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Enantiomer-specific identification of chiral molecules in natural extracts is a challenging task, as many routine analytical techniques fail to provide selectivity in multicomponent mixtures. Here we describe an alternative approach, based on the combination of ion mobility-mass spectrometry (IM-MS) and quantum chemistry (QM), for the direct enantiomers differentiation in crude essential oils. The identification of α-bisabolol enantiomers contained in the raw essential oil (EO) from the Corsican Xanthium italicum fruits is reported as a proof-of-concept. Accordingly, IM-MS experiments performed in Ag + -doped methanol revealed the presence of both (+)- and (-)-α-bisabolol in the EO, while molecular simulations provided the structures of the two α-bisabolol enantiomer silver(I) adducts.

The development of bacterial antibiotic resistance poses a danger to healthcare systems worldwide. To reduce the spread of disease, researchers are looking for novel measures to control bacterial infections to reduce the spread of disease. The antibacterial properties of Xanthium strumarium methanolic and ethanolic extracts were evaluated against Enterobacter cloacae and E. hormaeche isolated from some invertebrates (Porcellio laevis, Armadillidium sp. (isopods), and Archispirostreptus syriacus). All Enterobacter strains tested positive for the presence of the virulence genes csgA, csgD, AcrAB, fimH, and Hsp60. Extracts of X. strumarium had significant anti-biofilm activity against E. cloacae and E. hormaechei. The disruption of established biofilm growth by the plant samples proved to be effective against E. cloacae and E. hormaechei. Both E. cloacae and E. hormaechei showed inhibition of biofilm formation and promotion of biofilm eradication in response to X. strumarium extract. Phenolic compounds such as ferulic acid, chlorogenic acid, and trans-cinnamic acid, and flavonoids such as kaempferol were the most abundant components in the extract and might play crucial roles in the extract's antibacterial and antibiofilm action. Results suggest that ethanolic leaf extracts from X. strumarium show potential as a novel approach to prevent infections caused by E. cloacae and E. hormaechei.

Two protoberberine alkaloids with a unique C 28 skeleton, named xanthiumines A (1) and B (2), respectively, were isolated from the fruits of Xanthium sibiricum Patr. Their structures including absolute configurations were unequivocally established by the comprehensive NMR and MS spectroscopic data analysis together with gauge-independent atomic orbital (GIAO) NMR calculations, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are the first examples of natural protoberberine alkaloid with a phenolic acid group at C-13a. Their plausible biosynthetic pathway was proposed on the basis of the coexisting alkaloid monomer as the precursor. Furthermore, the effects and related molecular mechanism of compound 1 on hepatic lipid accumulation were also investigated in oleic acid (OA)-treated HepG2 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 © 2024. Published by Elsevier Inc.)

One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3-12), two eudesmene sesquiterpene derivatives (13-14), one phenylpropionic acid derivative (15), together with eleven known compounds (16-26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4-5, 18-21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4-5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources., 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.)

Introduction: Cancer is one of the leading causes of death worldwide, accounting for nearly one in six deaths in 2020. As a folk medicine, Xanthium sibiricum Herba (XSH) has been used many times in clinical practice for the treatment of various diseases. With the increasing number of cancer patients, there is a clinical need to find effective anti-cancer drugs., Aim: This study aims to explores the bioactivity and the anti-cancer mechanism of XSH., Methods: In this study, bioinformatics, network pharmacology, molecular docking, molecular dynamics simulation techniques, and apoptosis assay were used to explore the bioactivity and the anti- cancer mechanism of XSH., Results: Finally, seven active ingredients in XSH after the screening were obtained, the two most active compounds were β-sitosterol and aloe-emodin, and good anti-cancer activity of XSH was predicted., Discussion: Four core targets were obtained from the PPI network map, namely Caspase-3 (CASP3), Transcription factor AP-1 (JUN), Myc proto-oncogene protein (MYC), and cellular tumor antigen p53 (TP53). GO and KEGG analyses showed that the mechanism of XSH anti-cancer is mainly related to the apoptosis process, and the main signaling pathways are enriched in the p53 signaling pathway, Apoptosis, and MAPK signaling. The molecular docking and molecular dynamics simulation results showed that CASP3, JUN, MYC, and TP53 had a high affinity with β- sitosterol and aloe-emodin. Bioinformatics analyses demonstrated the importance of core targets. Apoptosis assay showed that XSH could significantly promote the apoptosis of cancer cells, and inhibit their proliferation and migration, especially colon cancer cells., Conclusion: This study uncovered the main active components, bioactivities, and potential targets of XSH, and further revealed the multi-component, multi-target, and multi-pathway mechanism of XSH for cancer treatment and promoting apoptosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As part of our ongoing efforts to discover novel agricultural fungicidal candidates from natural sesquiterpene lactones, in the present work, sixty-three xanthatin-based derivatives containing a arylpyrazole, arylimine, thio-acylamino, oxime, oxime ether, or oxime ester moiety were synthesized. Their structures were well characterized by 1 H and 13 C nuclear magnetic resonance and high-resolution mass spectrometry, while the absolute configurations of compounds 5' and 6a were further determined by single-crystal X-ray diffraction. Meanwhile, the antifungal activities of the prepared compounds against several phytopathogenic fungi were investigated using the spore germination method and the mycelium growth rate method in vitro . The bioassay results illustrated that compounds 5 , 5' , and 15 exhibited excellent inhibitory activity against the tested fungal spores and displayed remarkable inhibitory effects on fungal mycelia. Compounds 5 and 5' exhibited more potent inhibitory activity (IC 50 = 1.1 and 24.8 μg/mL, respectively) against the spore of Botrytis cinerea than their precursor xanthatin (IC 50 = 37.6 μg/mL), wherein the antifungal activity of compound 5 was 34-fold higher than that of xanthatin and 71-fold higher than that of the positive control, difenoconazole (IC 50 = 78.5 μg/mL). Notably, compound 6'a also demonstrated broad-spectrum inhibitory activity against the four tested fungal spores. Meanwhile, compounds 2 , 5 , 8 , and 15 showed prominent inhibitory activity against the mycelia of Cytospora mandshurica with the EC 50 values of 2.3, 11.7, 11.1, and 3.0 μg/mL, respectively, whereas the EC 50 value of xanthatin was 14.8 μg/mL. Additionally, compounds 5' and 15 exhibited good in vivo therapeutic and protective effects against B. cinerea with values of 55.4 and 62.8%, respectively. The preliminary structure-activity relationship analysis revealed that the introduction of oxime, oxime ether, or oxime ester structural fragment at the C-4 position of xanthatin or the introduction of a chlorine atom at the C-3 position of xanthatin might be significantly beneficial to antifungal activity. In conclusion, the comprehensive investigation indicated that partial xanthatin-based derivatives from this study could be considered for further exploration as potential lead structures toward developing novel fungicidal candidates for crop protection.

