting a significant first pass effect after oral administration. There appeared to be wide distribution of those four alkaloids in rats as demonstrated by the higher apparent volume of distribution. Our results have also demonstrated that the four alkaloids can be absorbed following oral administration although there were less than 15% of drugs absorbed into systemic circulation. In summary, the favorable oral bioavailability properties of those four active alkaloids in rats make Yanhuanglian extract worth further investigation for improving oral bioavailability.

A sensitive rapid method for the simultaneous determination of four major active alkaloids (dehydrocavidine, coptisine, dehydroapocavidine, and tetradehydroscoulerine, in abbreviation thereafter called YHL-I, YHL-II, YHL-III, and YHL-IV, respectively) from a Chinese traditional medicine Corydalis saxicola Bunting. (Yanhuanglian) in rat plasma and urine was established and validated. The assay for these substances in plasma and urine was based on HPLC coupled with tandem mass spectrometry (MS/MS) detection using multiple reaction monitoring mode (MRM) with berberine and clenbuterol as internal standards. The plasma and urine sample were deproteinated by adding methanol prior to liquid chromatography where separation was performed on a Luna column (5 microm, 100 x 2.00 mm) and an Agilent Zorbax SB-C18 guard column (5 microm, 20 x 4 mm). The method was validated with the concentration range 1-1000 ng/mL in plasma and 10-1000 ng/mL in urine for the four test compounds, and the calibration curves were linear with correlation coefficients >0.999. The lowest limits of quantitation for all four substances were 1 ng/mL in 0.1 mL rat plasma and 10 ng/mL in 0.1 mL urine. The intra-assay accuracy and precision in plasma ranged from 88.1 to 115.7% and 1.4 to 10.8%, respectively, while inter-assay accuracy and precision for YHL-I, YHL-II, YHL-III, and YHL-IV ranged from 96.2 to 113.2% and 0.4 to 16.9%, respectively. The intra-assay accuracy and precision for YHL-I, YHL-II, YHL-III, and YHL-IV in rat urine ranged from 96.1 to 112.9% and 1.2 to 8.3%, respectively, while inter-assay accuracy and precision ranged from 95.0 to 106.8% and 2.2 to 10.3%, respectively. The method was further applied to assess pharmacokinetics and urine excretion of the four alkaloids after oral and intravenous administration to rats. Practical utility of this new LC-MS-MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration.

Despite great advancements in the treatment of non-Hodgkin lymphoma (NHL), sensitivity of different subtypes to therapy varies. Targeting the aberrant activation NF-κB signaling pathways in lymphoid malignancies is a promising strategy. Here, we report that 11(13)-dehydroivaxillin (DHI), a natural compound isolated from the Carpesium genus, induces growth inhibition and apoptosis of NHL cells. Multiple signaling cascades are influenced by DHI in NHL cells. PI3K/AKT and ERK are activated or inhibited in a cell type dependent manner, whereas NF-κB signaling pathway was inhibited in all the NHL cells tested. Applying the cellular thermal shift assay, we further demonstrated that DHI directly interacts with IKKα/IKKβ in NHL cells. Interestingly, DHI treatment also reduced the IKKα/IKKβ protein level in NHL cells. Consistent with this finding, knockdown of IKKα/IKKβ inhibits cell proliferation and enhances DHI-induced proliferation inhibition. Overexpression of p65, p52 or RelB partially reverses DHI-induced cell growth inhibition. Furthermore, DHI treatment significantly inhibits the growth of NHL cell xenografts. In conclusion, we demonstrate that DHI exerts anti-NHL effect in vitro and in vivo, through a cumulative effect on NF-κB and other pathways. DHI may serve as a promising lead compound for the therapy of NHL.

Four new isomeric sesquiterpene lactone dimers, carpedilactones A-D (1-4), were isolated from the acetonic extract of Carpesium faberi. Among them, 1-3 are the first three 2,4-linked exo-Diels-Alder adducts between a eudesmanolide dienophile and a guaianolide diene. The absolute configurations of 1-4 were unambiguously established by Cu Kα X-ray crystallographic analyses. Compounds 1-4 exhibited potent cytotoxicities against human leukemia (CCRF-CEM) cells with IC50 value of 0.14, 0.32, 0.35, and 0.16 μM, respectively.

