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Herein, 17 previously undescribed polyacetylenes and 9 known ones were isolated from Tridax procumbens L. Their structures were identified using spectroscopic techniques (NMR, UV, IR, MS and optical rotation), the modified Mosher method, electronic circular dichroism (ECD) data and ECD calculation. The cytotoxicity of polyacetylenes on six human tumour cell lines (K562, K562/ADR, AGS, MGC-803, SPC-A-1 and MDA-MB-231) was evaluated. (3S,10R)-tridaxin B (2a), (3S,10S)-tridaxin B (2b) and tridaxin F (8) demonstrated substantial cytotoxic effects against the K562 cell line, with half-maximal inhibitory concentration (IC 50 ) values of 2.62, 14.43 and 17.91 μM, respectively. Cell and nucleus morphology assessments and Western blot analysis confirmed that the cytotoxicity of the three polyacetylenes on K562 cells was mediated through a dose-dependent apoptosis pathway. Furthermore, (3S,10R)-tridaxin A (1a) and tridaxin G (9) exhibited considerable inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages, with IC 50 values of 15.92 and 20.35 μM, respectively. Further investigations revealed that 9 exerted anti-inflammatory activities by impeding the nuclear translocation of NF-κB and down-regulating the expression of pro-inflammatory factors, including those of iNOS, COX-2, IL-1β and IL-6, in a concentration-dependent manner. The study provides evidence that polyacetylenes from T. procumbens may serve as a potential source of anti-tumour or anti-inflammatory agents for treating related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human DNA topoisomerase I (Topo I) is an essential enzyme in regulating DNA supercoiling during transcription and replication, and it is an important therapeutic target for anti-tumor agents. Bidens pilosa L. is a medicinal herb that is used as a folk medicine for cancers in China. A new flavonoid ( 1 ) and a new polyacetylene ( 20 ), along with eighteen flavonoids ( 2 - 19 ) and nine polyacetylenes ( 21 - 29 ), were isolated and identified from the methanol extract of the whole plant of B. pilosa , and some of the compounds ( 4 , 5 , 6 and 7 ) exhibited potent cytotoxicity against a panel of five human cancer cell lines. The DNA relaxation assay revealed that some flavonoids and polyacetylenes exerted inhibitory activities on human DNA Topo I, among them compounds 1 , 2 , 5 , 6 , 7 , 8 , 15 , 19 , 20 , 22 , and 24 were the most active ones, with IC 50 values of 393.5, 328.98, 145.57, 239.27, 224.38, 189.84, 89.91, 47.5, 301.32, 178.03, and 218.27 μM, respectively. The structure-activity analysis of flavonoids was performed according to the results from the Topo I inhibition assay. The DNA content analysis revealed that 5 , 6 , and 7 potently arrested cell cycle at the G 1 /S and G 2 /M phases in human colon cancer cell DLD-1 depending on the concentration of the inhibitors. The levels of protein expression related to the G 1 /S and G 2 /M cell cycle checkpoints were in accordance with the results from the DNA content analysis. These findings suggest that flavonoids are one of the key active ingredients accounting for the anti-tumor effect of B. pilosa .

Covering: up to 2023Conjugated polyynes are natural compounds characterized by alternating single and triple carbon-carbon bonds, endowing them with distinct physicochemical traits and a range of biological activities. While traditionally sourced mainly from plants, recent investigations have revealed many compounds originating from bacterial strains. This review synthesizes current research on bacterial-derived conjugated polyynes, delving into their biosynthetic routes, underscoring the variety in their molecular structures, and examining their potential applications in biotechnology. Additionally, we outline future directions for metabolic and protein engineering to establish more robust and stable platforms for their production.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl β-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl β-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations. Antihepatoma assay suggested that compound 1 exhibited activity against HepG2, Huh7, and SK-Hep-1 cells with inhibitory ratios of 77.1%, 90.8%, and 73.1% at 200.0 μM, respectively., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nine polyacetylenes, including five new compounds named sadivaethynes E-I (1-5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1-5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4 + probability analysis. Among them, the absolute configuration of compound 1-2, 4-5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC 50 value of 11.66 μM against HEPG2., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Five new polyacetylene derivatives (1-5), cyclocodonlandiynosides A-E, and eight known analogues (6-13) were isolated and identified from the fruits of Cyclocodon lancifolius. Their structures were established via spectroscopic and chemical methods, including NMR, HRESIMS, enzymatic hydrolysis, Mo 2 (OAc) 4 -induced circular dichroism and sugar derivatization. Compound 1 contains a nitrogenous fragment, which was rarely found in C14 polyacetylenes. Compounds 3 and 4 are polyacetylene glucosides possessing novel aglycones. All the isolated polyacetylenes (except 12) were screened for their xanthine oxidase (XO) inhibitory activity. All the tested compounds, at the concentration of 62.5 μg/mL, showed XO inhibiting effects. Among them, 13 and 3 showed the most potent XO inhibitory activity with IC 50 values of 87.65 and 96.32 μM, compared to the positive control allopurinol with an IC 50 value of 19.25 μM., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The chemical investigation of the methanol extract of the whole plant of Gymnanthemum theophrastifolium (Schweinf. ex Oliv. & Hiern) H.Rob. (Asteraceae) led to the isolation of a new elemane-type sesquiterpene (1), a new acetonide derived polyacetylene (2) and a naturally occurring compound (3) from the plant kingdom along with sixteen known compounds (4-19). Their structures were elucidated by extensive NMR and MS analysis. This is the first report on the chemical constituents of G. theophrastifolium. Furthermore, compounds 12, 13, and 14 are reported for the first time from the family Asteraceae, while compound 9 is reported for the first time from the genus Gymnanthemum. Thus, the present results provide valuable insights to the chemophenetic knowledge of G. theophrastifolium, which is also discussed in this work., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Chemical investigation of the polypore fungus Fistulina hepatica resulted in the isolation of five compounds, including four new polyacetylenic fatty acid derivatives - isocinnatriacetin B (1), isocinnatriacetin A (2), cinna-triacetin C (3) and ethylcinnatriacetin A (4) together with one known polyacetylene fatty acid derivative - cinnatriacetin A (5). The structures were elucidated using spectroscopic methods (UV, NMR, HR-ESIMS) along with comparison to literature data. Antibacterial activity screening of compounds 1-5 against ESKAPE bacterial strains in vitro with zones of inhibition (ZOI) was performed and MIC values were established for the most active compounds (3 and 4). Together with that morphological and growth parameters under solid-phase cultivation were also researched.