The traditional Chinese medicine Xanthium sibiricum Patrin ex Widder is used to treat wind-cold headache, nasal congestion, nasal discharge, allergic rhinitis, sinusitis, urticaria, and arthritis. Our previous studies found that sesquiterpene lactones, the main bioactive constituents of X. sibiricum, relieved airway inflammation in an asthma mouse model. To obtain active sesquiterpenes, five undescribed ones, including a pair of eremophilanes and three xanthanolides, together with eight known xanthanolides were isolated from X. sibiricum. Their structures were identified by IR, UV, HR-ESI-MS and NMR spectroscopic data, and their absolute configurations were determined by X-ray crystallographic diffraction analysis and the comparison between their experimental and calculated electronic circular dichroism. All isolated compounds were evaluated for their inhibitory effects on nitric oxide production, and Tnf-α, Il-1β, and Il-6 mRNA expression induced by lipopolysaccharide in the macrophage cell line RAW264.7. Further investigation showed that xanthsibiriolide and 11β-hydroxyl-13-chloro-8-epi-xanthatin exerted their anti-inflammatory effects by inhibiting the PI3K/AKT/mTOR signaling pathway. Analysis of the structure-activity relationships indicated that the α,β-unsaturated lactone ring and the 1,5-epoxide group might be the bioactive groups of xanthanolides, and these results provide a basis for further exploration of sesquiterpene-type lead compounds with anti-inflammatory activity., 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 © 2023 Elsevier Ltd. All rights reserved.)

Xanthanolides were particularly characteristic of the genus Xanthium , which exhibited broad biological effects and have drawn much attention in pharmacological application. The review surveyed the structures and bioactivities of the xanthanolides in the genus Xanthium , and summarized the synthesis tactics of xanthanolides. The results indicated that over 30 naturally occurring xanthanolides have been isolated from the genus Xanthium in monomeric, dimeric and trimeric forms. The bioassay-guided fractionation studies suggested that the effective fractions on antitumor activities were mostly from weak polar solvents, and xanthatin ( 1 ) was the most effective and well-studied xanthanolide. The varieties of structures and structure-activity relationships of the xanthanolides had provided the promising skeleton for the further study. The review aimed at providing guidance for the efficient preparation and the potential prospects of the xanthanolides in the medicinal industry.

Ziniolide, xantholide B (11α-dihydroziniolide), and 11β-dihydroziniolide, three sesquiterpene lactones with 12,8-guaianolide skeletons, were identified as volatile metabolites from the roots of Xanthium spinosum L., an invasive plant harvested in Corsica. Essential oil, as well as hydrosol and hexane extracts, showed the presence of guaianolide analogues. The study highlights an analytical strategy involving column chromatography, GC-FID, GC-MS, NMR (1D and 2D), and the hemi-synthesis approach, to identify compounds with incomplete or even missing spectral data from the literature. Among them, we reported the 1 H- and 13 C-NMR data of 11β-dihydroziniolide, which was observed as a natural product for the first time. As secondary metabolites were frequently involved in the dynamic of the dispersion of weed species, the allelopathic effects of X. spinosum root's volatile metabolites were assessed on seed germination and seedling growth (leek and radish). Essential oil, as well as hydrosol- and microwave-assisted extracts inhibited germination and seedling growth; root metabolite phytotoxicity was demonstrated. Nevertheless, the phytotoxicity of root metabolites was demonstrated with a more marked selectivity to the benefit of the monocotyledonous species compared to the dicotyledonous species. Ziniolide derivatives seem to be strongly involved in allelopathic interactions and could be the key to understanding the invasive mechanisms of weed.

Four new germacrane-type sesquiterpenoids ( 1 - 4 ) and two new guaiane-type sesquiterpenoids ( 5 - 6 ) were isolated from the fruits of Xanthium italicum Moretti. The structures of the new compounds were elucidated on the basis of spectroscopic analysis and X-ray diffraction experiment. Compounds 1 , 2 and 6 showed the anti-inflammatory effects against the activation of NF-κB induced by lipopolysaccharide (LPS) with IC 50 values of 20.12, 22.89 and 68.66 µM, respectively.

In this study, the therapeutic effects of puerarin on Xanthium strumarium toxicity, which can develop in many species and does not have a specific antidote, were investigated. A single dose of 100 g/kg X. strumarium seeds was administered by gavage to female Sprague-Dawley rats, 6 h following which 200 mg/kg puerarin was administered by the same route, with puerarin administration being repeated daily at the same time. After completing the application, the blood, liver and kidney tissues of the rats were examined. Further, the biochemical parameters, glucose, MDA, GSH, SOD, mitochondrial Ca 2+ and mitochondrial permeability transition pore (mPTP) opening levels, apoptotic factors (TUNEL, Bax and Bcl-2), ATP synthase and histopathological changes of the experimental rats were examined. The results revealed that while the administration of X. strumarium resulted in increased blood AST, ALT, ALP, LDH, CK, BUN and creatinine levels, it decreased glucose levels. In addition, it increased the MDA levels in the tissues and significantly increased the oxidative stress levels by decreasing the GSH levels and SOD activity. X. strumarium caused an increase in the mitochondrial Ca 2+ and mPTP opening levels. Moreover, it increased the immunohistochemically determined ATP synthase expression and histopathologically identified necrotic liver cell death rates. Owing to its antioxidant properties and inhibitory effects on mPTP opening, puerarin administered for therapeutic purposes decreased the oxidative damage caused by X. strumarium toxicity, blood biochemical parameter levels, mitochondrial Ca 2+ levels, mPTP opening, ATP synthase expression and the percentage of necrotic cells. Hence, the reduction in the liver and kidney damage in X. strumarium toxicity by puerarin indicates its potential use as an antidote for X. strumarium poisoning., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A pair of new lignans [(+)- 1 and (-)- 1 ] and three new compounds ( 2-4 ), together with a known compound 5 , were isolated from the fruits of Xanthium italicum Moretti. The structures of these compounds were determined on the basis of spectroscopic analysis, particularly HR-ESI-MS and 1 D and 2 D NMR. Compounds 2 and 3 showed antinociceptive effects in an acetic acid-induced writhing test in mice with the writhe inhibition rates of 80.50% and 67.89% at the dose of 20 mg/kg, respectively.

