Polyacetylene Glycosides Research Articles

Lobetyolin Suppresses the Proliferation of Hepatocellular Carcinoma through Activating DUSP1-ERK1/2 Signaling Pathway.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with limited treatment options. Lobetyolin (LBT), a polyacetylene glycoside mainly extracted from the roots of Codonopsis pilosula, has been reported to have anti-tumor efficancy in various cancers. However, the role of LBT as well as its underlying mechanisms in HCC remain unclear. Here we investigated the impact of LBT on the phenotype in HepG2 and Huh7 cells. We found that LBT significantly induced cell growth inhibition and mitochondria-dependent apoptosis in HCC cells. Moreover, LBT upregulated dual specificity phosphatase-1 (DUSP1) expression and knockingdown DUSP1 markedly attenuated those effects induce by LBT. Meanwhile, LBT decreased the phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), a well-recognized downstream effector of DUSP1, and knockingdown DUSP1 partially recovered LBT-induced inactivation of ERK1/2. In conclusion, the present study indicated that LBT could induce cell death of HCC via promotion of DUSP1-mediated ERK1/2 inhibition. These data will help to establish the evidence of LBT to treat HCC.

Research on the Mechanism of Growth of Codonopsis pilosula (Franch.) Nannf. Root Responding to Phenolic Stress Induced by Benzoic Acid.

Soil autotoxic chemosensory substances have emerged as the predominant environmental factors constraining the growth, quality, and yield of Codonopsis pilosula in recent years. Among a vast array of chemosensory substances, benzoic acid constitutes the principal chemosensory substance in the successive cultivation of C. pilosula. However, the exploration regarding the stress exerted by benzoic acid on the growth and development of C. pilosula remains indistinct, and there is a scarcity of research on the mechanism of lobetyolin synthesis in C. pilosula. In the current research, it was discovered that exposure to benzoic acid at a concentration of 200 mmol/L conspicuously attenuated the plant height, root length, total length, fresh weight, root weight, root thickness, chlorophyll content, electrolyte osmolality, leaf intercellular CO2 concentration (Ci), net photosynthesis rate (Pn), transpiration rate (Tr), and leaf stomatal conductance (Gs) of C. pilosula. Benzoic acid (200 mmol/L) significantly enhanced the activity of root enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA), and peroxidase (POD), as well as the accumulation of polysaccharides and lobetyolins (polyacetylene glycosides) in the roots of C. pilosula. In this study, 58,563 genes were assembled, and 7946 differentially expressed genes were discovered, including 4068 upregulated genes and 3878 downregulated genes. The outcomes of the histological examination demonstrated that benzoic acid stress augmented the upregulation of genes encoding key enzymes implicated in the citric acid cycle, fatty acid metabolism, as well as starch and sucrose metabolic pathways. The results of this investigation indicated that a moderate amount of benzoic acid could enhance the content of lobetyolin in C. pilosula and upregulate the expression of key coding genes within the signaling cascade to improve the resilience of C. pilosula lobetyolin against benzoic acid stress; this furnished a novel perspective for the study of C. pilosula lobetyolin as a potential substance for alleviating benzoic acid-induced stress.

HPLC-PDA Analysis of Polyacetylene Glucosides from Launaea capitata and Their Antibacterial and Antibiofilm Properties against Klebsiella pneumoniae.