A new polyacetylenic glucoside together with three known compounds were isolated from the whole herb of Bidens pilosa L. The structure elucidation of these four compounds was employed by combining NMR and HR-MS data as 4- O - β -D-glucopyranosyloxy-1-hydroxy- 6-( E )-tetradecene-8,10,12-triyne ( 1 ), 3- O - β -D-glucopyranosyloxy-1-hydroxy-6-( E )-tetradec- ene-8,10,12-triyne ( 2 ), 2- O - β -D-glucopyranosyloxy-1-hydroxy-5-( E) -tetradecene-7,9,11-triy- ne ( 3 ) and icthyothereol acetate ( 4 ). Additionally, bioactivity study showed that these compounds have potential anti-inflammatory activity. This study has certain guiding significance for the development and utilisation of polyacetylene compounds in Bidens pilosa L.

In this study, the anticholinesterase effects of the extracts and isolated compounds from the roots of endemic Prangos uechtritzii Boiss & Hausskn (Apiaceae) are reported. A novel polyacetylenic compound; (+)-8-O-methyloplopantriol A along with two known polyacetylenes; (-)-panaxynol, (+)-falcarindiol and fifteen known coumarin derivatives; umbelliferone, 6-formylumbelliferone, suberosin, 7-demethylsuberosin, (+)-ulopterol, tamarin, psoralen, imperatorin, (+)-oxypeucedanin, (+)-oxypeucedanin hydrate, (+)-oxypeucedanin methanolate, (+)-marmesin, (-)-prantschimgin, (+)-decursinol, and (-)-adicardin were isolated from the hexane (Pu-HE), chloroform (Pu-CE), and methanol (Pu-ME) extracts of P. uechtritzii roots. (-)-Panaxynol, (+)-falcarindiol, 6-formylumbelliferone, (+)-decursinol, and (-)-adicardin were obtained from the genus Prangos for the first time. (+)-8-O-Methyloplopantriol A inhibited both AChE (IC 50 =194.5±5.8 μM) and BChE (IC 50 =51.9±2.96 μM) enzymes. (+)-Falcarindiol, 6-formylumbelliferone, 7-demethylsuberosin, tamarin, and imperatorin also exhibited BChE-specific inhibitory activities (IC 50 =27.88-93.86 μM). (+)-Falcarindiol (IC 50 =27.88±0.91 μM) and imperatorin (IC 50 =30.89±1.40 μM) as the most active components could be led compounds to develop new BChE inhibitors with further research against Alzheimer's disease., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Although C 17 polyacetylenes from Panax ginseng exhibit cytotoxic properties against various tumor cells, there have been few experiments on epithelial ovarian carcinoma cells. This study aimed to investigate the cytotoxic effects of C 17 polyacetylenes from P. ginseng against ovarian cancer cell lines. Four unreported ( 1 - 4 ) and fifteen known ( 5 - 19 ) C 17 polyacetylenes were obtained from the roots of P . ginseng using repeated chromatography (open column, MPLC, and preparative HPLC). The chemical structures of all the compounds were determined by analyzing their spectroscopic data (NMR, IR, and optical rotation) and HR-MS. The structures of new polyacetylenes were elucidated as (3 S ,8 S ,9 R ,10 R )-(-)-heptadeca-9,10-epoxy-4,6-diyne-3,8-diyl diacetate ( 1 ), (3 S ,8 S ,9 R ,10 R )-(-)-heptadeca-1-en-9,10-epoxy-4,6-diyne-3,8-diyl diacetate ( 2 ), (-)-haptadeca-9,10-epoxy-8-methoxy-4,6-diyne-3,11-diol ( 3 ), and (3 R ,9 R ,10 R )-(+)-3-acetoxy-9,10-dihydroxyheptadeca-1-en-4,6-diyne ( 4 ), named ginsenoynes O, P, and Q, and 3-acetyl panaxytriol, respectively. Subsequently, in vitro experiments on A2780 and SKOV3 human epithelial ovarian carcinoma cells were performed to assess the cytotoxic properties of the isolates. Among the isolates, panaquinquecol 4 ( 15 ) exhibited the most remarkable cytotoxic effects on both human ovarian cancer cells A2780 (IC 50 value of 7.60 μM) and SKOV3 (IC 50 value of 27.53 μM). Therefore, C 17 polyacetylenes derived from P . ginseng may warrant further investigation for their therapeutic potential in epithelial ovarian cancer., Competing Interests: The authors declare no conflicts of interest.