The chemical investigation of the fruits of Xanthium strumarium (Asteraceae) led to the isolation of two new ent -kauranoid glucosides named 2- O -(6- O -isocaleryl- β -D-glucopyranosyl) atractyligenin ( 1 ) and 2- O -(2- O -isovaleryl- β -D-glucopyranosyl) atractyligenin ( 2 ), together with one known compound. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction and electronic circular dichroism data. All compounds and their aglycone were evaluated for their anti-proliferative activities in vitro against three human cancer cell lines.

Eight pentacyclic triterpenoids including two new ones (1, 2) were isolated from the fruits of Xanthium strumarium. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated for in vitro cytotoxic activity on HepG2, A549, HCT116 and SW480 cancer cells. Among them, the new compound 2 was found to exhibit significant cytotoxic activity on A549, HCT116 and SW480 cancer cells with IC 50 values of 9.68, 4.27 and 7.58 μM, respectively. Further, 2 was selected for cell cycle analysis and results revealed that 2 could cause HCT116 cell cycle arrest in G1 phase. In addition, Annexin V-FITC/PI staining assay showed that 2 could induce the death of HCT116 cells., (© 2021. The Japanese Society of Pharmacognosy.)

In the present study isoxanthanol was investigated for treatment of monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in vivo. The study demonstrated that isoxanthanol inhibited excessive release of interleukin-6, NO and PGE2 in RAW264.7 cells treated with LPS in dose dependent manner. The effects of isoxanthanol were examined in a rat model of osteoarthritis (OA) and observed to amelio-rate inflammatory damage and protect against OA. Moreover, in vivo data also confirmed inhibition of interleukin-6, NO and PGE2 levels in LPS-induced OA-rats. Deterioration of knee subchondral bone in LPS-induced OA-rats was also prevented effectively by isoxanthanol-treatment. Therefore, isoxanthanol prevents subchondral bone deterioration in OA rats via targeting inflammatory processes.

Two new flavonoid glycosides named 6-hydroxy-3-methoxy-apigenin 7- O - α -ʟ-rhamnopyranoside ( 1 ) and 3-hydroxyl-apigenin 8-C- β -ᴅ-xylopyranoside ( 2 ), along with five known compounds ( 3-7 ), were isolated from Xanthium strumarium . Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All compounds were evaluated for in vitro inhibitory activity against PTP1B. Among them, compounds 1 and 5 showed significant inhibitory activity on PTP1B with IC 50 values of 11.3 ± 1.7 and 8.9 ± 0.7 μM, respectively.

Structural optimization using plant secondary metabolites as templates is one of the important approach to discover pesticide molecules with novel skeletons. Xanthatin, a natural sesquiterpene lactone isolated from the Xanthium plants (Family: Compositae), exhibits important biological properties. In this work, a series of Michael-type amino derivatives were prepared from xanthatin and their structures were characterized by 1 H NMR, 13 C NMR and HR-MS, and their antifungal activities against several phytopathogenic fungi were evaluated according to the spore germination method and mycelium growth rate method in vitro. The results illustrated that compounds 2g (IC 50  = 78.91 µg/mL) and 2o (IC 50  = 64.51 µg/mL) exhibited more promising inhibition activity against spores of F. solani than precursor xanthatin, compounds 2g, 2l, and 2r exhibited remarkable antifungal effect on C. mandshurica with the average inhibition rates (AIRs) >90%, whereas the AIR of xanthatin was only 59.34%. Meanwhile, the preliminary structure-activity relationships suggested that the amino containing 2-methoxyethyl or 4-chlorophenylmethyl group appended in the C-13 position of xanthatin could yield potential compounds against fungal spores, and the exocyclic double bond of xanthatin is essential to maintain its mycelial growth inhibitory activity. Therefore, the aforementioned findings indicate that partial xanthatin amino-derivatives could be considered for further exploration as the potential lead structures toward development of the new environmentally friendly fungicidal candidates for sustainable crop protection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Inspired by the allelopathetic effects of Xanthium orientale subsp . italicum (Moretti) Greuter , bioassay-guided isolation was employed to identify its antitumor constituents and clarify the chemical basis of its multitarget activity. Among four fractions of X.orientale extraction, TCM-fr and PE-fr were discovered to exhibit significant cytotoxicity aganist HepG two and A549 cells, which were further isolated by chromatographic methods to yield 16 compounds, including six active ones: xanthatin ( 1 ), xanthinosin ( 2 ), lupeol ( 6 ), oleanolic acid ( 9 ), betulinic acid ( 10 ) and emodin ( 12 ) with IC 50 of 10 ∼ 120μM. The systematically study of antitumor constituents has firstly provided a chemical basis for the multitarget and synergistic anticancer activity of the genus Xanthium . The method presented could be utilized to guide the exploitation and promising utilization of X. orientale on cancer therapy.

The present study investigated integrated effects of two allelopathic plant water extracts (WE) ( Ambrosia artemisiifolia [AMBEL] and Xanthium strumarium [XANST]) and a herbicide (mesotrione) on morphological (height and fresh weight of plants) and physiological (pigments content) parameters of Abutilon theophrasti and Chenopodium album . Also, the study aimed to identify the main components of AMBEL and XANST WE and to evaluate their potential allelopathic effects. Of the 18 investigated compounds, 13 were detected in both tested WE, and p -coumaric acid was the leading component in AMBEL, while quinic acid was the predominant component of XANST. The WE of both weed species and their mixtures with the herbicide exhibited more powerful allelopathic effects on fresh weight and content of pigments than on the height of A. theophrasti and C. album . The results showed that all measured parameters of both weeds were inhibited in treatments with mesotrione and its mix with AMBEL and XANST WE. The data revealed a highly significant difference in effects ( P  < 0.05) between control weeds and those treated with AMBEL WE and mesotrione, where the inhibition of fresh weight was over 90%, while the inhibition of pigments content exceeded 80%, and plant height was inhibited by over 70%.