Background/Objectives: Bacterial resistance and virulence are challenges in treating bacterial infections, especially in Klebsiella pneumoniae. Plants of the Launaea Cass. genus are used traditionally to address a variety of diseases, including infections, but the potential bioactive compounds are unknown. Our goals were to verify the potential contribution of two major polyacetylene glycosides isolated from our previous study, (3S,6E,12E)-6,12-tetradecadiene-8,10-diyne-1-ol 3-O-β-D-glucopyranoside (1) and bidensyneoside A (syn. gymnasterkoreaside A) [(3R,8E)-3-hydroxy-8-decene-4,6-diyn-1-yl β-D-glucopyranoside] (2), to the anti-infective properties of Launaea capitata and to develop a dependable HPLC method for their quantification; Methods: On a panel of K. pneumoniae clinical isolates, the antibacterial action of 1, 2, and the methanol extract of the whole L. capitata plant were evaluated by broth microdilution assay, while their antibiofilm action was evaluated by the crystal violet assay. qRT-PCR investigated luxS, mrkA, wzm, and wbbm genes that encode biofilm formation and quorum sensing (QS). The antibacterial activity of 1 was revealed by employing mice infection. Chromatographic separation was conducted using isocratic elution on a Hypersil BDS C18 column using a photodiode array (PDA) detector; Results: Compound 1 showed antibacterial activity with MIC values of 16-128 µg/mL. It remarkably reduced strong and moderate biofilm-forming bacterial isolates from 84.21% to 42.1% compared with the extract (68.42%) and 2 (78.95%). Compound 1 also downregulated the QS genes, luxS, mrkA, wzm, and wbbm, and exhibited in vivo antibacterial action through the enhancement of the histological construction of the liver and spleen, decreased TNF-α immunoreaction, bacterial burden, and the inflammatory mediators IL-1β and IL-6. A successful HPLC-PDA approach was developed to separate the binary mixture of 1 and 2 in less than 10 min with high sensitivity, with detection limits down to 0.518 and 0.095 µg/mL for 1 and 2, respectively; Conclusions: Compound 1 exhibited remarkable antibacterial and antibiofilm properties and may contribute to the anti-infectious traditional uses of L. capitata, meriting further clinical studies and serving as a reliable quality control biomarker for the plant.

Identification of aurones and chalcones as the main contributors to xanthine oxidase inhibitory activity of snow chrysanthemum

Snow chrysanthemum, the capitulum of Coreopsis tinctoria Nutt., was found to possess inhibitory activity on xanthine oxidase (XO), one of the key enzymes in the pathogenesis of gout. Assisted by bioactivity-oriented isolation, a total of 16 compounds containing a new compound were obtained from the active fractions of snow chrysanthemum extract, including two aurones (1, 2), four chalcones (3–6), a flavone (7), four flavonols (8-11), a flavanonol (12), three phenylpropanoids (13–15), and a new polyacetylene glycoside (16). All the isolated compounds were assayed for their inhibitory activity on XO, among which eight polyphenols (1–8) exhibited potent or moderate inhibitory activities with IC50 values from 0.65 to 29.11 μM. The structure-activity relationship was interpreted for polyphenols (1-12). Besides, the inhibition properties of compounds 1–4 against XO were comprehensively investigated through enzyme kinetics, fluorescence quenching, and docking simulation. Maritimetin (1) and sulfurein (2) reversibly inhibited XO by mixed type mechanism. Okanin-4′-O-(6″-acetyl)-β-d-glucopyranoside (3) and coreopsin (4) competitively inhibited XO in reversible and irreversible manners, respectively. In addition, fluorescence quenching studies suggested that all four compounds interacted with XO through a static quenching mechanism. Molecular docking inferred that hydrogen bonds and hydrophobic interaction played key roles in the binding process. This study revealed the XO-inhibitory activity of snow chrysanthemum and the contribution of containing aurones and chalcones to XO inhibition, making it a potential functional food ingredient for management of hyperuricemia.

Phytochemical and chemotaxonomic study on Atractylodes lancea

Based on previous studies on Atractylodes lancea (Thunb.) DC., this paper focuses on the chemical composition of fresh rhizome of Atractylodes lancea. And fifteen compounds were isolated, including six guaiane-type sesquiterpenoids (1–5), one eudesmane-type sesquiterpenoid (6), one monoterpene glycoside (7), one polyacetylene glycoside (8), one phenylpropanoid glycoside (9), two nucleosides (10–11), one alkaloid (12), one amino acid (13), one purine (14) and one fatty acid (15). The structures of the isolated compounds (1–15) were elucidated by 1H and 13C NMR spectroscopic analyses and comparisons with previously reported data. Compounds 7 and 12 were isolated from the Compositae family for the first time. Compound 11 was isolated from genus Atractylodes for the first time. Compound 14 was isolated from this plant for the first time. Furthermore, the chemotaxonomic significance of these isolates was discussed.

In Vitro and In Silico Investigation of Polyacetylenes from Launaea capitata (Spreng.) Dandy as Potential COX-2, 5-LOX, and BchE Inhibitors.

