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1.
Phytochemistry ; 225: 114196, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38936529

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic , Apoptosis , Drug Screening Assays, Antitumor , Fruit , Sesquiterpenes , Xanthium , Xanthium/chemistry , Humans , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Fruit/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Apoptosis/drug effects , Molecular Structure , Structure-Activity Relationship , Cell Proliferation/drug effects
2.
Bioorg Chem ; 150: 107527, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38876005

ABSTRACT

Two protoberberine alkaloids with a unique C28 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.


Subject(s)
AMP-Activated Protein Kinases , Berberine Alkaloids , Fruit , Xanthium , Humans , Fruit/chemistry , Xanthium/chemistry , Berberine Alkaloids/chemistry , Berberine Alkaloids/pharmacology , Berberine Alkaloids/isolation & purification , Hep G2 Cells , Molecular Structure , AMP-Activated Protein Kinases/metabolism , Structure-Activity Relationship , Dose-Response Relationship, Drug , Drug Discovery , Enzyme Activators/pharmacology , Enzyme Activators/chemistry , Enzyme Activators/isolation & purification
3.
J Agric Food Chem ; 71(29): 11239-11251, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37449982

ABSTRACT

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 1H and 13C 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 (IC50 = 1.1 and 24.8 µg/mL, respectively) against the spore of Botrytis cinerea than their precursor xanthatin (IC50 = 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 (IC50 = 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 EC50 values of 2.3, 11.7, 11.1, and 3.0 µg/mL, respectively, whereas the EC50 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.


Subject(s)
Fungicides, Industrial , Sesquiterpenes , Xanthium , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Xanthium/chemistry , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Structure-Activity Relationship , Spores, Fungal , Botrytis , Lactones/pharmacology , Sesquiterpenes/pharmacology , Esters/pharmacology , Oximes/pharmacology
4.
Phytochemistry ; 208: 113603, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36720451

ABSTRACT

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-1ß, and Il-6 mRNA expression induced by lipopolysaccharide in the macrophage cell line RAW264.7. Further investigation showed that xanthsibiriolide and 11ß-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,ß-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.


Subject(s)
Sesquiterpenes , Xanthium , Mice , Animals , Xanthium/chemistry , Polycyclic Sesquiterpenes/analysis , Phosphatidylinositol 3-Kinases , Sesquiterpenes/chemistry , Anti-Inflammatory Agents/pharmacology , Plant Components, Aerial/chemistry , Molecular Structure
5.
Molecules ; 27(23)2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36500229

ABSTRACT

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.


Subject(s)
Xanthium , Xanthium/chemistry , Chemical Fractionation
6.
Molecules ; 27(21)2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36364122

ABSTRACT

Ziniolide, xantholide B (11α-dihydroziniolide), and 11ß-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 1H- and 13C-NMR data of 11ß-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.


Subject(s)
Oils, Volatile , Xanthium , Xanthium/chemistry , Allelopathy , Sesquiterpenes, Guaiane/pharmacology , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Germination , Seedlings , Plant Extracts/pharmacology , Plant Extracts/chemistry
7.
J Asian Nat Prod Res ; 24(10): 925-934, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35899696

ABSTRACT

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 IC50 values of 20.12, 22.89 and 68.66 µM, respectively.


Subject(s)
Sesquiterpenes , Xanthium , Xanthium/chemistry , Fruit/chemistry , Molecular Structure , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Lipopolysaccharides/pharmacology
8.
Toxicon ; 213: 13-22, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35427636

ABSTRACT

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 Ca2+ 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 Ca2+ 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 Ca2+ 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.


Subject(s)
Mitochondrial Permeability Transition Pore , Xanthium , Adenosine Triphosphate/metabolism , Animals , Antidotes , Female , Glucose/metabolism , Isoflavones , Kidney , Liver , Oxidative Stress , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Xanthium/chemistry , Xanthium/metabolism
9.
Acta Biochim Pol ; 69(1): 65-69, 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35129942

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/drug therapy , Osteoarthritis/drug therapy , Plant Extracts/pharmacology , Animals , Arthritis, Experimental/metabolism , Bone and Bones/metabolism , Dinoprostone/metabolism , Disease Models, Animal , Interleukin-6/metabolism , Male , Mice , Nitric Oxide/metabolism , Osteoarthritis/metabolism , Protective Agents/pharmacology , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Sesquiterpenes/pharmacology , Xanthium/chemistry
10.
J Nat Med ; 76(2): 468-475, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34993755

ABSTRACT

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 IC50 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.


Subject(s)
Antineoplastic Agents , Xanthium , Fruit , Phytochemicals/pharmacology , Xanthium/chemistry
11.
Bioorg Med Chem Lett ; 55: 128481, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34852242

ABSTRACT

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 1H NMR, 13C 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 (IC50 = 78.91 µg/mL) and 2o (IC50 = 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.