Valeneomerins A-D [(I)-(III)] are isolated and screened for their neuroprotective activities on hydrogen peroxide-induced apoptosis in human neuroblastoma SH-SY5Y cell lines.

The 14-3-3 proteins are a family of conserved phospho-specific binding proteins involved in diverse physiological processes. Although the genome-wide analysis of this family has been carried out in certain plant species, little is known about 14-3-3 protein genes in rubber tree (Hevea brasiliensis). In this study, we identified 10 14-3-3 protein genes (designated as HbGF14a to HbGF14j) in the latest rubber tree genome. A phylogenetic tree was constructed and found to demonstrate that HbGF14s can be divided into two major groups. Tissue-specific expression profiles showed that 10 HbGF14 were expressed in at least one of the tissues, which suggested that HbGF14s participated in numerous cellular processes. The 10 HbGF14s responded to jasmonic acid (JA) and ethylene (ET) treatment, which suggested that these HbGF14s were involved in response to JA and ET signaling. The target of HbGF14c protein was related to small rubber particle protein, a major rubber particle protein that is involved in rubber biosynthesis. These findings suggested that 14-3-3 proteins may be involved in the regulation of natural rubber biosynthesis.

The genus Xanthium (Compositae) is represented by 25 species in the world and 3 species and 1 variety in China [1]. These are X. sibiricum Patr. (X. strumarium L.), X. mongolicum Kitag., X. inaequilaterum DC., and X. sibiricum var. subinerme (Winkl.) Widder. Xanthium species have been used as traditional herbal medicines for the treatment of nasal sinusitis, headache caused by wind-cold, urticaria, and arthritis for a long time in oriental countries [2]. The chemical composition of ent-kaurane diterpenoids, sesquiterpene lactones, caffeoylquinic acids, and thiazinediones from this genus (leaves or fruits) has been reported [3–8]. Chemical examination of the essential oil from the leaves of Xanthium strumarium showed that the main components of the essential oil were d-limonene and d-carveol, with a relative content of 35% and 25% (w/w), respectively [9]. The composition of the fruit essential oil of Xanthium sibiricum Patr. was reported in 1994 [10], and showed that saturated paraffin hydrocarbons such as eicosane and nonadecane were the major components. The fruit oil of Xanthium obtained by crushing were reported to have anti-thrombus effects and to decrease blood-fat in civil use [11], which were referred to the lipophylic extracts of Xanthium fruits. The purpose of this research was to conduct a comparative analysis on the fatty oil composition from samples belonging to three Xanthium species growing in China: X. sibiricum, X. sibiricum var. subinerme, and X. mongolicum. The collected location and date of the three Xanthium species used for supercritical fluid extraction (SFE) and GC-MS analysis are listed in Table 1. This is the first report on the lipophylic extracts prepared by SFE of the three Xanthium species. The results of the fatty acid analysis by GC-MS and the oil yield of the taxa are presented in Table 1. The extraction of essential oil components using solvents at high pressure, or supercritical fluids, has received much attention in the past several years, especially in the food, pharmaceutical, and cosmetic industries, because it presents an alternative to conventional processes such as organic solvent extraction and steam distillation [12, 13]. By comparing the composition of the product with hydrodistilled oil [14], higher levels of the volatile components such as d-limonene and d-carveol were found by using the hydrodistillation method [9]. However, these compounds were not found in the SFE products. In contrast, the fatty acids linoleic acid, palmitic acid, stearic acid, and some sterols were found in the SFE products, whereas negligible amounts were present in the distilled oils. In this study, a total of 37 compounds of three Xanthium species in China was determined, of which aromadendrene, α-phellandrene, globulol, norphytane, tomentosin, etc. were identified from Xanthium genus for the first time. The fatty oil composition of the studied Xanthium genus was not uniform but overlap. A considerable content of linoleic acid and palmitic acid was noted in all samples, but small quantitative differences were also found. Linoleic acid was the predominant constituent of the studied fruit oil and had the relative content of 80.24% (X. sibiricum), 70.75% (X. sibiricum var. subinerme) and 77.71% (X. mongolicum), respectively. The amount of linoleic acid is important with respect to the quality of the oils consumed as a food resource [15]. Therefore, the fruits of the three studied Xanthium species can all be regarded as a new resource for linoleic acid production. Stearic acid, linolenyl alcohol, n-tetracosane, n-pentacosane, and n-nonacosane, were present in both X. sibiricum var. subinerme and X. mongolicum fruit oil. The X. sibiricum var. subinerme oil composition was characterized by a large variation of the long-chain diolefins, including n-heptadecane, n-docosane, and all the linear-chain diolefin froms n-tetracosane to n-nonacosane. Only nine compounds of X. mongolicum fruit oil were determined, of which diisooctyl phthalate was the special component.

