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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.)

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.

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.

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 (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.

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.)

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.

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.

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.

The leaves of the Xanthium spinosum plant have been used culturally in Paraguay for their medicinal properties. Acute toxicity of mature leaf extract was evaluated. For the study, 35 Balb/c mice were selected and allocated into 7 groups, 6 test groups and 1 control group. The extract was prepared in concentrations of 6% and 9% (g/dL). The 6% concentration was administrated to 3 test groups and 9% concentration to the remaining 3 groups, with doses between 200 and 1000 mg/kg per mouse. After 14 days of observation, blood samples were taken for laboratory studies of urea and transaminases and organs were examined for pathological studies. There were increased levels of GOT and urea in the test groups compared to the control group. In conclusion, the consumption of mature leaf extract of Xanthium spinosum can cause hepatic damage.

Background: Although toxic, the Chinese medicinal herb Xanthii Fructus (XF) is commonly used to treat traditional Chinese medicine (TCM) symptoms that resemble cold, sinusitis and arthritis. According to TCM theory, stir-baking (a processing method) can reduce the toxicity and enhance the efficacy of XF., Methods: Cytotoxicities of raw XF and processed XF (stir-baked XF, SBXF) were determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in normal liver derived MIHA cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression were measured by the Griess reagent and quantitative real-time PCR, respectively. The chemical profiles of XF and SBXF were compared using an established ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method., Results: SBXF was less toxic than XF in MIHA cells. Both XF and SBXF had anti-inflammatory effects as demonstrated by their abilities to reduce nitric oxide production as well as inducible nitric oxide synthase mRNA expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Interestingly, the anti-inflammatory effects of SBXF were more potent than that of XF. By comparing the chemical profiles, we found that seven peaks were lower, while nine other peaks were higher in SBXF than in XF. Eleven compounds including carboxyatractyloside, atractyloside and chlorogenic acid corresponding to eleven individual changed peaks were tentatively identified by matching with empirical molecular formulae and mass fragments, as well as literature data., Conclusion: Our study showed that stir-baking significantly reduced the cytotoxicity and enhanced the anti-inflammatory effects of XF; moreover, with a developed ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry method we differentiated XF and SBXF by their chemical profiles. Further studies are warranted to establish the relationship between the alteration of chemical profiles and the changes of medicinal properties caused by stir-baking.

The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices. In total, 34 compounds were identified, accounting for 98.96% of the EO. The main compounds in the EO were cis-β-guaiene (34.2%), limonene (20.3%), borneol (11.6%), bornyl acetate (4.5%), β-cubebene (3.8%), sabinene (3.6%), phytol (3.1%), β-selinene (2.8%), camphene (2.2%), α-cubebene (2.4%), β-caryophyllene (1.9%), α-pinene (1.8%) and xanthinin (1.04%). The antibacterial and antifungal screening of the EO showed that all assayed concentrations significantly inhibited the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger (MIC = 0.5 ± 0.1, 1.3 ± 0.0, 4.8 ± 0.0, 20.5 ± 0.3, 55.2 ± 0.0 and 34.3 ± 0.0 µg/mL, respectively). The scolicidal assay indicated that the EO exhibited a significant activity against E. granulosus protoscolices. To the best of our knowledge, this is the first report on the scolicidal activity of X. strumarium. Because of the emergence of antimicrobial drug resistance, the study of new effective natural chemotherapeutic agents, such as the X. strumarium EO, possibly with low side effects, represents a very promising approach in biomedical research.

Xanthanolides from Xanthium strumarium L. exhibit various pharmacological activities and these compounds are mainly produced in the glandular trichomes of aerial plant parts. The regulation of xanthanolide biosynthesis has never been reported in the literature. In this study, the effects of phytohormonal stimulation on xanthumin (a xanthanolide compound) biosynthesis, glandular trichomes and germacrene A synthase (GAS) gene expression in X. strumarium L. young leaves were investigated. The exogenous applications of methyl jasmonate (MeJA), indole-3-acetic acid (IAA), and gibberrellin A3 (GA3) at appropriate concentrations were all found to improve xanthumin biosynthesis, but in different ways. It was suggested that a higher gland density stimulated by MeJA (400 µM) or IAA (200 µM) treatment caused at least in part an improvement in xanthumin production, whereas GA3 (10 µM) led to an improvement by up-regulating xanthumin biosynthetic genes within gland cells, not by forming more glandular trichomes. Compared to the plants before the flowering stage, plants that had initiated flowering showed enhanced xanthumin biosynthesis, but no higher gland density, an effect was similar to that caused by exogenous GA3 treatment.