Subject(s)
Antifungal Agents/pharmacology , Furans/pharmacology , Xanthium/chemistry , Alternaria/drug effects , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Botrytis/drug effects , Colletotrichum/drug effects , Dose-Response Relationship, Drug , Furans/chemical synthesis , Furans/chemistry , Fusarium/drug effects , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
12.
Nat Prod Res ; 36(7): 1820-1826, 2022 Apr.
Article in English | MEDLINE | ID: mdl-32954869

ABSTRACT

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-ß-D-glucopyranosyl) atractyligenin (1) and 2-O-(2-O-isovaleryl-ß-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.


Subject(s)
Diterpenes, Kaurane , Xanthium , Diterpenes, Kaurane/chemistry , Fruit , Glucosides/chemistry , Glucosides/pharmacology , Humans , Xanthium/chemistry
13.
J Asian Nat Prod Res ; 24(1): 45-51, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33459052

ABSTRACT

Two new flavonoid glycosides named 6-hydroxy-3-methoxy-apigenin 7-O-α-ʟ-rhamnopyranoside (1) and 3-hydroxyl-apigenin 8-C-ß-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 IC50 values of 11.3 ± 1.7 and 8.9 ± 0.7 µM, respectively.


Subject(s)
Flavonoids , Glycosides , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Xanthium , Flavonoids/pharmacology , Glycosides/pharmacology , Molecular Structure , Phytochemicals/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Xanthium/chemistry
14.
J Asian Nat Prod Res ; 24(6): 518-527, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34212783

ABSTRACT

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.


Subject(s)
Diterpenes , Lignans , Xanthium , Animals , Fruit/chemistry , Glycosides/chemistry , Lignans/analysis , Lignans/pharmacology , Mice , Molecular Structure , Xanthium/chemistry
15.
Nat Prod Res ; 35(14): 2433-2437, 2021 Jul.
Article in English | MEDLINE | ID: mdl-31631691

ABSTRACT

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 IC50 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.


Subject(s)
Antineoplastic Agents/pharmacology , Biological Assay/methods , Phytochemicals/chemistry , Phytochemicals/pharmacology , Xanthium/chemistry , A549 Cells , Cell Death/drug effects , Furans/chemistry , Furans/pharmacology , Hep G2 Cells , Humans , Lactones/chemistry , Lactones/pharmacology , Plant Extracts/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology
16.
J Environ Sci Health B ; 56(1): 16-22, 2021.
Article in English | MEDLINE | ID: mdl-33048609

ABSTRACT

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%.


Subject(s)
Allelopathy , Herbicides/pharmacology , Plant Extracts/pharmacology , Weed Control/methods , Ambrosia/chemistry , Chenopodium album/drug effects , Cyclohexanones/pharmacology , Malvaceae/drug effects , Plant Weeds/drug effects , Water/chemistry , Xanthium/chemistry
17.
J Ethnopharmacol ; 258: 112914, 2020 Aug 10.
Article in English | MEDLINE | ID: mdl-32360046

ABSTRACT

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.


Subject(s)
Antidepressive Agents/pharmacology , Depression/drug therapy , Plant Extracts/pharmacology , Xanthium/chemistry , Animals , Antidepressive Agents/isolation & purification , Disease Models, Animal , Locomotion/drug effects , Male , Medicine, Traditional , Mice , Mice, Inbred BALB C , Plant Extracts/chemistry , Plant Leaves , Rats , Rats, Sprague-Dawley
18.
Bioorg Chem ; 97: 103696, 2020 04.
Article in English | MEDLINE | ID: mdl-32135360

ABSTRACT

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 (IC50 = 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 IC50 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 LC50 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.


Subject(s)
Botrytis/drug effects , Fungicides, Industrial/toxicity , Furans/toxicity , Plant Diseases/microbiology , Xanthium/chemistry , Amination , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Furans/chemical synthesis , Furans/chemistry , Models, Molecular , Plant Diseases/prevention & control , Sulfhydryl Compounds/chemical synthesis , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/toxicity
19.
Nat Prod Res ; 34(18): 2616-2620, 2020 Sep.
Article in English | MEDLINE | ID: mdl-30587055

ABSTRACT

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 G2/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, G2/M phase arrest, apoptosis and autophagosome accumulation. In summary, our findings demonstrated that Xanthatin caused G2/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.


Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Cell Cycle Checkpoints/drug effects , Colonic Neoplasms/drug therapy , Furans/therapeutic use , Signal Transduction/drug effects , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Asteraceae/chemistry , Cell Line, Tumor , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Furans/isolation & purification , Furans/pharmacology , G2 Phase Cell Cycle Checkpoints , Humans , Reactive Oxygen Species/metabolism , X-Linked Inhibitor of Apoptosis Protein/metabolism , Xanthium/chemistry
20.
Acta Pharmacol Sin ; 41(3): 404-414, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31700088

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Central Nervous System Neoplasms/drug therapy , Furans/pharmacology , Glioma/drug therapy , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Central Nervous System Neoplasms/metabolism , Central Nervous System Neoplasms/pathology , Dose-Response Relationship, Drug , Endoplasmic Reticulum Stress/drug effects , Furans/chemistry , Furans/isolation & purification , Glioma/metabolism , Glioma/pathology , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Rats , Structure-Activity Relationship , Tumor Cells, Cultured , Xanthium/chemistry
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