Xanthatin is a natural plant bicyclic sesquiterpene lactone extracted from Xanthium plants (Asteraceae). In the present study, we demonstrated for the first time that Xanthatin inhibited cell proliferation and mediated G 2 /M phase arrest in human colon cancer cells. Xanthatin also activated caspase and mediated apoptosis in these cells. Concomitantly, Xanthatin triggered cell autophagic response. We found down-regulation of X-linked inhibitor of apoptosis protein (XIAP) contribute to the induction of apoptosis and autophagy. Moreover, reactive oxygen species (ROS) production was triggered upon exposure to Xanthatin in colon cancer cells. ROS inhibitor N-acetylcysteine (NAC) significantly reversed Xanthatin-mediated XIAP down-regulation, G 2 /M phase arrest, apoptosis and autophagosome accumulation. In summary, our findings demonstrated that Xanthatin caused G 2 /M phase arrest and mediated apoptosis and autophagy through ROS/XIAP in human colon cancer cells. We provided molecular bases for developing Xanthatin as a promising antitumor candidate for colon cancer therapy. AbbreviationsROSreactive oxygen speciesDMSOdimethyl sulfoxide5-FU5-Fluorouracil3-MA3-MethyladenineDCFH-DA2'7'-dichlorfluorescein-diacetateNACN-acetylcysteineXIAPX-linked inhibitor of apoptosis protein.

Ethnopharmacological Relevance: Ethnobotanical surveys revealed that Xanthiumorientale subsp. italicum (Moretti) Greuter has been used against central nervous system disorders in Turkish folk medicine. The aim of the present study is to verify the folkloric assertion on this plant. The compounds responsible for the activity were investigated using bioassay-guided fractionation procedures., Materials and Methods: The antidepressant activity of the aqueous, n-hexane, ethyl acetate (EtOAc), methanol (MeOH) extracts; fractions and isolated compounds from active MeOH extract were evaluated by using the in vitro MAO inhibition assay and three different in vivo models namely forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. The results were compared with control and reference groups, and active compounds of the plant have been determined. Through the bioassay-guided fractionation procedures, two compounds were isolated from the active fraction and their structures were elucidated by spectroscopic methods., Results: The MeOH extract of the plant was found to possess antidepressant-like activity. This extract was then subjected to chromatographic techniques. Isolated sesquiterpene lactones were elucidated as xanthatin (1) and xanthinosin (2), which were responsible for the antidepressant-like activity., Conclusions: This study discovered the antidepressant potential of X. orientale subsp. italicum. Using bioassay-guided fractionation and isolation techniques, xanthatin (1) and xanthinosin (2) were determined as the main active components of the leaves., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Xanthatin, a natural sesquiterpene lactone, occurs as one of the major constituents of Xanthium plants (Compositae) and exhibits many important biological properties. To discover natural products-based pesticides, forty-nine Michael-type thiol/amino adducts of xanthatin were synthesized and characterized, while their pesticidal activities were investigated. Among them, compounds 2c, 2h, 2i, and 2t exhibited more potent antifungal activity against Botrytis cinerea (IC 50  = 0.96, 0.38, 6.33, and 7.21 µg/mL, respectively) than xanthatin and the two commercial fungicides. Compounds 2t and 2u displayed broad-spectrum and excellent antifungal effects against all tested phytopathogenic fungi, while their IC 50 values ranged from 7.21 to 75.88 µg/mL. Compounds 2a, 2f, 2l, 2m, 2v, 7c, 7e, 7h, 7i, and 7j showed moderate larvicidal activity against Plutella xylostella Linnaeus. Furthermore, compounds 2b, 7g, and 7h demonstrated significant ovicidal activity against P. xylostella with the LC 50 values of 14.04, 10.00, and 11.95 mg/L, respectively. These findings suggest that thiol/amino appended in the C-13 position of xanthatin may improve antifungal and ovicidal activities for the derivatives. It was also noticed that the exocyclic double bond of xanthatin is crucial for its larvicidal activity. This work also provides some important hints for further design, synthesis, and structural modification of the xanthanolides sesquiterpene lactones toward development of the new environmentally friendly pesticides for sustainable agricultural production., 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 Inc. All rights reserved.)

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 μM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg -1 ·d -1 , ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

Xanthii Fructus is extensively used as an herbal medicine. Ingestion of this herb is associated with severe hepatotoxicity and nephrotoxicity. Atractyloside and carboxyatractyloside are two dominative toxic constituents in Xanthii Fructus. However, their pharmacokinetic study is lacking. In this study, a novel high-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously quantify the rat plasma concentrations of atractyloside and carboxyatractyloside. After protein precipitation, the analytes were chromatographic separated on a ZORBAX Eclipse Plus column (2.1 × 150 mm id, 5 µm) under gradient elute. In the negative electrospray ionization mode, the transitions at m/z 725.3→645.4 for atractyloside, m/z 769.3→689.4 for carboxyatractyloside, and m/z 479.2→121.1 for paeoniflorin (the internal standard) were acquired by multiple reaction monitoring. This analytical method showed good linearity over 1-500 ng/mL for atractyloside and 2-500 ng/mL for carboxyatractyloside with acceptable precision and accuracy. No matrix effect, instability and carryover occurred in the analysis procedure. The extraction recoveries were greater than 85.0%. This method was applied to a preliminary pharmacokinetic study by orally administering Xanthii Fructus extract (9 g/kg) to rats, which was useful to evaluate the role of these two compounds in Xanthii Fructus-induced toxicity., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two new monoterpene glucosides: xanmonoter A (1) and xanmonoter B ( 2 ) were isolated from Xanthium strumarium . Their structures were elucidated on the basis of 1D and 2D NMR, MS and CD analysis. Compounds 1 and 2 were tested for their anti-inflammatory activity with IC 50 values of 17.4, 22.1 μM, respectively.

Xanthii Fructus (XF) is known as a medicinal plant. It has been used as a traditional medicine because of its high biological efficacy. However, there have been few comprehensive studies on the specific chemical composition of the plant and consequently, the information is lacking for the mechanism of the natural product metabolites in humans. In this study, an efficient analytical method to characterize and discriminate two species of Xanthii Fructus ( Xanthium canadense Mill . and Xanthium sibiricum Patrin ex Widder ) was established. Volatile organic compounds (VOCs), polar metabolites, and fatty acids were classified by integrated sample preparation, which allowed a broad range for the detection of metabolites simultaneously. Gas chromatography-mass spectrometry (GC-MS) followed by a multivariate statistical analysis was employed to characterize the chemical compositions and subsequently to discriminate between the two species. The results demonstrate that the two species possess obviously diverse chemical characteristics of three different classifications, and discriminant analysis was successfully applied to a number of chemical markers that could be used for the discrimination of the two species. Additional quantitative results for the selected chemical markers consistently showed significant differences between the two species., Competing Interests: The authors declare no conflict of interest.