Eight previously undescribed polyacetylenes, cirussurynes A-H, were isolated from the methanolic extract of the roots of Cirsium japonicum var. ussuriense. Their structures were elucidated by interpretation of extensive 1D and 2D NMR spectroscopy and HRESIMS spectrometry data. The configuration of triols in cirussurynes A, B, and E-G was deduced by the J-value based configuration analysis together with specific rotation values. All compounds were evaluated for their inhibitory effects on nitric oxide production against LPS-induced RAW 264.7 macrophages, and exhibited IC 50 values ranging from 5.5 to 68.7 μM., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The phytochemical investigation on Atractylodes chinensis afforded 15 polyacetylenes 1-15 and one meroterpenoid 16. Of the 16 isolates, compounds 4 and 9 are new ones, and compounds 8 and 16 are first reported from nature. In addition, the relative configuration of 1 and the available NMR data of compounds 1, 8, and 16 were first provided. Their structures were elucidated by extensive analysis of MS, UV, IR, and NMR spectroscopic data. Besides, all isolated compounds were evaluated for their effects on RANKL-induced osteoclastogenesis in BMMs. Among them, polyacetylenes 12-14 showed potent inhibitory activity with IC 50 values of 0.67 ± 0.05 μM, 0.72 ± 0.31 μM, and 2.40 ± 0.41 μM, respectively. The current work demonstrates the polyacetylenes are the main active constituents of A. chinensis against osteoclastogenesis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Polyacetylenes are a kind of small active compounds with carbon-carbon triple bond with vast occurrence in plants. Polyacetylenes have attracted considerable attention owing to their diverse biofunctions like tumor suppression, immunity regulation, depression resistance and neural protection. The present review intends to reconstruct data concerning the occurrence, pharmacology, toxicology and pharmacokinetics of polyacetylenes from herbal medicine in a systematic and integrated way, with a view to backing up their curative potential and healthcare properties (2014-2021). The natural polyacetylene-related data were all acquired from the scientific search engines and databases that are globally recognized, such as PubMed, Web of Science, Elsevier, Google Scholar, ResearchGate, SciFinder n and CNKI. A total of 183 polyacetylenes were summarized in this paper. Modern pharmacological studies indicated that polyacetylenes possess multiple biological activities including antitumor, immunomodulatory, neuroprotective, anti-depression, anti-obesity, hypoglycemic, antiviral, antibacterial, antifungal, hepatoprotective and renoprotective activities. As important bioactive components of herbal medicine, the pharmacological curative potential of polyacetylenes has been described against carcinomas, inflammatory responses, central nervous system, endocrine disorders and microbial infection in this review. While, further in-depth studies on the aspects of polyacetylenes for toxicity, pharmacokinetics, and molecular mechanisms are still limited, thereby intensive research and assessments should be performed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Four new polyacetylene substances, sadivaethynes A-D, were isolated from the ethanol extract of the roots of Saposhnikovia divaricata (Turcz.) Schischk using repeated column chromatography. Structural elucidation of compounds 1-4 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for cytotoxicity against two human cancer cell lines (MGC-803, Ishikawa) in vitro .

Three new polyacetylenes, pellynols P (1), Q (2), and R (3) were isolated from the marine sponge Petrosia sp., along with the known compound pellynol H (4). Their structures were determined by analyses of extensive NMR, HR-MS, and ESI-MS/MS data. All compounds displayed potent cytotoxicities against human hepatocellular carcinoma HepG2, human melanoma A375, and human colorectal carcinoma HT29 cell lines with IC 50 values at the range of 1.4-4.4 μM., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Bacterial polyynes are highly active natural products with a broad spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. By integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), in the biosynthesis gene cluster of antifungal polyynes (massilin A 1, massilin B 2, collimonin C 3, and collimonin D 4) of Massilia sp. YMA4. Crystallographic analysis indicated that bacterial polyynes serve as covalent inhibitors of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited the cell viability of Candida albicans by targeting ERG10, the homolog of MasL. Thus, this study demonstrated that acetyl-CoA acetyltransferase is a potential target for developing antifungal agents., (© 2022. The Author(s).)

Twenty-two sesquiterpenoids ( 1 - 22 ) and 11 polyacetylenes ( 23 - 33 ) were obtained from the rhizomes of Atractylodes lancea . Among them, 11 compounds ( 1 - 5 , 11 , 12 , 23 , 24 , 30 , and 31 ) are new. The scaffolds represented by the isolates of sesquiterpenoids were found to be varied and included two rare rearranged spirovetivane sesquiterpenoids with a spiro [4,4] skeleton, eight spirovetivanes, three guaianes, eight eudesmanes, and one eremophilane. Their planar structures and relative configurations were elucidated by UV, IR, 1D and 2D NMR, and HRESIMS data analysis. The absolute configurations of the new sesquiterpenoids were determined using X-ray diffraction analysis and by comparison of the calculated and experimental electronic circular dichroism and optical rotation data, as well as chemical transformations. All the isolated compounds ( 1 - 33 ) were evaluated for their activity against RANKL-induced osteoclastogenesis in bone marrow macrophages. Two polyacetylene-type compounds, 25 and 32 , showed potent activity with IC 50 values of 1.3 and 0.64 μM, respectively. Rearranged spirovetivane sesquiterpenoids with a spiro [4,4] skeleton are reported herein from the genus Atractylodes for the first time. Polyacetylenes were demonstrated as the main active constituents of A. lancea with osteoclastogenesis inhibitory activity.

Three new polyacetylenes (1-3), together with six known polyacetylenes (4-9), were isolated from a 95% aqueous ethanol extract of the Atractylodes japonica Koidz.ez Kitam. Their structures were elucidated by HR-ESI -MS and NMR techniques as well as comparison with those reported in literatures. The cytotoxic activity of 1 - 3 were also evaluated.

A new polyacetylene, namely isolobetyol ( 1 ), was isolated from the root of Platycodon grandiflorum (Jacq.) A. DC., together with lobetyol ( 2 ), lobetyolin ( 3 ), and trans -2-hexenyl β-D-glucoside ( 4 ). The structures of the isolated natural products were identified by high-resolution mass spectrometric (HR-MS) and nuclear magnetic resonance (NMR) spectroscopic analyses. The obtained spectroscopic data was in good agreement with the data previously reported in the literature. The anti-proliferative effects of the isolated compounds were examined using the PC-3 prostate cancer cell line. Compounds 1 - 3 considerably reduced the proliferation of the PC-3 cells with IC 50 values of 6.76, 12.72, and 5.73 μM, respectively.