A new phenolic compound was isolated from the ethanol extract of the bulbs of Crinum asiaticum L. var. sinicum Baker. Its structure was defined as 1-(2-hydroxy-4-hydroxymethyl)phenyl-6- O -caffeoyl-β- d -gluco-pyranoside on the basis of spectroscopic evidences.

Two new bis-coumarin glycosides were isolated from the stem barks of Daphne giraldii NITSCHE. Their structures were elucidated as 6-O-alpha-L-rhamnnopyranosyl daphnogirin (1), and 6-O-beta-D-apiofuranosyl daphnogirin (2), on the basis of detailed spectroscopic analysis. Compounds 1 and 2 were tested inhibitory effects against production of nitric oxide (NO) in RAW264.7 cells, and cytotoxicity of human tumor cell lines A549, LOVO, QGY-7703, 6T-CEM. The results showed that compounds 1 and 2 neither reduced production of NO, nor inhibited human tumor cell lines.

Thirteen tetrahydroprotoberberines, 2,9,10-thrihydroxy-3-methoxytetrahydroprotoberberine (1), cavidine (2), thalictrifoline (3), mesotetrahydrocorysamine (4), stylopine (5), sinactine (6), apocavidine (7), cheilanthifoline (8), 13-β-hydroxystylopine (9), tetrahydropalmatine (10), tetrahydropalmatrubine (11), isocorypalmine (12), and scoulerine (13) have been isolated from the herb of Corydalis. Saxicola Bunting. Of these alkaloids, 2,9,10-thrihydroxy-3-methoxytetrahydroprotoberberine (1) was a new base. The alkaloids mesotetrahydrocorysamine (4), stylopine (5), sinactine (6), apocavidine (7), cheilanthifoline (8), 13-β-hydroxystylopine (9), tetrahydropalmatine (10), tetrahydropalmatrubine (11), isocorypalmine (12), and scoulerine (13), although previously known, were isolated for the first time from Corydalis saxicola Bunting.

Small GTPases play a critical role in the regulation of a range of cellular processes including growth, differentiation, and intracellular transportation. The cDNA encoding a small GTPase, designated as HbGTPase1, was isolated from Hevea brasiliensis. HbGTPase1 was 882 bp long containing a 612-bp open reading frame encoding a putative protein of 203 amino acids, flanked by an 83-bp 5'-untranslated region (UTR) and a 187-bp 3'-UTR. The predicted molecular mass of HbGTPase1 is 22.62 kDa, with an isoelectric point of 5.06. The HbGTPase1 protein was predicted to possess the conserved functional regions of the small GTPase superfamily of proteins. Quantitative polymerase chain reaction analysis revealed that HbGTPase1 was constitutively expressed in all tissues tested. HbGTPase1 transcripts accumulated at relatively low levels in the flower, latex, and leaves, while HbGTPase1 transcripts accumulated at relatively high levels in bark. Transcription of HbGTPase1 in the latex was induced by jasmonate.

Small rubber particle protein (SRPP) is a major component of Hevea brasiliensis (H. brasiliensis) latex, which is involved in natural rubber (NR) biosynthesis. However, little information is available on the regulation of SRPP gene (HbSRPP) expression. To study the transcriptional regulation of HbSRPP, the yeast one-hybrid experiment was performed to screen the latex cDNA library using the HbSRPP promoter as bait. One cDNA that encodes the WRKY transcription factor, designated as HbWRKY1, was isolated from H. brasiliensis. HbWRKY1 contains a 1437 bp open reading frame that encodes 478 amino acids. The deduced HbWRKY1 protein was predicted to possess two conserved WRKY domains and a C2H2 zinc-finger motif. HbWRKY1 was expressed at different levels, with the highest transcription in the flower, followed by the bark, latex, and leaf. Furthermore, the co-expression of pHbSRP::GUS with CaMV35S::HbWRKY1 significantly decreased the GUS activity in transgenic tobacco, indicating that HbWRKY1 significantly suppressed the HbSRPP promoter. These results suggested that HbWRKY1 maybe a negative transcription regulator of HbSRPP involved in NR biosynthesis in H. brasiliensis.