The fruits of Xanthium strumarium L. (Asteraceae) have been used extensively in China for treatment of various diseases such as allergic rhinitis (AR), tympanitis, urticaria and arthritis or ozena. This study was designed to systemically investigate the effects of the caffeoylxanthiazonoside (CXT) isolated from fruits of X. strumarium on AR in rodent animals. Animals were orally administered with CXT. Anti-allergic activity of CXT was evaluated by passive cutaneous anaphylaxis test (PCA); acetic acid-induced writhing tests were used to evaluate the analgesic effects of CXT; acetic acid-induced vascular permeability tests were performed to evaluate anti-inflammatory effect of CXT. Then, the model AR in rats was established to evaluate the effects of CXT on AR with the following tests: the sneezing and nasal scratching frequencies, IgE level in serum, and histopathological examinations. Our results demonstrated that CXT had favorable anti-allergic, anti-inflammatory and analgesic effects. Additionally, we found that CXT was helpful to ameliorate the nasal symptoms and to down-regulate IgE levels in AR rats. Thus, we suggested that CXT can be treated as a candidate for treating AR., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

In present study, the anti-inflammatory potential of three medicinal plants, Xanthium strumarium, Achyranthes aspera and Duchesnea indica were evaluated, using both in vitro and in vivo assays. Carrageenan induced hind paw edema model was used to carry out the in vivo anti-inflammatory activity, while for in vitro screening lipoxygenase inhibition assay was used. Crude extract of all the selected plants depicted significant (plt;0.001) anti-inflammatory activity, at late phase of inflammation. Achyranthes aspera also showed considerable anti-inflammatory activity (47%) at relatively lower concentration (200 mg/ml), at the initial phase of inflammation. Similarly the ethyl acetate fraction of all the selected plants showed significant lipoxygenase inhibition activity when compared with the standard drug (Baicalein). The results obtained from both in vitro and in vivo anti-inflammatory activity suggest that the ethyl acetate fraction of the crude extract of all the selected plants can be used for the isolation of new lead compounds with better anti-inflammatory activity.

Background and Aims: Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant-herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field., Methods: Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness., Key Results: The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide., Conclusions: To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing extensive stereochemical variation.

Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25-100 μg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations.

Background: Xanthium indicum stem is used in folk medicine of Bangladesh to control sugar in diabetic patients and to alleviate pain. The objective of the study was to evaluate antihyperglycemic and antinociceptive activity of methanolic extract of Xanthium indicum stems (XISE) in mice., Methods: Antihyperglycemic activity was measured by oral glucose tolerance tests in glucose-loaded Swiss albino mice. Antinociceptive activity was determined by observed decreases in abdominal constrictions in acetic acid-induced gastric pain model in mice., Results: The methanol extract of stems showed dose-dependent and statistically significant antihyperglycemic activity at doses of 50, 100, 200 and 400 mg per kg body weight (p values, respectively, < than 0.01, 0.01, 0.005, and 0.01). Highest reduction in blood glucose level (31.2%) was observed with the highest dose (400 mg) of the extract. A standard antihyperglycemic drug, glibenclamide, reduced blood glucose levels by 46.2%, when administered at a dose of 10 mg per kg body weight. In antinociceptive activity tests, the extract when administered at the aforementioned four doses, reduced the number of abdominal constrictions in mice, respectively, by 41.7, 50.0, 54.2, and 61.0%. In comparison, a standard antinociceptive drug, aspirin, when administered at a dose of 200 mg per kg body weight, reduced the number of abdominal constrictions by 37.5%., Conclusion: The experimental results obtained in the present study validate the use of X. indicum stems in folk medicines of Bangladesh to lower blood sugar in diabetic patients and to alleviate pain.

Four new glycosides, namely 3β-norpinan-2-one 3-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (1), (6Z)-3-hydroxymethyl-7-methylocta-1,6-dien-3-ol 8-O-β-d-glucopyranoside (2), (6E)-3-hydroxymethyl-7-methylocta-1,6-dien-3-ol 8-O-β-d-gluco-pyranoside (3), and 7-[(β-d-apiofuranosyl-(1→6)-β-d-glucopyranosyl)oxymethy]-8,8-dimethyl-4,8-dihydrobenzo[1,4]thiazine-3,5-dione (4), were isolated from the fruits of Xanthium sibiricum Patr together with three known compounds, xanthiside (5), adenosine (6), and 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (7). The structures of the new compounds were determined on the basis of detailed spectroscopic analyses.

Xanthanolides, as the sesquiterpene lactones, are reportedly the major components for the pharmacological properties of X. strumarium L. species. Phytochemical studies indicated that the glandular structures on the surface of plant tissues would form the primary sites for the accumulation of this class of the compounds. As the interface between plants and their natural enemies, glandular trichomes may vary with respect to which of their chemicals are sequestered against different herbivores in different ecologies. However, to date, no data are available on the chemical characterisation of X. strumarium glandular cells. In this study, the trichome secretions of the X. strumarium species originating from nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC-ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium glandular trichomes were discovered along with the qualitative and quantitative evaluations of their presence of xanthanolides; these were designated glandular cell Types I, II, and III, respectively. The main xanthanolides in Type I cells were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8-epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of each being present. For Type III cells, significantly higher concentrations of 8-epi-xanthatin or xanthinosin (relative to xanthatin) were detected with xanthinosin only being observed in this type. Further research will focus on understanding the ecological and molecular mechanism causing these chemotype differences in X. strumarium glandular structures.