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4 ), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5 ), GLS1 , GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

Choushenpilosulynes D-G ( 1-4 ): four new polyynes were isolated from the roots of Codonopsis pilosula (Campanulaceae) cultivated in Yunnan province, China. Their structures were identified by spectroscopic methods. Bioactive evaluation showed that choushenpilosulynes E ( 2 ) and F ( 3 ) demonstrated potent inhibitory effect on lipid formation induced by 100 μM oleic acid stimulation. In addition, choushenpilosulyne F ( 3 ) uncovered inhibitory activity against the expression of human 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) gene transcript in HepG2 cells.

Lobetyolin (LBT), a general marker compound mainly found in Codonopsis plants including C. pilosula , C. tubulosa , and C. lanceolata , exhibits antitumor, antiviral, anti-inflammatory, mucosal protective, and antioxidant activities. Xanthine oxidase (XO) catalyzes the formation of uric acid from xanthine, a critical metabolic pathway related to hyperuricemia and gout. The aim of this study was to investigate the effect of LBT on XO activity and its mechanism using in vitro enzyme assay system and in vivo potassium oxonate-induced hyperuricemic mice. LBT was found to weakly inhibit XO activity via a mixed type mechanism. Consistently, the impact of 1-week oral LBT treatment on serum XO activity in vivo is limited in hyperuricemic mice. However, oral LBT at 50 mg/kg significantly reduced hepatic XO activity in vivo . To the best of our knowledge, this is the first study to report effects of LBT on XO activity and its inhibition mechanism.

Fruiting body-forming members of the Basidiomycota maintain their ecological fitness against various antagonists like ascomycetous mycoparasites. To achieve that, they produce myriads of bioactive compounds, some of which are now being used as agrochemicals or pharmaceutical lead structures. Here, we screened ethyl acetate crude extracts from cultures of thirty-five mushroom species for antifungal bioactivity, for their effect on the ascomycete Saccharomyces cerevisiae and the basidiomycete Ustilago maydis . One extract that inhibited the growth of S. cerevisiae much stronger than that of U. maydis was further analyzed. For bioactive compound identification, we performed bioactivity-guided HPLC/MS fractionation. Fractions showing inhibition against S. cerevisiae but reduced activity against U. maydis were further analyzed. NMR-based structure elucidation from one such fraction revealed the polyyne we named feldin, which displays prominent antifungal bioactivity. Future studies with additional mushroom-derived eukaryotic toxic compounds or antifungals will show whether U. maydis could be used as a suitable host to shortcut an otherwise laborious production of such mushroom compounds, as could recently be shown for heterologous sesquiterpene production in U. maydis .

A new bisepoxylignan dendranlignan A (A1) and the known compound lantibeside D (D2) was isolated from Chrysanthemum Flower, the dried capitulum of Dendranthema morifolium (Ramat.) kitam. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-NMR, 2D-NMR and MS data. Additionally, A1 and D2 were evaluated for their effects on the production of inflammatory mediators in H9c2 cardiomyocytes stimulated with lipopolysaccharide (LPS). Results demonstrated that A1 and D2 decreased LPS-induced production of inflammatory cytokines TNF-α, IL-2 and IFN-γ in H9c2 cells. Both compounds also decreased the nuclear localization of c-JUN, p-P65 and p-IRF3, but did not affect the level of TLR4. Molecular docking indicated that A1 and D2 occupied the ligand binding sites of TLR4-MD2. In the present study, we for the first time discovered a new bisepoxylignan compound A1, and found that this compound has a potential to inhibit inflammation by inhibiting TLR4 signaling., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Oplopanax horridus and Panax ginseng are members of the plant family Araliaceae, which is rich in structurally diverse polyacetylenes. In this work, we isolated and determined structures of 23 aliphatic C 17 and C 18 polyacetylenes, of which five are new compounds. Polyacetylenes have a suitable scaffold for binding to PPARγ, a ligand-activated transcription factor involved in metabolic regulation. Using a reporter gene assay, their potential was investigated to activate PPARγ. The majority of the polyacetylenes showed at least some PPARγ activity, among which oplopantriol B 18-acetate ( 1 ) and oplopantriol B ( 2 ) were the most potent partial PPARγ activators. By employing in silico molecular docking and comparing the activities of structural analogues, features are described that are involved in PPARγ activation, as well as in cytotoxicity. It was found that the type of C-1 to C-2 bond, the polarity of the terminal alkyl chain, and the backbone flexibility can impact bioactivity of polyacetylenes, while diol structures with a C-1 to C-2 double bond showed enhanced cytotoxicity. Since PPARγ activators have antidiabetic and anti-inflammatory properties, the present results may help explain some of the beneficial effects observed in the traditional use of O. horridus extracts. Additionally, they might guide the polyacetylene-based design of future PPARγ partial agonists.

Phytochemical investigation on the leaves and twigs of Toona ciliata has led to the isolation of four new polyynes ( 1 - 4 ) and two knowns ( 5 and 6 ). Their structures were determined by extensive spectroscopic analysis (MS, UV, IR, and NMR) and Mosher's method. All compounds were evaluated for their inhibitory activities against HepG2 human tumor cell line but were inactive.