The objective of this study was to determine the concentrations, potential sources and evaluate the risks of heavy metals in selected plants from Awash River Basin, Ethiopia. A total of 57 samples were analyzed from four different plant species. Microwave-assisted digestion was applied to digest the samples and the concentration of nine elements namely: Al, Cr, Ni, Cu, Zn, As, Cd, Hg, and Pb were analyzed using Inductively Coupled Plasma-Mass Spectrometry (ICP- MS) (Thermos X SERIES2). The obtained data were analyzed using Statistical Package for Social Sciences (SPSS IBM version 20). The recorded mean concentration of heavy metals in the plants were 1.934, 0.023, 0.023, 0.045, 0.129, ND, 0.025, ND, and 0.009 mg/kg in Xanthium strumarium L.(Asteraceae); 0.834, 0.036, 0.024, 0.021, 0.090, ND, 0.002, 0.001, and 0.006 mg/kg in Ficus exasperata Vahl (Moraceae); 1.603, 0.018, 0.019, 0.025, 0.133, 0.005, 0.006, 0.002, and 0.012 mg/kg in Persicaria attenuata (R.Br) Sojak (Polygonaceae); and 0.557, 0.010, 0.010, 0.024, 0.098, ND, 0.012, 0.020, and 0.004 mg/kg in Kanahia laniflora (Forssk.) R.Br. (Asclepiadaceae) for Al, Cr, Ni, Cu, Zn, As, Cd, Hg, and Pb, respectively. Pearson's correlation analysis indicated that there was a strong positive correlation between Al-Ni (r = 0.927 **) and Zn-Cu (r = 0.764 **) at α = 0.01 significant level. Principal component analysis (PCA) indicated that the sources of heavy metals in the plants were associated with anthropogenic factors. The mean concentrations of all elements except Cd in Xanthium strumarium L. (Asteraceae) and Pb in Ficus exasperata Vahl (Moraceae) were below the permissible limit of FAO/WHO (2001 /2005).

Background: Fungal infection with opportunistic fungi can cause a serious problem for immunocompromised persons such as organ-transplant recipients, cancer, and HIV/AIDS patients. Control of these organisms using natural products is an interesting strategy to avoid the use of heavy chemotherapy in patients., Objective: This study aimed to use the extract of Forsskaolea tenacissima L. and Xanthium spinosum L. to suppress the growth of Candida albicans and Geotrichum candidum and to investigate their potential mode of action., Materials and Methods: Different plant extracts were tested for their antifungal activity using disc diffusion method and their mode of action was explored using the scanning electron microscopy (SEM) and gas chromatography-mass spectrometry (GC-MS)., Results: The results showed that chloroform extract of X. spinosum was the most effective against G. candidum, inhibiting its growth at very low concentration (38μg/mL). Chloroform extract of F. tenacissima was the most effective against C. albicans, with a minimum inhibitory concentration of 39μg/mL. SEM demonstrated the fungitoxicity of the plant extracts against both pathogens. C. albicans treated with plant extract were invaginated and ruptured and the treated mycelia of G. candidum were distorted and squashed. GC-MS analysis showed that the chloroform extract of both plants had 13 different compounds., Conclusion: Due to these promising results, these extracts should be further investigated and tested on different strains of C. albicans and G. candidum towards validation of their efficacy as a natural drug., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Xanthium strumarium is an annual pseudometallophyte. To reveal the mechanisms of this species to adapt to metallicolous environmental conditions, phenological traits and biomass allocation of metallicolous and non-metallicolous populations of X. strumarium under six Mn 2+ concentrations by pot culture experiments were performed. The results showed that both time to bolting and time to fruit setting in the metallicolous population were earlier than those in the non-metallicolous population. The number of flowers, fruits, seeds and 1000-seed weight in the metallicolous population were higher than those in the non-metallicolous population under Mn stress. Reproductive allocation and harvest index in the metallicolous population were higher than those in the non-metallicolous population. Furthermore, all the Mn concentrations in leaves, stems, roots, and fruits of the metallicolous population were higher than the counterparts of non-metallicolous population. These results suggested that metallicolous population had higher tolerance to Mn stress than non-metallicolous population, the earlier flowering and fruiting, and the enhancement in reproductive allocation may contribute to plant tolerance to Mn toxicity for X. strumarium., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Colorectal cancer is one of the most common malignancies worldwide and is associated with high mortality rates. We previously reported that Xanthium strumarium L. induces mitotic arrest in proliferating cells, a process mediated by xanthatins., Hypothesis/aim: The aim of this work is to study if xanthatins, isolated from X. strumarium total extract, affect the proliferative capacity of CT26WT colon cancer cells and, in consequence, if tumor growth and proliferation of (lung) metastatic sites can also be arrested in vivo., Study Design: This study consisted of both in vitro and in vivo experiments involving the CT26WT cell line and a subcutaneous mouse model of colon cancer. In vitro cell cycle progression, in vivo tumoral growth and anti-metastatic activity were analyzed to investigate whether xanthatins of X. strumarium induce mitotic arrest in proliferating colorectal carcinoma., Results: Our in vitro results show that X. strumarium, mediated by xanthatins, induces G 2 /M arrest and impair anaphase entrance. This leads to a significant induction of apoptotic and necrotic in CT26WT cells, demonstrating their significant anti-proliferative activity through interfering with the mitotic apparatus. Furthermore, our in vivoresults reveal that X. strumarium inhibits both tumor growth and metastasis progression., Conclusion: X. strumarium antitumor activities are mainly mediated by xanthatins through inhibition of tumor growth and metastasis, inducing mitotic arrest and apoptosis in colon carcinoma cells. These findings further confirm the therapeutic potential of X. strumarium in colorectal cancer., (Copyright © 2018. Published by Elsevier GmbH.)