Incarvilleatone (1), an unprecedented dimeric cyclohexylethanoid analog with a racemic nature, was isolated from the whole plant of Incarvillea younghusbandii. HPLC chiral separation of 1 gave two enantiomers (−)-incarvilleatone and (+)-incarvilleatone. The structure of 1 was established by spectroscopic methods and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. (−)-Incarvilleatone exhibited a potent inhibitory effect against NO production in LPS-induced RAW264.7 macrophages.

HPLC-PDA-MS and TLC analysis were used to look for minor cytotoxic chlorinated valepotriates from whole plants of Valeriana jatamansi (syn. Valeriana wallichii DC.). This resulted in isolation of 15 chlorinated valepotriates, designated as chlorovaltrates A-O, together with six known analogues, (1S,3R,5R,7S,8S,9S)-3,8-epoxy-1,5-dihydroxyvalechlorine, volvaltrate B, chlorovaltrate, rupesin B, (1S,3R,5R,7S,8S,9S)-3,8-epoxy-1-O-ethyl-5-hydroxyvalechlorine, and (1R,3R,5R,7S,8S,9S)-3,8-epoxy-1-O-ethyl-5-hydroxyvalechlorine. Their structures were elucidated by spectroscopic methods including homo- and heteronuclear two-dimensional NMR experiments. Chlorovaltrates K-N, chlorovaltrate and rupesin B showed moderate cytotoxicity against lung adenocarcinoma (A 549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8) and hepatoma (Bel 7402) cell lines with IC₅₀ values of 0.89-9.76 μM.

Objective To investigate the chemical constituents from the whole plants of Senecio chrysanthemoides. Method Constituents were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and ODS C18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic and chemical methods. Result Eighteen glycosides were obtained from a H2O-soluble portion of an ethanolic extract of the whole plants of Senecio chrysanthemoides and their structures were elucidated as 5'-methoxyligusinenoside B (1), hyuganoside III b (2), citrusin A (3), alaschanioside A (4), citrusin B (5), dehydrodieoniferyl alcohol 4, gamma'-di-O-beta-D-glucopyranoside (6), osmanthuside G (7), syringin (8), dehydrosyringin (9), 2-(4-hydroxy-3,5-dimethoxyphenyl) ethanol 4-O-beta-D-glucopyranoside (10), 2-phenylethyl beta-gentiobioside (11), phenethyl beta-D-glucopyranoside (12), nikoenoside (13), benzyl beta-D-glucopyranoyl (1 --> 6 ) -beta-D-glucopyranoside (14), 3,5-dimethoxy-4-hydroxybenzyl alcohol 4-O-beta-D-glucopyranoside (15), icariside B2 (16), sonchuionoside C (17), and 1-[(beta-D-glucopyranosyloxy) methyl] -5,6-dihydropyrrolizin-7-one (18). Conclusion Compound 1 was a new lignan glycoside, and the remaining compounds were obtained from this plant for the first time.

The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR) study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157). Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others.

Three new cyclic peptides, tunicyclins B-D, and a known cyclic peptide, psammosilenin B, were isolated from the root of Psammosilene tunicoides. The structures of new cyclic peptides were elucidated by extensive NMR and MS analysis. Tunicyclin B contains an unusual alpha,beta-dehydrotryptophan (Delta(Z)-Trp) residue, previously reported from marine sponges and bacteria. Tunicyclin D showed a broad spectrum of antifungal activity against Candida albicans (SC5314), Candida albicans (Y0109), Candida tropicalis, Candida parapsilosis, and Cryptococcus neoformans (BLS 108) with MIC80 values of 4.0, 16.0, 0.25, 1.0, and 1.0 mu g mL(-1), respectively.