Using activity guided purification, four known compounds, sesquiterpene atractylenolide III (1), and the polyacetylenes 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-1-ol (2), 14-acetoxy-12-α-methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol (3), and 14-acetoxy-12-β -methylbutyl-2E,8E,10E-trien-4,6-diyn-1-ol (4), were isolated from a traditional herbal medicine, Atractylodes rhizome. Structurally similar 3 and 4 (3/4 mixture) were obtained as a mixture. In intact Chinese hamster ovary (CHO) K1 cell assays, 1, 2, and a 3/4 mixture selectively inhibited cholesterol [ 14 C]oleate synthesis from [ 14 C]oleate with IC 50 values of 73.5 µM, 35.4 µM, and 10.2 µM, respectively, without any effects on cytotoxicity. As a potential target of these inhibitors involved in cholesteryl ester (CE) synthesis, effects on sterol O-acyltransferase (SOAT) activity were investigated using microsomes prepared from CHO-K1 cells as an enzyme source. Hence, these compounds inhibit SOAT activity with IC 50 values (211 µM for 1, 29.0 µM for 2, and 11.8 µM for 3/4 mixture) that correlate well with those measured from intact cell assays. Our results strongly suggest that these compounds inhibit CE synthesis by blocking SOAT activity in CHO-K1 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The purpose of the present study was to evaluate the anti-cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT-116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin-α. The levels of glutamine, glutamic acid, α-ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V-FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT-qPCR, Western blot and immunofluorescence staining. The expressions of cleaved-caspase-3, caspase-3, cleaved-caspase-7, caspase-7, cleaved-PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT-116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine-related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT-116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin-α promoted the inhibitory effect of Lobetyolin on ASCT2-mediated apoptosis. Lobetyolin also exerted anti-cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2-mediated glutamine metabolism, which was possibly governed by p53., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The total syntheses of all stereoisomers of notoincisol A, a recently isolated natural product with potential anti-inflammatory activity, are reported. The asymmetric synthesis was conducted employing a lipase-mediated kinetic resolution, which enables easy access to all required chiral building blocks with the aim of establishing the absolute configuration of the naturally occurring isomer. This was achieved by comparison of optical properties of the isolated compound with the synthetic derivatives obtained. Moreover, an assessment of the biological activity on PPARγ (peroxisome proliferator-activated receptor gamma) as a prominent receptor related to inflammation is reported. Only the natural isomer was found to activate the PPARγ receptor, and this phenomenon could be explained based on molecular docking studies. In addition, the pharmacological profiles of the isomers were determined using the GABA A (gamma-aminobutyric acid A) ion channel receptor as a representative target for allosteric modulation related to diverse CNS activities. These compounds were found to be weak allosteric modulators of the α1β3 and α1β2γ2 receptor subtypes.

The first chemical study of the marine sponge Callyspongia cf. californica widely distributed along the coasts of the Tropical Eastern Pacific led to the identification of a new family of amphiphilic derivatives called callyspongidic acids. The four isolated metabolites 1-4 feature a hydrophilic diacid end opposed to both an aromatic moiety and a long alkyl chain. They were evaluated against a panel of pathogenic microbes and seven tumoral cell lines, displaying moderate inhibitory properties against the A2058 melanoma cell line with an IC 50 of 3.2 μM for callyspongidic acid C13:0 (2).

Phytochemical investigation of the apolar extract obtained from aerial parts of the Iranian endemic plant Echinophora platyloba DC (Apiaceae) resulted in the characterization of the polyacetylene fraction of this plant. This resulted to be composed of the known echinophorins A and B, embedding the very rare α-pyrone terminal, and of the new echinophorin D ( 3 ), including also three conjugated triple bonds. The chemical structures of these compounds were secured by detailed inspection of MS and 1D/2D NMR spectra. The isolated polyacteylenes were evaluated for their modulation of six thermo-TRP channels and they revealed a selective activity on TRPA1, an ion channel involved in the mediation of neuropathic and inflammatory pain. This is the first report on the activity of plant polyacetylenes on transient receptor potential (TRP) channels.

Three new polyynes, named choushenpilosulynes A-C ( 1 - 3 ), were isolated from an 85% aqueous EtOH extract of the roots of Codonopsis pilosula cultivated in Xundian County of Yunnan province, China. Their structures, including the absolute configuration of the glucose residue in 1 and 2 , were determined by spectroscopic analysis and gas chromatography (GC). In addition, biological evaluation shows that all the compounds can inhibit the expression of the squalene monooxygenase (SQLE) gene in HepG2 cells, suggesting that these compounds may be involved in lipid metabolism., Competing Interests: The authors declare that there is no conflict of interest.

The knowledge about the activity of polyacetylenes was extended by their new acetylcholinesterase inhibition and antibacterial activity against plant pathogenic bacteria. For this discovery, an utmost streamlined workflow, which we consider to be of high potential in the field of natural product or superfood search was developed. It demonstrates the combined power of biological, biochemical and chemical fingerprints. Bioactive components of tansy (Tanacetum vulgare L.) root extract were profiled and identified by high-performance thin-layer chromatography hyphenated with in situ effect-directed analysis, chemical derivatizations and high-resolution mass spectrometry (HPTLC-UV/Vis/FLD-EDA-HRMS). The effect-directed profiling was performed using four bacterial bioassays including two plant pathogens, an antioxidant assay and acetyl- and butyrylcholinesterase inhibitory assays. The chromatographic, spectral and powerful mass spectrometric study of zones that exerted substantial antibacterial and/or antioxidant and/or acetylcholinesterase inhibitory effects allowed these multi-potent zones to be identified as polyacetylenes. Five polyacetylene compounds were assigned to be 2-non-1-ene-3,5,7-triynyl-3-vinyl-oxirane, 2-(2,4-hexadiynylidene)-3,4-epoxy-1,6-dioxaspiro[4.5]decane, trans- and cis-2-(2,4-hexadiynylidene)-1,6-dioxaspiro[4.5]dec-3-ene and tetradeca-2,4,6-triine-8-en-12-one. This study clearly showed the advantage of the combined use of different ionization sources, i.e. electrospray ionization via an elution-head based interface and also the Direct Analysis in Real Time interface, for HRMS analysis of compounds from the same class with very similar chromatographic behavior and polarity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Classical synthetic approaches to highly unsaturated polyene/yne natural products rely on iterative cross-coupling of linear fragments. Herein, we present an expeditious and unified approach to the unsaturated backbone of polyacetylenes via domino cuprate addition/4π-electrocyclic ring opening of a stereodefined cyclobutene intermediate. This sets the stage for a detailed biological assessment of the role of Virol A and Cicutoxin as inhibitors of GABA induced chloride currents, providing further insight into the interaction of these highly potent toxins towards the GABA A receptor, including the structure-activity relationship of the derivatives.