This study significantly aims to analyze the effect of CFX coated gold nanoparticles on the allergic rhinitis in mouse model. Female BALB/C mice were intraperitoneally injected with ovalbumin and aluminum hydroxide in order to sensitize on 0th, 7th, 14th, and 21st day. Nano‑gold was also nasally inoculated earlier to the intranasal administration of OVA. The acuteness of allergic rhinitis was evaluated based on the nasal indications, interleukin IL-4, and interferon (INF)-γ levels present in the NLF of mice. Also, Hematoxylin-eosin as well as Schiff-periodic acid stain assays were carried out to briefly investigate the histological modifications in the sensitized mice. Nano‑gold reduced the incidence of nasal symptoms as well as minimized the IL-4 production, no impact was showed over the levels of INF-γ. Further, the extent of inflammatory cell intrusion was also influenced by the CFX/AuNPs. These experimental findings manifested that AuNPs may considerably inhibit the allergic inflammation in mice models and may be expected to serve as anti-allergic rhinitis agents., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Two new diterpenoid glycosides, fructusnoids D (1) and E (2), and two new monoterpenoid glycosides (3, 4), together with three known diterpenoid glycosides (5-7) and three known monoterpenoid glycosides (8-10), were isolated from the fruits of Xanthium chinense. Their structures were elucidated by spectrometric analyses.

The essential oil (EO) of Xanthium strumarium L. leaves (family: Asteraceae) was extracted by hydrodistillation, and then analyzed by gas chromatography-mass spectrometry (GC-MS). Forty-three essential compounds were identified. The sesquiterpenoids represented the major constituents (72.4%), including oxygenated (61.78%) and non-oxygenated (10.62%) sesquiterpenes, followed by monoterpenes (25.19%). The diterpenoids and oxygenated hydrocarbons were determined as minor compounds. The main constituents of the EO were 1,5-dimethyltetralin (14.27%), eudesmol (10.60%), l-borneol (6.59%), ledene alcohol (6.46%), (-)-caryophyllene oxide (5.36%), isolongifolene, 7,8-dehydro-8a-hydroxy (5.06%), L-bornyl acetate (3.77%), and aristolene epoxide (3.58%). A comparative analysis was stated here between the EO of Egyptian X. strumarium and those previously reported from Pakistan, Iran, and Brazil based on chemometic tools such as principal components analysis (PCA) and agglomerative hierarchical clustering (AHC). The EO of X. strumarium showed weak 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity with IC 50 321.93 µL / L -1 , which was comparable to ascorbic acid as a reference. However, the EO exhibited significant allelopathic potential regarding the germination and growth of the noxious weed Bidens pilosa in a concentration-dependent manner. Therefore, further study is recommended to characterize the EO from X. strumarium as an eco-friendly green bioherbicide against weeds, as well as determine their mode of actions.

Xanthium strumarium L. (Asteraceae) is a common and well-known traditional Chinese herbal medicine usually named Cang-Er-Zi, and has been used for thousands of years in China. The purpose of this paper is to summarize the progress of modern research, and provide a systematic review on the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the X. strumarium . Moreover, an in-depth discussion of some valuable issues and possible development for future research on this plant is also given. X. strumarium , as a traditional herbal medicine, has been extensively applied to treat many diseases, such as rhinitis, nasal sinusitis, headache, gastric ulcer, urticaria, rheumatism bacterial, fungal infections and arthritis. Up to now, more than 170 chemical constituents have been isolated and identified from X. strumarium , including sesquiterpenoids, phenylpropenoids, lignanoids, coumarins, steroids, glycosides, flavonoids, thiazides, anthraquinones, naphthoquinones and other compounds. Modern research shows that the extracts and compounds from X. strumarium possess wide-ranging pharmacological effects, including anti- allergic rhinitis (AR) effects, anti-tumor effects, anti-inflammatory and analgesic effects, insecticide and antiparasitic effects, antioxidant effects, antibacterial and antifungal effects, antidiabetic effects, antilipidemic effects and antiviral effects. However, further research should focus on investigating bioactive compounds and demonstrate the mechanism of its detoxification, and more reasonable quality control standards for X. strumarium should also be established.

The aim of this study was to identify bioactive compounds from leaves of the invasive plant Xanthium spinosum and assess their phytotoxic activity. Activity-guided fractionation led to the isolation of 6 bioactive compounds: xanthatin ( 1 ), 1α,5α-epoxyxanthatin ( 2 ), 4-epiisoxanthanol ( 3 ), 4-epixanthanol ( 4 ), loliolide ( 5 ) and dehydrovomifoliol ( 6 ). Of them, compounds 2 ⁻ 6 were isolated from the X. spinosum for the first time. The structures of 1 ⁻ 6 were elucidated on the basis of extensive NMR studies and ESI-MS measurements as well as comparison with literature data. All of compounds were evaluated for their phytotoxic activity. Among them, compounds 1 ⁻ 4 exhibited stronger activity on 2 receiver plants compared with the other 2 compounds, with xanthatin ( 1 ) being the most potent compound, which suppressed root growth of the dicot plant Amaranthus retroflexus by 32.5%, 39.4%, 84.7% when treated xanthatin ( 1 ) at 5, 20, and 100 µg/mL, while for the monocot plant, root growth was inhibited by 14.7%, 28.0%, and 40.0%, respectively. Seedling growth was nearly completely inhibited when the concentration of xanthanolides increased to 500 µg/mL, whereas there was still some seedling growth when loliolide ( 5 ) and dehydrovomifoliol ( 6 ) were applied at the same concentration. Dehydrovomifoliol ( 6 ) did not negatively affect seedling growth of P. annua at all tested concentrations, and root length was still 42.0% of the control when the highest concentration 500 µg/mL was used. This is the first report of the phytotoxicity of 1α,5α-epoxyxanthatin ( 2 ), 4-epiisxanthanol ( 3 ) and 4-epixanthanol ( 4 ). These compounds have the potential to be utilized as natural herbicides, especially 4-epiisoxanthanol ( 3 ), which exhibited significant selective activity between the dicot and monocot plants. On the other hand, whether these bioactive substances serve as allelochemicals to facilitate the invasion success of X. spinosum needs to be further studied.

Xanthatin (XT), a naturally occurring sesquiterpene lactone presented in cocklebur ( Xanthium strumarium L.), is under development as a potential anticancer agent. Despite the promising anticancer effect of XT, the molecular mechanism underlying its cellular action has not been well elucidated. The mammalian thioredoxin reductase (TrxR) enzymes, the essential seleno-flavoproteins containing a penultimate selenocysteine (Sec) residue at the C-terminus, represent a promising target for cancer chemotherapeutic agents. In this study, XT inhibits both the purified TrxR and the enzyme in cells. The possible binding mode of XT with the TrxR protein is predicted by the covalent docking method. Mechanism studies reveal that XT targets the Sec residue of TrxR and inhibits the enzyme activity irreversibly. Simultaneously, the inhibition of TrxR by XT promotes the oxidative stress-mediated apoptosis of HeLa cells. Importantly, the knockdown of the enzyme sensitizes the cells to XT treatment. Targeting TrxR thus discloses a novel molecular mechanism in accounting for the cellular action of XT and provides insights into the development of XT as an anticancer agent.