Diverse secondary metabolites are biosynthesized by plants via various enzymatic cascades. These have the capacity to interact with various human receptors, particularly enzymes implicated in the etiology of several diseases. The n-hexane fraction of the whole plant extract of the wild edible plant, Launaea capitata (Spreng.) Dandy was purified by column chromatography. Five polyacetylene derivatives were identified, including (3S,8E)-deca-8-en-4,6-diyne-1,3-diol (1A), (3S)-deca-4,6,8-triyne-1,3-diol (1B), (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (2), bidensyneoside (3), and (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1-ol-3-O-β-D-glucopyranoside (4). These compounds were investigated for their in vitro inhibitory activity against enzymes involved in neuroinflammatory disorders, including cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and butyrylcholinesterase (BchE) enzymes. All isolates recorded weak-moderate activities against COX-2. However, the polyacetylene glycoside (4) showed dual inhibition against BchE (IC50 14.77 ± 1.55 μM) and 5-LOX (IC50 34.59 ± 4.26 μM). Molecular docking experiments were conducted to explain these results, which showed that compound 4 exhibited greater binding affinity to 5-LOX (-8.132 kcal/mol) compared to the cocrystallized ligand (-6.218 kcal/mol). Similarly, 4 showed a good binding affinity to BchE (-7.305 kcal/mol), which was comparable to the cocrystallized ligand (-8.049 kcal/mol). Simultaneous docking was used to study the combinatorial affinity of the unresolved mixture 1A/1B to the active sites of the tested enzymes. Generally, the individual molecules showed lower docking scores against all the investigated targets compared to their combination, which was consistent with the in vitro results. This study demonstrated that the presence of a sugar moiety (in 3 and 4) resulted in dual inhibition of 5-LOX and BchE enzymes compared to their free polyacetylenes analogs. Thus, polyacetylene glycosides could be suggested as potential leads for developing new inhibitors against the enzymes involved in neuroinflammation.

Polyacetylene Glycosides: Isolation, Biological Activities and Synthesis.

Polyacetylene glycosides (PAGs) constitute a relatively small class of secondary metabolites characterized by the presence of a sugar unit anomerically connected to a polyacetylene. These compounds are found in fungi, seaweed, and more often in plants. PAGs exhibit a wide range of biological and pharmacological activities and, as a result, the literature of these compounds has grown exponentially in recent years.

Anti-Adipogenic Polyacetylene Glycosides from the Florets of Safflower (Carthamus tinctorius).

Safflower (Carthamus tinctorius) is an annual herb belonging to the Compositae family; it has a history of use as a food colorant, dye, and medicine in oriental countries. LC-MS-UV-based chemical analysis of extract of the florets of C. tinctorius led to the isolation of two new C10-polyacetylene glycosides, (8Z)-decaene-4,6-diyne-1,10-diol-1-O-β-d-glucopyranoside (1) and (8S)-deca-4,6-diyne-1,8-diol-1-O-β-d-glucopyranoside (2), together with five known analogs (3–7). The structures of the new compounds were determined by using 1D and 2D NMR spectroscopic data and HR-MS data, as well as chemical transformations. Of compounds 1–7, compounds 2, 3, and 4 inhibited the adipogenesis of 3T3-L1 preadipocytes, whereas compounds 1 and 6 promoted adipogenesis. Compounds 2, 3, and 4 also prevented lipid accumulation through the suppression of the expression of lipogenic genes and the increase of the expression of lipolytic genes. Moreover, compounds 3 and 4 activated AMPK, which is known to facilitate lipid metabolism. Our findings provide a mechanistic rationale for the use of safflower-derived polyacetylene glycosides as potential therapeutic agents against obesity.

Constituents of Coreopsis lanceolata Flower and Their Dipeptidyl Peptidase IV Inhibitory Effects.