Background and Methods: Oplopanax elatus (Nakai) Nakai is used in folk medicine in China. In this study, the antiproliferative activity of an O. elatus fraction extracted by ethyl acetate (EF) was tested on human breast cancer MCF-7 cells, human colon cancer HCT-116 cells, and human stomach cancer AGS cells. The potential mechanism of antiproliferation was also investigated using an apoptosis assay., Results: The results showed that the EF remarkably suppressed proliferation of human breast, stomach, and colon cancer cells. Further apoptosis tests by flow cytometry and immunoblot analyses showed the EF inhibited HCT-116 cell proliferation by inducing apoptosis. The bioassay-monitored fractionation of the EF resulted in the isolation of two polyacetylenes, falcarindiol (compound 1) and oplopandiol (compound 2), with falcarindiol possessing the strongest antiproliferative activity in colon cancer cells., Conclusion: Together, this study evaluated the anticancer activity of an O. elatus extract against human cancer cells, and provided the basis for further development of this herbal extract for the treatment of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

New targeted therapies are urgently needed to improve the survival of patients with refractory osteosarcoma (OS). In this study, we show that bortezomib (BTZ), not for OS treatment in the clinic, induces endoplasmic reticulum (ER) stress in U-2 OS cells. Loss of GRP78 sensitizes OS to BTZ with concomitant upregulation of ATF4 and CHOP, which indicates excessive protein synthesis. The relevance of these findings is confirmed in vivo as shown by GRP78 knockdown that delays the growth of U-2 OS xenografts in the presence of BTZ. Here, we demonstrate that MG7, a natural polyyne, can trigger apoptosis. Of note, the apoptotic response to MG7 is dependent on ATF4 but not on the upstream PERK signaling pathway. Interestingly, MG7-induced ATF4 expression does not result in an increase in the levels of CHOP. We demonstrate for the first time that GRP78 physically interacts with the N-terminal domain of CHOP to accelerate its ubiquitination in a p300-dependent manner, which in turn desensitize the tumors to ER stress. Overall, inhibiting GRP78 to strengthen the molecular mechanism of ATF4 via stabilizing CHOP protein may provide a potential vulnerability in OS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The genus Echinacea (Asteraceae) includes species traditionally used in phytotherapy. Among them, Echinacea pallida (Nutt.) Nutt. root extracts are characterized by a representative antiproliferative activity, due to the presence of acetylenic compounds. In this study, supercritical fluid extraction (SFE) was applied and compared with conventional Soxhlet extraction (SE) in order to obtain a bioactive extract highly rich in polyacetylenes and polyenes from E. pallida roots. The composition of the extracts was monitored by means of HPLC-UV/DAD and HPLC-ESI-MS n by using an Ascentis Express C 18 column (150mm×3.0mm I.D., 2.7μm, Supelco, Bellefonte, PA, USA) with a mobile phase composed of (A) water and (B) acetonitrile, under gradient elution. By keeping SFE time at the threshold of 1h (15min static and 45min dynamic for 1 cycle) with the oven temperature set at 40-45°C and 90bar of pressure, an overall extraction yield of 1.18-1.21% (w/w) was obtained, with a high selectivity for not oxidized lipophilic compounds. The biological activity of the extracts was evaluated against human non-small lung A549 and breast carcinoma MCF-7 cancer cell lines. The cytotoxic effect of the SFE extract was more pronounced towards the MCF-7 than the A549 cancer cells, with IC 50 values ranging from 21.01±2.89 to 31.11±2.l4μg/mL; cell viability was affected mainly between 24 and 48h of exposure. The results show the possibility of a new "green" approach to obtain extracts highly rich in genuine polyacetylenes and polyenes from E. pallida roots. The bioactivity evaluation confirmed the cytotoxicity of E. pallida extracts against the considered cancer cell lines, especially against MCF-7 cells, thus suggesting to represent a valuable tool for applicative purposes in cancer prevention., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Echinophora cinerea aerial parts are used in folk medicine to cure gastric diseases and as a food seasoning in cheese and yogurt. Besides several pharmacological effects have been assigned to Echinophora spp., there is no phytochemical investigation on this genus other than our previous publication on flavonoids. An acetone extract of E. cinerea afforded three new (1-3) polyacetylenes, one rare monoterpenoid glycoside as verbenone-5-O-β-D-glycopyranoside (4) and one prenylated coumarin as osthol (5). The structures of all new compounds were elucidated using modern spectroscopic methods, including 2D NMR and mass analyses. The potency of the compounds to induce cell death was determined on SKNMC, PC3 and MCF-7 cell lines using MTT method in which compounds 1 and 2 showed moderate cytotoxic effects, especially against PC3 cells.