This project is to investigate lignans from the dried fruits of Xanthium sibiricum (Xanthii Fructus). The chemical constituents were extract by 70% ethanol and isolated by silica gel, ODS, Sephadex LH-20, MCI column chromatography. Based on comparison of their spectral data with those reported in literature, they were elucidated as (-)-pinoresinol (1), balanophonin A (2), diospyrosin (3), dehydrodiconiferyl alcohol (4), 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol (5), (-)-simulanol (6), (-)-7R,8S-dehydrodiconiferyl alcohol (7), chushizisin E (8), dihydrodehydrodiconiferyl alcohol (9), 7R,8S-dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (10), erythro-1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (11), leptolepisol D (12), 8-O-4' neolignan 4-O-β-glucopyranoside (13), (-)-1-O-β-D-glucopyranosyl-2-{2-methoxy-4-[1-(E)-propen-3-ol]phenoxyl}-propane-3-ol(14), 1-(4-hydroxy-3-methoxy)-phenyl-2-[4-(1,2,3-trihydroxypropyl)-2-methoxy]-phenoxy-1,3-propandiol (15), threo-dihydroxy dehydrodiconiferyl alcohol (16), (-)-(2R)-1-O-β-D-glucopyranosyl-2-{2-methoxy-4-[(E)-formylviny1]phenoxyl} propane-3-ol (17). Compound 2-17 were isolated from the genus Xanthium for the first time. Compound 1 were isolated form Xanthii Fructus for the first time., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Through the methods of polyamide resin， Sephadex LH-20， ODS column chromatography and preparative HPLC etc.， 7 compounds were isolated from the 70% ethanol extract of the fruits of Xanthium chinense. Based on ESI-MS and NMR data， the structures of these compounds were identified as pungiolide O(1)， grasshopper ketone(2)， icariside F₂(3)， 7-[(β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl)oxymethy]-8，8-dimethyl-4，8-dihydrobenzo[1，4]thiazine-3，5-dione(4)，(6R，9S)-3-oxo-α-ionol β-D-glucopyranoside(5)， cryptochlorogenic acid methyl ester(6)， and chlorogenic acid methyl ester(7). Among them， compound 1 is a new compound., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii Fructus) have been widely used in raw and processed forms to achieve different therapeutic effects in practice. In this study, a comprehensive strategy was proposed for evaluating the active components in 30 batches of raw and processed Xanthii Fructus (RXF and PXF) samples, based on high-performance liquid chromatography coupled with photodiode array detection (HPLC-PDA). Twelve common peaks were detected and eight compounds of caffeoylquinic acids were simultaneously quantified in RXF and PXF. All the analytes were detected with satisfactory linearity (R² > 0.9991) over wide concentration ranges. Simultaneously, the chemically latent information was revealed by hierarchical cluster analysis (HCA) and principal component analysis (PCA). The results suggest that there were significant differences between RXF and PXF from different regions in terms of the content of eight caffeoylquinic acids. Potential chemical markers for XF were found during processing by chemometrics., Competing Interests: The authors have no conflicts of interest to declare.

The antiplasmodial active extract of Xanthium cavanillesii contains 3,4-dicaffeoyl quinic acid (3,4-DCQA), 3,5-dicaffeoyl quinic acid (3,5-DCQA) and 1,3,5-tricaffeoyl quinic acid (1,3,5-TCQA). These results inspired us to investigate the interaction of these molecules with a promising validated target of Plasmodium, PfATP6 orthologue of mammalian Ca +2 -ATPase. Models of this receptor were obtained through comparative modelling. Afterwards, molecular docking studies were used to identify possible interaction modes of these caffeoyl quinic derivatives on the binding site. The 1,3,5-TCQA had the best energy, but all of these had better energy than thapsigargin, a non-competitive inhibitor of the sarco/endoplasmatic reticulum Ca +2 -ATPase (SERCA).

The fruits of Xanthium sibiricum Patr yielded five phenylpropanoid derivatives, named as xanthiumnolics A-E (1-5). Their structures were elucidated by spectroscopic analysis and comparison with literature data. The isolated ones were tested for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7, and compound 5 showed strong inhibitory activities with IC 50 value of 8.73μM., (Copyright © 2016. Published by Elsevier B.V.)