The structures of 1,5-dihydroxy-3,8-epoxyvalechlorine (1a) and volvaltrate B (6a), two new chlorinated iridoids isolated from Valeriana jatamansi and V. officinalis, respectively, were originally assigned on the basis of spectroscopic methods. Reinvestigation using X-ray analysis and chemical transformation revealed that the original assignment of H-7 in 1a and OH-8 in 6a should be inverted and that the structures should be revised to 1 and 6, respectively. Correspondingly, the structure of valeriotetrate C (7a) should be revised to 7. Volvaltrate B (6) showed cytotoxic activity against the lung adenocarcinoma (A549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8), and hepatoma (Bel7402) cell lines, with IC50 values of 8.5, 2.0, 3.2, and 6.1 μM, respectively.

Three new monoterpene alkaloids, mairine A (1), mairine B (2), and mairine C (3), and a new caffeic acid ester, 2-(1-hydroxy-4,4-dimethoxycyclohexyl)ethyl caffeate (4), were isolated from the EtOH extract of the whole plants of Incarvillea mairei var. multifoliolata. The structures of these compounds were established on the basis of 1D- and 2D-NMR and HR-ESI-MS analysis.

OBJECTIVE To investigate the chemical constituents from the whole plants of Senecio chrysanthemoides. METHOD The chemical constituents were isolated and purified by chromatographic techniques over silica gel, Sephadex LH-20, preparative TLC and preparative HPLC. Structures of the compounds were identified by NMR and MS spectroscopic methods. RESULT Twenty five compounds were obtained and their structures were elucidated as seneciphyline (1), senecionine (2) , 1,2-dihydrocacalohastine (3) , eu-desm-4( 15)-ene-1beta,6alpha-diol (4), 7,11,15-trimethyl- 3methylidenehexadecane-1,2-diol (5), faradiol 3-O-palmitate (6),maniladiol 3-O-palmitate (7), faradiol (8), maniladiol (9), beta-amyrin (10), alpha-amyrin (11), betulin (12), loranthol (13), (+)-syringaresinol (14) , 1-hydroxy-4-oxo-cyclohexane-1-acetate (15), 2, 6-dimethoxy-p-benzoquinone (16), stigmasta-5, 22-dien-3beta-hydroxy-7-one (17) , stigmasta-5, 22-dien-7-one (18) , stigmasta-4-en-3-one (19), stigmasta-4,22-dien-3-one (20), beta-sitosterol (21), stigmasterol (22), daucosterol (23), glycerol 1-hendecanoate (24), and methyl hendecanoate (25). CONCLUSION Compounds 5-9,13, 17-20 and 24 were obtained from the genus Senecio for the first time.

A new furostanol saponin, (25S)-26-O-β-D-glucopyranosyl-5β-furost-20(22)-en-3β, 15β,26-triol-3-O-[α-L-rhamnopyranosyl-(1-4)]-β-D: -glucopyranoside, namely, aspacochioside D (1) were isolated from Asparagus cochinchinensis (Lour.) Merr, along with three known saponins, aspacochioside C (2), (25S)-5β-spirostan-3β-yl-O-[O-α-L-rhamnopyranosyl-(1-4)]-β-D-glucopyranoside (3), and pseudoprotoneodioscin (4). The structure of 1 was elucidated on the basis of chemical reactions and spectral analysis (IR, GC, ESI-MS, (1)H-NMR, (13)C-NMR, DEPT, HMBC, HMQC and NOESY). The antiproliferative effects of 1-4 were evaluated in a cytotoxicity assay against the human tumor cell line, A549. Compound 2 (Aspacochioside C) exhibited moderate cytotoxicity against A-549, with an IC(50) value of 3.87 μg/mL.

Three MADS-box genes, designated HbMADS1, HbMADS2 and HbMADS3, were isolated from Hevea brasiliensis. HbMADS1, HbMADS2 and HbMADS3 encode polypetides consisting of 245, 217 and 239 amino acids, respectively, containing conserved MADS-box motifs at N-terminus. Transcription pattern analysis revealed that three MADS-box genes had highly transcription in the laticifer cells. The transcriptions of HbMADS1and HbMADS3 were induced in the laticifer cells by jamonic acid, while HbMADS2 was not induction by jamonic acid. Ethephone is not effective in inducing their expression. The three genes were differentially expressed during somatic embryogenesis of rubber tree. Characterization of HbMADSs will attribute to understand their possible function in rubber tree.