Ongoing consumer concerns over using synthetic additives in foods has strongly influenced efforts worldwide to source suitable natural alternatives. In this study, the antibacterial efficacy of polyacetylene and glucosinolate compounds was evaluated against both Gram positive and Gram negative bacterial strains. Falcarinol [minimum inhibitory concentration (MIC) = 18.8-37.6 μg/mL] demonstrated the best overall antibacterial activity, while sinigrin (MIC = 46.9-62.5 μg/mL) was the most active glucosinolate compound. High-performance liquid chromatography with a diode array detector analysis showed falcarinol [85.13-244.85 μg/g of dry weight (DW)] to be the most abundant polyacetylene within six of the eight carrot (Daucus carota) cultivars investigated. Meanwhile, sinigrin (100.2-244.3 μg/g of DW) was the most abundant glucosinolate present within the majority of broccoli (Brassica oleracea) cultivars investigated using ultra performance liquid chromatography-tandem mass spectrometry analysis. The high abundance of both falcarinol and sinigrin within these respective species suggests that they could serve as potential sources of natural antibacterial agents for use as such in food products.

Two new polyhydroxy polyacetylenes, herpecaudenes A and B (1 and 2), were isolated from the ethanol extract of fruits of Herpetospermum caudigerum, an important Tibetan medicine. The structures of them were elucidated on the basis of extensive spectroscopic methods including UV, IR, HRESIMS, 1 H and 13 C NMR, HMBC, HSQC, and 1 H- 1 H COSY. Compound 2 showed significant inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages with IC 50 values of 7.05 ± 1.59 µM.

A new brominated polyacetylene, xestonariene I (1), along with three known related analogues (2-4), was obtained from Chinese marine sponge Xestospongia testudinaria. Its structure was determined on the basis of detailed spectroscopic analysis and by comparison with literature data. Compound 4 exhibited significant inhibitory activity against pancreatic lipase, which plays a key role in preventing obesity, with an IC 50 value of 0.61 μM, being comparable to that of the positive control orlistat (IC 50  = 0.78 μM).

Panax ginseng has been studied for its chemo-preventive properties and pharmaceutical potential. Polyacetylenic compounds isolated from Panax ginseng root typically comprised of non-polar C 17 compound have been reported to exhibit bioactive properties. The objective of this project is to extract, isolate, and characterize bioactive polyacetylenes from Panax ginseng root using various extraction and separation methods Ginseng was extracted by reflux using methanol, ethanol, hexane, ethyl acetate, methanolic ultrasonication. The extracts were partitioned with hexane to obtain water-soluble portion and hexane-soluble portion. Hexane was subsequently removed under vacuum, and formed a crude polyacetylenes extract (crude PA). Silica gel chromatography and semi-preparative HPLC were utilized to prepare 5 fractions and the polyacetylenes were measure by HPLC and molecular weights confirm my APCI-MS and MNR. The bioactive effect was measured by MTT viability assay using murine 3T3-L1 cells. Extraction with methanol under reflux produced significantly larger amount of polyacetylenes (p<0.05). Liquid-liquid extraction and column chromatography were used to separate polyacetylenic compounds into five different fractions. Major polyacetylenes, panaxynol and panaxydol were found in fraction 1 and 2 respectively. Dose-response relationships were observed in 3T3-L1 cells and LC50 were 13.52±3.05μg/mL (fraction 1), 3.69±1.09μg/mL (fraction 2), 52.88±11.16μg/mL (fraction 3), 85.91±27.37μg/mL (fraction 4) and 135.52±32.91μg/mL (fraction 5). Fraction 2 containing panaxydol was found to have exhibited the greatest anti-proliferative effects on 3T3-L1 preadipocytes. Extraction with methanol under reflux produced significantly more polyacetylenes. Fractions that contain panaxydol was the most cytotoxic., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polyacetylene glycosides, (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-β-D-glucopyranoside (trivially named coreoside E) and (6Z, 12E)-tetradecadiene-8,10-diyne-1-ol-3(R)-O-β-L-arabinopyranosyl-(1 → 2)-β-D-glucopyranoside (trivially named coreoside F), were isolated from buds of Coreopsis tinctoria Nutt., together with one known compound, coreoside B. Their chemical structures were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivities. Coreoside E exhibited high levels of antimicrobial activity against Staphylococcus aureus and Bacillus anthracis with minimum inhibitory concentrations of 27 ± 0.27 and 18 ± 0.40 μM, respectively, whereas coreoside F and coreoside B showed weak antimicrobial activity against S. aureus and B. anthracis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

An ongoing phytochemical investigation of the rhizomes of Atractylodes lancea resulted in the isolation of four new C 10 -type polyacetylene glycosides (1-4). Their structures were elucidated on the basis of extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of compounds 2-4 were determined by comparing the specific rotations of their aglycones. Notably, compounds 2 and 3 exhibited significant hepatoprotective activities against APAP-induced HepG2 cell injury at a concentration of 10 μM. Compounds 2 and 3 showed weak anti-inflammatory effects on LPS-induced NO production in microglia BV2 cells at a concentration of 10 μM.

In this work, we report a protocol for synthesizing nanosize ovalbumin-functionalized polydiacetylene (PDA) liposomes (LP-Ova). We show that LP-Ova administered per-orally (p.o.) and subcutaneously (s.c.), without the use of adjuvants, induces high serum IgG1 titers. As reported previously using polystyrene nanoparticles (NPs), p.o.-primed mice developed high titers of IgG2c and intestinal IgA following s.c. boosting immunization with LP-Ova. Mice that received a single s.c. immunization with LP-Ova did not develop serum IgG2c or intestinal IgA antibodies. Additionally, in s.c.-immunized mice serum IgG1 titers decreased significantly by 3 months after immunization. In contrast, in mice primed p.o. and boosted s.c. with LP-Ova, serum IgG1/IgG2c, and intestinal IgA antibody titers remained stable. Administration of LPs exerted no adverse effects on immunized mice as no morbidity or signs of toxicity were observed for the duration of the studies. These results indicate that antigen-conjugated liposomes are immunogenic and confirm a previous report that mucosal priming followed by a s.c. boosting immunization is the most effective strategy for inducing long-lasting mucosal IgA, as well as a polarized Th1/Th2 systemic response. In addition to being biodegradable and easily functionalized by conjugation, liposomes have a hollow core which can also be loaded with cargo, allowing for a targeted delivery of multiple antigens (or drugs) simultaneously. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 557-565, 2017., (© 2016 Wiley Periodicals, Inc.)