A new polyacetylene glycoside, (5R)-6E-tetradecene-8,10,12-triyne-1-ol-5-O-β-glucoside (1), was isolated from the flower of Coreopsis lanceolata (Compositae), together with two known compounds, bidenoside C (10) and (3S,4S)-5E-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-glucopyranoside (11), which were found in Coreopsis species for the first time. The other known compounds, lanceoletin (2), 3,2′-dihydroxy-4-3′-dimethoxychalcone-4′-glucoside (3), 4-methoxylanceoletin (4), lanceolin (5), leptosidin (6), (2R)-8-methoxybutin (7), luteolin (8) and quercetin (9), were isolated in this study and reported previously from this plant. The structure of 1 was elucidated by analyzing one-dimensional and two-dimensional nuclear magnetic resonance and high resolution-electrospray ionization-mass spectrometry data. All compounds were tested for their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and compounds 2-4, 6 and 7 inhibited DPP-IV activity in a concentration-dependent manner, with IC50 values from 9.6 to 64.9 μM. These results suggest that C. lanceolata flower and its active constituents show potential as therapeutic agents for diseases associated with type 2 diabetes mellitus.

Kamiohnoyneosides A and B, two new polyacetylene glycosides from flowers of edible Chrysanthemum "Kamiohno".

Two new polyacetylene glycosides, kamiohnoyneosides A and B, were isolated from the flowers of edible Chrysanthemum "Kamiohno", along with a known polyacetylene glycoside and two known monoterpene glycosides. The structures of new compounds were elucidated on the basis of spectroscopic data. Kamiohnoyneoside A and three known compounds moderately inhibited formation of Nε-(carboxymethyl)lysine, one of the representative advancedglycation endproducts.

Three new polyacetylene glycosides (PAGs) from the aerial part of Launaea capitata (Asteraceae) with anti-biofilm activity against Staphylococcus aureus

Four polyacetylenic glycosides, three of which are new, together with two known flavonoids were isolated from the methanol extract of the aerial parts of Launaea capitate, designated bidensyneoside A1 (1), 6´–O-acetyl-bidensyneoside A1 (2), bidensyneoside E (3), bidensyneoside F (4), luteolin (5) and luteolin-7-glucoside (6) also known as cynaroside. Their structures were elucidated by comprehensive analysis of 1D, 2D-NMR and HR-MS data. The absolute configuration of the bidensyneosides was determined by Mosher ester analysis and the optical rotation values. The isolated compounds were tested against biofilm formation of Staphylococcus aureus as well as against several pathogens including Gram-positive bacteria, Gram-negative bacteria, fungi and yeasts. Furthermore, they were tested for their cytotoxicity against two cancer cell lines L929 and KB-3-1. Compound 4 showed moderate inhibition of S. aureus biofilm formation with 30% and 25% at 256 and 128 μg/mL, respectively, while compounds 1 and 5 showed weak inhibition with 20% at 256 μg/mL. Compound 5 showed moderate cytotoxicity against both cell lines L929 and KB-3-1, with IC50 values of 18 μg/mL.

Cytotoxic Secondary Metabolites from the Endolichenic Fungus Hypoxylon fuscum.

As part of our search for new cytotoxic and antimicrobial natural products from endolichenic fungi, 19 compounds including 1 new 10-member lactone (2: ), 1 new polyacetylene glycoside (3: ), 1 new brasilane-type sesquiterpenoid glycoside (4: ), and 2 isobenzofuran-1(3H)-one derivatives (5: and 6: ) were isolated from the solid culture of the endolichenic fungus Hypoxylon fuscum. Their structures were unambiguously elucidated by NMR spectroscopic data, MS, ECD (electronic circular dichroism) calculation, and chemical methods. The cytotoxic effects on K562, SW480, and HEPG2 cell lines and the antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans were assessed. Compounds 1, 2: , and 5: exhibited moderate cytotoxicity against K562, SW480, and HEPG2 cell lines while compounds 1, 9: , and 11: displayed weak antibacterial activity against S.aureus.

Three New Polyacetylene Glycosides from the Roots of Heracleum dissectum and Their Triglyceride Accumulating Activities in 3T3-L1 Cells.

Continually phytochemical study of the roots of Heracleum dissectum had led to the isolation of three previously undescribed polyacetylene glycosides (1-3), together with seven known compounds, including one polyacetylene (8) and six coumarins (4-7 and 9-10) using diverse chromatographic methods. The structures of these three new compounds were characterized and identified as deca-4,6-diyn-1-yl β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (1), (8Z)-dec-8-ene-4,6-diyn-1-yl β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (2), and (8E)-dec-8-ene-4,6-diyn-1-yl β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (3) based on their physicochemical properties and extensive analyses of various spectroscopic data. Their triglycerides accumulating activities were assayed and the results showed that the three new polyacetylene glycosides (1-3) exhibited triglyceride accumulating activities in 3T3-L1 adipocytes.