Two new alkaloids, incarvines E (1) and F (2), were isolated from the EtOH extract of the whole plant of Incarvillea sinensis. Their structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR.

Ten steroidal alkaloids - cyclopamine, veratramine, jervine, 3, 15-diangyloylgermine, 3-angyloylzygadenine, 3-veratroyl zygadenine, 15-veratroylgermine, germine, veratrosine and pseudojervine - from Veratrum dahuricum, together with the ethanol extract and total alkaloids, were evaluated for their antitumor and antiplatelet activities. Cyclopamine, veratramine and germine significantly inhibited the hedgehog pathway in NIH/3T3 cells. Cyclopamine exerted a potent inhibitory effect against the growth of PANC-1 tumors in mice, with inhibition rates of 40.64%, 44.37%, 46.77% at doses of 5.0, 15.0 and 50.0 mg kg-1, respectively. Veratroylgermine was found to produce the strongest inhibition against the platelet aggregation induced by arachidonic acid, with inhibition rate of 92.0% at 100 microM.

Monoclonal antibody M26-32 has been shown to strongly inhibit the growth of Plasmodium falciparum in vitro. To identify the target antigen of M26-32, a P. falciparum Dd2 asexual stage cDNA expression library was screened with this antibody, and a full open reading frame cDNA was obtained. This gene, named pfmag-1, encodes a polypeptide of 589 amino acids. The protein PfMAg-1 was characterized as a membrane-associated protein that expressed on the surface of merozoite during erythrocytic stage. Remarkably, at the C terminus of PfMAg-1, there are 14 copies of a deca-peptide sequence of QTDEIKND (H/N) I. This tandem repeat domain was identified to harbor the epitope of the protective M26-32 monoclonal antibody, and was also recognized by sera of patients infected with P. falciparum. Rabbit antibody elicited against this deca-peptide repeat domain effectively inhibited P. falciparum invasion in vitro. Our work suggests that PfMAg-1 is a promising malaria vaccine candidate.

Two new and three previously known CIS-clerodane diterpenoids were isolated from the wild liverwort Gottschelia schizopleura (Jungermanniales, Jungermanniaceae). Their structures were established on the basis of spectroscopic analysis, especially 1D and 2D NMR data. The cytotoxic activities of compounds 1- 5 were evaluated against liver hepatoblastoma (HEP-G2), lung carcinoma (A549), breast ductal carcinoma (MDA-MB-435), and colon adenocarcinoma (LOVO) cell lines. Compound 1 showed moderate inhibition against MDA-MB-435 and LOVO cells.

Thirteen new acylated iridoids, jatamanvaltrates A-M (1-13), together with nine known valepotriates (14-22), were isolated from the whole plants of Valeriana jatamansi (syn. Valeriana wallichii). The structures of these new compounds were assigned by detailed interpretation of spectroscopic data. Jatamanvaltrates D (4) and H (9) are the first examples of naturally occurring valepotriates containing an o-hydroxybenzoyloxy moiety at C-10. All isolated compounds were tested for their cytotoxicity against lung adenocarcinoma (A549), metastatic prostate cancer (PC-3M), colon cancer (HCT-8), and hepatoma (Bel7402) cell lines.

The full-length cDNA encoding a cysteine protease, designated HbCP1, was isolated for the first time from Hevea brasiliensis by the rapid amplification of cDNA ends (RACE) method. HbCP1 contained a 1371 bp open reading frame encoding 457 amino acids. The deduced HbCP1 protein, which showed high identity to cysteine proteases of other plant species, was predicted to possess a putative repeat in toxin (RTX) domain at the N-terminal and a granulin (GRAN) domain at the C-terminal. Southern blot analysis indicated that the HbCP1 gene is present as a single copy in the rubber tree. Transcription pattern analysis revealed that HbCP1 had high transcription in laticifer, and low transcription in bark and leaf. The transcription of HbCP1 in latex was induced by ethylene and tapping. Cloning of the HbCP1 gene will enable us to further understand the molecular characterization of cysteine protease and its possible function in the rubber tree.