Neurotrophins play an important role in the control of the hair growth cycle. Therefore, neurotrophin receptor antagonists have therapeutic potential for the treatment of hair growth disorders. In this study, we investigated the inhibitory effect of Panax ginseng, a medicinal plant commonly used to treat alopecia, on the binding of neurotrophins to their receptors. In addition, we isolated and characterized the bioactive compounds of P. ginseng extracts. P. ginseng hexane extracts strongly inhibited brain-derived neurotrophic factor (BDNF)-TrkB and β-nerve growth factor (β-NGF)-p75 neurotrophin receptor (p75NTR) binding. Furthermore, we identified the following 6 polyacetylene compounds as the bioactive components in P. ginseng hexane extract: panaxynol (1), panaxydol (2), panaxydol chlorohydrin (3), 1,8-heptadecadiene-4,6-diyne-3,10-diol (4), panaxytriol (5), and dihydropanaxacol (6). In particular, compounds 4, 5, and 6 significantly inhibited BDNF-TrkB binding in a dose-dependent manner. To identify the structural component mediating the inhibitory effect, we investigated the effects of the hydroxyl moiety in these compounds. We found that the inhibitory effect of panaxytriol (5) was strong, whereas the inhibitory effect of Ac-panaxytriol (7) was relatively weak. Our findings suggest that P. ginseng-derived polyacetylenes with a hydroxyl moiety might provide therapeutic benefits to patients with hair growth disorders such as alopecia by inhibiting the binding of neurotrophins to their receptors. Although saponins have been proposed to be the primary mediators of the effects of P. ginseng on hair growth, this study revealed that polyacetylene compounds exert similar effects.

Three new polyacetylenic oleanane-type triterpenoids, baisanqisaponins A-C (1-3), and one new oleanane-type triterpenoid, chikusetsusaponin-V ethyl ester (4), together with 19 known compounds (5-23), were isolated from the roots of Panax japonicus. The structures were elucidated on the basis of spectroscopic analyses and chemical methods. Compounds 1-3 feature a rare panaxytriol group containing a polyacetylene on the saponin skeleton. Neuroprotective activity was evaluated for compounds 1-17, and angiotensin II-induced vascular smooth muscle cell proliferation inhibition was tested for compounds 5-7 and 10-12.

Ethnopharmacological Relevance: The genus Bupleurum includes approximately 200 species that are widely distributed in the Northern Hemisphere, Eurasia and North Africa. Certain species of this genus have long been used as antiphlogistic, antipyretic and analgesic agents in traditional folk medicine. As described in the Chinese Pharmacopoeia, the roots of Bupleurum chinense DC. and B. scorzonerifolium Willd. are the herbal materials that compose Chaihu (Radix Bupleuri), a well-known TCM herb., Aim of the Review: This review aims to provide up-to-date and comprehensive information regarding the distribution, toxicity, molecular mechanism and relatively new methods for the qualitative and quantitative determination of polyacetylenes in different Bupleurum species., Method: The information needed for this paper were sourced from publishing sites such as Elsevier, science Direct, PubMed; electronic search engines such as Scopus and Web of Science, Google scholar; other scientific database sites for chemicals such as ChemSpider, PubChem, SciFinder, and also from on line books., Results: Polyacetylenes, which are widely distributed in genus Bupleurum of the Apiaceae family, have high toxicity. Among polyacetylenes, bupleurotoxin, acetylbupleurotoxin and oenanthotoxin have strong neurotoxicity. Through previous research, it was found that the toxicity of Bupleurum polyacetylenes manifested as epileptic seizures, with the target of toxicity being the brain. The neurotoxicity of polyacetylenes exhibits a relationship with the γ-aminobutyric acid (GABA) receptor pathway, and polyacetylenes have been shown to inhibit GABA-induced currents (I GABA ) in a competitive manner., Conclusions: The plants of genus Bupleurum have been used in traditional medicine for thousands of years. However, certain species of this genus are poisonous, and it was attributed to the high content of polyacetylenes. The present review indicates that certain polyacetylenes in the genus Bupleurum have highly neurotoxic effects. The major challenge with regard to toxic polyacetylenes is to test their neurotoxic effects in vivo as well as in further preclinical studies, which will require large amounts of purified polyacetylenes. More reference substances should be prepared, and sophisticated analytical technologies should be developed to comprehensively assess the quality of Radix Bupleuri herbs. These investigations will be helpful for further utilization of the plants of genus Bupleurum., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Myeloid-derived suppressor cells (MDSCs) are implicated in the promotion of tumor metastasis by protecting metastatic cancerous cells from immune surveillance and have thus been suggested as novel targets for cancer therapy. We demonstrate here that oral feeding with polyacetylenic glycosides (BP-E-F1) from the medicinal plant Bidens pilosa effectively suppresses tumor metastasis and inhibits tumor-induced accumulation of granulocytic (g) MDSCs, but does not result in body weight loss in a mouse mammary tumor-resection model. BP-E-F1 is further demonstrated to exert its anti-metastasis activity through inhibiting the differentiation and function of gMDSCs. Pharmacokinetic and mechanistic studies reveal that BP-E-F1 suppresses the differentiation of gMDSCs via the inhibition of a tumor-derived, G-CSF-induced signaling pathway in bone marrow cells of test mice. Taken together, our findings suggest that specific plant polyacetylenic glycosides that target gMDSC differentiation by communicating with bone marrow cells may hence be seriously considered for potential application as botanical drugs against metastatic cancers.