New polyacetylenes glycoside from Eclipta prostrate with DGAT inhibitory activity

One new polyacetylene glycoside eprostrata Ⅰ (1), together with seven known compounds (2–8), were isolated from Eclipta prostrata. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated inhibitory activity on DGAT in an in vitro assay. Compounds 1–8 were found to exhibit inhibitory activity of DGAT1 with IC50 values ranging from 74.4 ± 1.3 to 101.1 ± 1.1 μM.

Polyacetylene glycoside attenuates ischemic kidney injury by co-inhibiting inflammation, mitochondria dysfunction and lipotoxicity

AimsIschemic acute kidney injury (AKI) is a serious clinical problem and no efficient therapeutics is available in clinic now. Natural polyacetylene glycosides (PGAs) had shown antioxidant and anti-inflammatory properties, but their effects on kidney injury have not been evaluated. This study aimed to investigate the protective effect of PGA on ischemic kidney injury in renal tubular epithelial cells (TECs) and mice. Main methodsHypoxic HK-2 cells and renal ischemia/reperfusion injury (IRI) mice were treated with PGA from Coreopsis tinctoria, and the cell viability, renal function, apoptosis, inflammation, mitochondrial injury, lipids metabolism were analyzed. Key findingsIn vitro results showed that PGA improved cell viability and reduced oxidative stress, pro-apoptotic/pro-inflammatory factors expression and NFκB activation in TECs under hypoxia/reperfusion (H/R). Moreover, PGA reduced mitochondria oxidative stress and improved ATP production, ΔΨm and mitochondria biogenesis, and inhibited lipids uptake, biosynthesis and accumulation in hypoxic TECs. In vivo, PGA significantly attenuated kidney injury and reduced blood urea nitrogen (BUN), serum creatinine (CREA) and urinary albumin (Alb), and increased creatinine clearance (CC) in IRI mice. PGA also decreased cell apoptosis, mitochondria oxidative stress, inflammatory response and lipid droplets accumulation, and promoted ATP generation in kidney of IRI mice. SignificanceOur results proved that PGA ameliorated ischemic kidney injury via synergic anti-inflammation, mitochondria protection and anti-lipotoxicity actions, and it might be a promising multi-target therapy for ischemic AKI.

Two new thiophene polyacetylene glycosides from Atractylodes lancea

Phytochemical investigation on the rhizomes of Atractylodes lancea led to the isolation of two new thiophene polyacetylene glycosides (1 and 2) and six known compounds (3-8). Their structures were elucidated based on the extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of new compounds were established by calculated and experimental circular dichroism. All the compounds were assessed on the lipopolysaccharide-induced NO production in BV2 cells and compounds 3, 7, and 8 showed moderate inhibitory activities.

Direct Assignment of the Threo and Erythro Configurations in Polyacetylene Glycosides by 1H NMR Spectroscopy.

An approach for discriminating the threo and erythro configurations of polyacetylene glycosides by 1H NMR spectroscopy was developed. Using acetic acid-d4/D2O as the solvent, a relatively larger 3JHH value (7.0 Hz) for the acyclic vicinal diol group was unambiguously assigned to the threo configuration, whereas the smaller value (3.5 Hz) was assigned to the erythro configuration. This convenient method requires no hydrolysis or derivatization and is suitable for micromolar concentrations of polyacetylene glycosides. The underlying mechanism is discussed via visualized conformations.

Isolation, characterization and antimicrobial activities of polyacetylene glycosides from Coreopsis tinctoria Nutt.

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.

Four new C10-polyacetylene glycosides from the rhizomes of Atractylodes lancea

An ongoing phytochemical investigation of the rhizomes of Atractylodes lancea resulted in the isolation of four new C10-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.

Two new polyacetylene glycosides from the roots of Codonopsis tangshen Oliv.

Two new polyacetylene glycosides, tangshenyne A (1) and tangshenyne B (2), along with six known polyacetylenes were isolated from an 85% MeOH extract of the roots of Codonopsis tangshen Oliv. The chemical structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including UV, IR, 1D and 2D NMR (1H–1H COSY, HSQC and HMBC) and HR-ESI-MS.