Xanthium spinosum L. is a highly invasive plant originated from South America throughout the world as well as in Corsica Island. The chemical composition of X. spinosum essential oils from 25 Corsican locations was investigated using GC-FID and GC/MS. Seventy-four components, which accounted for 96.2% of the total amount, were reported for the first time in the essential oil from aerial parts. The main compounds were eudesma-4(14),7-dien-1β-ol (61; 21.3%), germacrene D (36; 8.8%) and cadalene (60; 8.7%). Comparison with the literature highlighted the originality of the Corsican essential oil and eudesma-4(14),7-dien-1β-ol could be used as taxonomical marker to the systematics of the Xanthium genus. The essential oils obtained from separate organs and during the plant vegetative cycle were also studied to gain more knowledge about the correlations between the volatile production and the phenological states of this weed. The production of oxygenated sesquiterpenes was predominant during the plant-flowering process. The study focuses on direct correlation between the chemical composition of individual 25 oil samples and the morphological differences of the plant. Our results have gained more knowledge about the secondary metabolite production that occurs during the plant life, they could be interesting in order to manage the dispersal of X. spinosum., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Xanthium strumarium L. is a member of the Asteraceae family popularly used with multiple therapeutic purposes. Whole extracts of this plant have shown anti-mitotic activity in vitro suggesting that some components could induce mitotic arrest in proliferating cells., Aim of the Sudy: Aim of the present work was to characterize the anti-mitotic properties of the X. strumarium whole extract and to isolate and purify active molecule(s)., Materials and Methods: The capacity of the whole extract to inhibit mitotic progression in mammalian cultured cells was investigated to identify its anti-mitotic activity. Isolation of active component(s) was performed using a bioassay-guided multistep separation procedure in which whole extract was submitted to a progressive process of fractionation and fractions were challenged for their anti-mitotic activity., Results: Our results show for the first time that X. strumarium whole extract inhibits assembly of the mitotic spindle and spindle-pole separation, thereby heavily affecting mitosis, impairing the metaphase to anaphase transition and inducing apoptosis. The purification procedure led to a fraction with an anti-mitotic activity comparable to that of the whole extract. Chemical analysis of this fraction showed that its major component was xanthatin., Conclusions: The present work shows a new activity of X. strumarium extract, i.e. the alteration of the mitotic apparatus in cultured cells that may be responsible for the anti-proliferative activity of the extract. Anti-mitotic activity is shown to be mainly exerted by xanthatin., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Nine dimeric xanthanolides, pungiolides F-N, and five known analogues, pungiolides A-E, were isolated from fruits of Xanthium chinense. Their structures were elucidated through spectroscopic and electronic circular dichroism (ECD) analyses. Pungiolide F is a xanthanolide dimer with an acyclic linkage. Five of the dimers, pungiolides H, L, A, C and E, exhibited moderate cytotoxicities with IC 50 values in the range of 0.90-6.84 μM using taxol as the positive control, which had, by comparison, IC 50 values in the range of 0.00118-0.0675 μM. These findings enrich the structural diversity of dimeric sesquiterpene lactones., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The sesquiterpene lactones xanthanodiene, 4-epi-xanthanol, 4-epi-isoxanthanol, and 4-epi-xanthinin, as well as the xanthanolide derivative 4-oxo-bedfordia acid were isolated from the chloroform extracts of roots and flowers of Xanthium cavanillesii Schouw. The identities of these compounds were corroborated through comparison of their spectroscopic data, including IR, MS, and (1)H and (13)C NMR assignments, with literature reports. In addition, the structural characterization of 4-oxo-bedfordia acid was revisited and a comprehensive spectroscopic study of the compound is presented. This is to our knowledge the first phytochemical investigation of the roots of X. cavanillesii, and of flowers in the whole Xanthium genus.

Shiga toxin-producing Escherichia coli (STEC) serotype O157:H7 is one of the most important human pathogenic microorganisms, which can cause life-threatening infections. Xanthium strumarium L. is a plant with anti-bacterial activity against gram-negative and gram-positive bacteria. This study aims to demonstrate in vitro efficacy of the essential oil (EO) extracted from Xanthium strumarium L. against E. coli O157:H7. Using the agar test diffusion, the effect of Xanthium strumarium L. EO (5, 10, 15, 30, 60, and 120 mg/mL) was verified at each of the four different growth phases of E. coli O157:H7. Cell counts of viable cells and colony forming unit (CFU) were determined at regular time points using Breed's method and colony counting method, respectively. No viable cell was detectable after the 1 hour-exposure to X. strumarium EO at 30, 60, and 120 mg/mL concentrations. No bacterial colony was formed after 1 h until the end of the incubation period at 24 h. At lower concentrations, the number of bacteria cells decreased and colonies could be observed only after incubation. At the exponential phase, the EO at 15 mg/mL was only bacteriostatic, while from 30 mg/mL started to be bactericidal. X. strumarium EO antibacterial activity against Shiga toxin-producing E. coli O157:H7 is dependent on EO concentration and physiological state of the microorganisms tested. The best inhibitory activity was achieved during the late exponential and the stationary phases.

Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1β (PTP1β), advanced glycation end products (AGEs), and ABTS⁺ radical scavenging activity using in vitro assays. Among the isolated compounds, methyl-3,5-di-caffeoyquinic acid exhibited significant inhibitory activity against α-glucosidase (18.42 μM), PTP1β (1.88 μM), AGEs (82.79 μM), and ABTS⁺ (6.03 μM). This effect was marked compared to that of the positive controls (acarbose 584.79 μM, sumarin 5.51 μM, aminoguanidine 1410.00 μM, and trolox 29.72 μM respectively). In addition, 3,5-di-O-CQA (88.14 μM) and protocatechuic acid (32.93 μM) had a considerable inhibitory effect against α-glucosidase and ABTS⁺. Based on these findings, methyl-3,5-di-caffeoyquinic acid was assumed to be potentially responsible for the anti-diabetic actions of X. strumarium.

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-β1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-β1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-β1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-β1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-β1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17., Competing Interests: The authors declare no conflict of interest.

Xanthatin, a xanthanolide sesquiterpene lactone isolated from Xanthium strumarium L. (Asteraceae), has prominent anti-tumor activity. Initial mechanism of action studies suggested xanthatin triggered activation of Wnt/β-catenin. We examined the effects of xanthatin on signaling pathways in A459 lung cancer cells and mouse embryonic fibroblasts to ascertain requirements for xanthatin-induced cell death and tumor growth in xenografts. Genetic inactivation of GSK-3β, but not the related isoform GSK-3α, compromised xanthatin cytotoxicity while inactivation of β-catenin enhanced xanthatin-mediated cell death. These data provide insight into how xanthatin and related molecules could be effectively targeted toward certain tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Xanthium strumarium L. (Asteraceae) has traditionally been used to treat bacterial infections, nasal sinusitis, urticaria, arthritis, chronic bronchitis and rhinitis, allergic rhinitis, edema, lumbago, and other ailments. However, the molecular mechanisms by which this plant exerts its anti-inflammatory effects are poorly characterized. Here we studied the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Xs-ME) and validated its pharmacological targets., Materials and Methods: To evaluate the anti-inflammatory activity of Xs-ME, we employed lipopolysaccharide (LPS)-treated macrophages and an HCl/EtOH-induced mouse model of gastritis. We also used HPLC to identify the potentially active anti-inflammatory components of this extract. The molecular mechanisms of its anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes., Results: The production of nitric oxide (NO) and prostaglandin E2 (PGE2) were both suppressed by Xs-ME. Moreover, orally administered Xs-ME ameliorated HCl/EtOH-induced gastric lesions. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signaling events upstream of NF-κB translocation, such as phosphorylation of AKT and the formation of PDK1-AKT signaling complexes, were also inhibited by Xs-ME. Moreover, Xs-ME suppressed the enzymatic activity of PDK1. Additionally, PDK1-induced luciferase activity and Akt phosphorylation were both inhibited by Xs-ME. We also identified the polyphenol resveratrol as a likely active anti-inflammatory component in Xs-ME that targets PDK1., Conclusion: Xs-ME exerts anti-inflammatory activity in vitro and in vivo by inhibiting PDK1 kinase activity and blocking signaling to its downstream transcription factor, NF-κB., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)