Anti-cancer investigations on Xanthatin mainly focus on in vitro experiments. We herein reported the anti-tumor effects of Xanthatin both in vitro and in vivo. MTS assay results showed that Xanthatin had a remarkable anti-proliferative effect on B16-F10 cells. Moreover, the expression of β-catenin was up-regulated both in vitro and in vivo. Animal studies further revealed that Xanthatin killed the tumor cells around the blood vessels which contributes to reduce microvascular density extremely. All these results indicate that Xanthatin inhibited murine melanoma B16-F10 cell proliferation possibly associated with activation of Wnt/β-catenin pathway and its activity against melanoma tumor might also be relevant to inhibition of angiogenesis., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Xanthium strumarium L. (Asteraceae) is traditionally used in Korea to treat skin diseases. In this study, we investigated the effects of a X. strumarium stem extract on melanin synthesis. It inhibited melanin synthesis in a concentration-dependent manner, but it did not directly inhibit tyrosinase, the rate-limiting melanogenic enzyme, and instead downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase expression. MITF, the master regulator of pigmentation, is a target of the Wnt signaling pathway, which includes glycogen synthase kinase 3β (GSK3β) and β-catenin. Hence, the influence of X. strumarium stem extract on GSK3β and β-catenin was further investigated. X. strumarium induced GSK3β phosphorylation (inactivation), but the level of β-catenin did not change. Moreover, a specific GSK3β inhibitor restored X. strumarium-induced melanin reduction. Hence, we suggest that X. strumarium inhibits melanin synthesis through downregulation of tyrosinase via GSK3β phosphorylation.

The present study describes the ethnobotanical, phytochemical, and toxicological evaluations of Xanthium strumarium L. growing in Bangladesh. In toxicity evaluation on rats, the methanol extract of seedlings showed mortality, while both seedling and mature plant extracts raised the serum alanine transaminase and aspartate transaminase values and produced significant abnormalities in the histopathology of liver and kidney of rats. On the other hand, the aqueous soluble fraction of methanol extract of mature plant (LC50 = 0.352 microg/mL) and methanol crude extract of seedlings (LC50 = 0.656 microg/mL) demonstrated significant toxicity in the brine shrimp lethality bioassay. A total of four compounds were purified and characterized as stigmasterol (1), 11-hydroxy-11-carboxy-4-oxo-1(5),2(Z)-xanthadien-12,8-olide (2), daucosterol (3) and lasidiol-10-anisate (4). The present study suggests that X. strumarium is toxic to animal.

Cytokines released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes. Interleukin (IL)-1beta and interferon (IFN)-gamma are the primary cytokines responsible for stimulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, which leads to beta-cell damage. In addition, nuclear factor-kappaB (NF-kappaB) plays a crucial role in the activation of this pathway. Therefore, suppression of the cytokine-NF-kappaB pathway is considered an effective therapeutic strategy for preventing inflammatory reactions in pancreatic beta-cells. In this study, the effects of Fructus Xanthii extract (FXE) on IL-1beta and IFN-gamma-induced beta-cell damage were examined. Treatment of RINm5F cells with IL-1beta and IFN-gamma reduced cell viability, however, FXE completely protected cells from IL-1beta and IFN-gamma-mediated reduction in viability in a concentration-dependent manner. In addition, incubation with FXE resulted in a significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, which correlated with the reduced levels of the inducible form of iNOS mRNA and protein observed. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p50 subunit levels in the nucleus, as well as increased IkappaBalpha degradation in cytosol when compared to unstimulated cells, which indicates that the mechanism by which FXE inhibited the iNOS gene involves inhibition of NF-kappaB activation. Furthermore, a protective effect of FXE was demonstrated by reduction in NO generation and iNOS expression, as well as the normal insulin secreting responses to glucose observed in IL-1beta and IFN-gamma-treated islets.

The aim of this study was to fractionate an extract of Xanthium strumarium L. (EXS) and to investigate the anti-inflammatory and analgesic properties of the extract and its fractions. The ethanol extract of X. strumarium (EXS) was fractionated on the basis of polarity. Among the different fractions, the n-butanol fraction showed the highest anti-inflammatory activity in the croton-oil-induced ear edema test and furthermore reduced the number of writhings induced by acetic acid in mice in a dose-dependent manner. This indicates that the n-butanol fraction of X. strumarium possesses potent analgesic effects which are likely to be mediated by its anti-inflammatory activity. Bioassay-guided fractionation of EXS led to the isolation and identification of ten caffeoylquinic acids and three heterocyclics by HPLC-DAD-MS(n) from the active n-butanol fraction, implying that the active compounds are polar in nature. The isolated caffeoylquinic acids could partially explain the antinociceptive effect of X. strumarium polar extract.