A new flavonoid glycoside, 5-methoxy-7-beta-D-glucopyranosyl-(-)-afzelechin (1), together with seven known flavonoids, 7-O-beta-D-glucopyranosyl-(-)-epiafzelechin (2), sakuranin (3), genkwanin (4), 4',5-dihydroxy-3',7-dimethoxyflavone (5), luteolin-3',7-dimethyl ether-5-beta-D-glucoside (6), and luteolin-7-methyl ether-5-beta-D-glucoside (7), were isolated from the stem barks of Daphne giraldii. Their structures were identified on the basis of spectroscopic analysis. Compounds 2, 3, and 5-8 were first reported from the titled plant.

A phytochemical investigation of Ainsliaea macrocephala led to the isolation of a new dimeric sesquiterpene lactone, ainsliadimer A (1). The structure of 1 was elucidated by spectroscopic analysis, and confirmed by single crystal X-ray diffraction. Ainsliadimer A represents an unusual carbon skeleton with a cyclopentane system connecting the two monomeric sesquiterpene lactone units. This unique molecule exerted potent inhibitory activity against the production of nitric oxide in RAW264.7 stimulated by LPS.

A phytochemical investigation of Ainsliaea macrocephala led to the isolation of a new dimeric sesquiterpene lactone, ainsliadimer A (1). The structure of 1 was elucidated by spectroscopic analysis, and confirmed by single crystal X-ray diffraction. Ainsliadimer A represents an unusual carbon skeleton with a cyclopentane system connecting the two monomeric sesquiterpene lactone units. This unique molecule exerted potent inhibitory activity against the production of nitric oxide in RAW264.7 stimulated by LPS.

Three new alkaloids, named bufoserotonins A–C (1–3), were isolated from the traditional Chinese medicine ChanSu. Their structures were elucidated on the basis of spectroscopic analysis, especially of 2D-NMR data.

A novel and sensitive HPLC-UV method has been developed for the simultaneous determination of five major flavonoids in Hypericum japonicum hydroalcoholic extract. The chemical profile of five flavonoids, including taxfolin-7-O-alpha-L-rhamnoside (1), isoquercitrin (2), quercitrin (3), quercetin-7-O-alpha-L-rhamnoside (4) and quercetin (5) was acquired by using high-performance liquid chromatography-diode array detector coupled to an electrospray tandem mass spectrometer (HPLC-DAD-ESI/MS). The analysis was performed on a ZORBAX SB-C18 analytical column (5 microm, 250 mm x 4.6 mm, i.d.) with a gradient solvent system of acetonitrile-0.5% aqueous formic acid. The validation was carried out and the linearities (r(2)>0.9997) and recoveries (ranged from 98.4% to 99.8%) were acceptable. The limits of detection (LOD) of these flavonoids ranged from 0.5 to 7.5 ng. The results indicated that the contents of investigated flavonoids in H. japonicum varied significantly from habitat to habitat with contents ranging from 2.00 to 34.18 mg/g. The proposed method is simple, effective and suitable for the quality control of this traditional Chinese medicine (TCM).

1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.

Columbin is an important component isolated from Radix Tinosporae. It has been demonstrated to possess many pharmacological activities, including anti-inflammation, antitumor and inhibition of enzyme activity in vivo. The purpose of the present study was to examine in vivo pharmacokinetics and bioavailability of columbin in rats using a high-performance liquid chromatography coupled with tandem mass spectrometry quantitative detection method. The columbin was extracted from rat plasma samples by methyl tert-butyl ether, evaporated and reconstituted in 100 microL methanol prior to analysis. The separation was performed using a Luna reversed-phase analytical column (5 microm, 100 x 2.0 mm) and an SB-C18 guard column (5 microm, 20 x 4.0 mm). The mobile phase was a mixture of methanol and water containing 25 mmoL/L NH(4)Ac (80:20, v/v). The method was validated within the concentration range of 5-5000 ng/mL, and the calibration curves were linear with correlation coefficients (r) >0.999. It was further applied to assess pharmacokinetics and oral bioavailability of columbin after i.v. and oral administration to rats. The oral bioavailability of columbin was only 3.18%, which indicated that columbin had poor absorption or underwent extensive first-pass metabolism.