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ObjectiveTo investigate the protective effect and mechanism of Euphorbia helioscopia aqueous extract （EHE） on mice with chronic obstructive pulmonary disease （COPD） and its influence on precancerous lesion-associated proteins in lung tissues induced by cigarette smoke （CS）. MethodThe COPD model was induced by CS in 60 mice and the model mice were randomly divided into control group， model group， positive drug group （dexamethasone， 2 mg·kg-1）， and low-， medium-， and high-dose EHE groups （1.875， 3.75， 7.5 g·kg-1）. The high-performance liquid chromatography （HPLC） method was used to determine the related components in EHE. The changes in end-expiratory pause （EEP）， airway resistance （Penh）， expiratory flow at 50% vital capacity （EF50）， and other pulmonary function indexes were detected by the spirometer. The levels of inflammatory factors， such as interleukin （IL）-2， IL-5， IL-18， IL-17A， and IL-27 in bronchoalveolar lavage fluid （BALF） of mice were detected by high-throughput liquid protein chip technology. Hematoxylin-eosin （HE） staining was used to detect the pathological changes in lung tissues in mice. The content of malondialdehyde （MDA）， myeloperoxidase （MPO）， and glutathione peroxidase （GSH-Px） in lung tissues was determined by the colorimetric method. The mRNA relative expression of tumor necrosis factor-α （TNF-α）， transforming growth factor-β （TGF-β）， matrix metalloproteinase-2 （MMP-2）， matrix metalloproteinase-9 （MMP-9）， and matrix metalloproteinase-12 （MMP-12） was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Immunohistochemistry （IHC） was used to detect the expression of tumor protein （P53） and cell proliferation-associated antigen （Ki67） in lung tissues， and Western blot was used to detect the relative expression of tumor suppressor protein （P16）， DNA （cytosine-5）-methyltransferase 1 （DNMT1）， and fragile histidine triad （FHIT） in lung tissues. ResultThe results showed that the main compounds in EHE included phenols （gallic acid and protocatechuic acid） and flavonoids （such as hyperoside， rutin， myricetin， naringenin， quercetin， luteolin， kaempferol， and licorice chalcone A）， among which gallic acid and rutin were the highest in content. Compared with normal group， model group showed increased levels of EEP， EF50， and Penh （P<0.05）， and showed increased MDA and MPO levels （P<0.01） and decreased GSH-Px （P<0.01）， and the model group displayed increased levels of IL-2， IL-5， IL-18， IL-17A， IL-27， TNF-α， TGF-β， MMP-2， MMP-9， and MMP-12 （P<0.05）. And the model group exhibited up-regulated expression of P53， Ki67， and FHIT in lung tissues （P<0.01） and down-regulated expression of DNMT1 and P16 （P<0.01）. Compared with model group， the EHE groups showed decreased EEP and EF50 levels （P<0.05）. The pathological injury of lung tissues in mice of the model group was observed under HE staining， and the pathological injury of basal cell hyperplasia of lung tissues was gradually improved after treatment with EHE. The EHE groups showed reduced levels of MDA and MPO （P<0.01） and increased GSH-Px （P<0.01）. The EHE groups displayed decreased levels of IL-2， IL-5， IL-18， IL-17A， IL-27， TNF-α， TGF-β， MMP-2， MMP-9， and MMP-12 （P<0.05）. And the EHE groups showed down-regulated Ki67 and FHIT in lung tissues （P<0.05） and up-regulated expression of P53 and DNMT1 （P<0.05）. ConclusionEHE can protect mice from COPD and inhibit precancerous lesions， and the mechanism may be related to the inhibition of inflammation and oxidative stress response， regulation of protease and antiprotease imbalance， and regulation of epithelial cell growth.
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ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia， and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease（COPD）. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C18 column（3 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase for gradient elution（0-15 min， 5%-30%B； 15-20 min， 30%-50%B； 20-30 min， 50%-95%B； 30-35 min， 95%-5%B）， and the detection wavelength of 190-800 nm， column temperature of 40 ℃， flow rate of 0.3 mL∙min-1 and injection volume of 4 μL. The electrospray ionization（ESI） was used in positive and negative ion modes， and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function， biological process， cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components. ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia， 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin， quercetin， apigenin， naringenin and helioscopinolide C were the key components of E. helioscopia against COPD， and vascular endothelial growth factor A（VEGFA）， albumin（ALB）， protein kinase B1（Akt1）， tumor necrosis factor（TNF） and interleukin-6（IL-6） were the key targets. Molecular docking results showed that one diterpene lactone（helioscopinolide C） and three flavonoids（naringenin， luteolin， apigenin） in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD. ConclusionNaringenin， helioscopinolide C， luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.
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Objective:To study the protective effect of Euphorbia helioscopia alcohol extract on lipopolysaccharide (LPS) -induced acute lung injury in mice and explore its possible mechanism. Method:The 50 Balb/c male mice were randomly divided into 5 groups, including normal group, model group, dexamethasone group (1.5 mg·kg-1), E. helioscopia alcohol extracts group (7.5，3.75 g·kg-1). Except for the normal group, the other groups used intranasal instillation of LPS to establish a model of acute lung injury in mice. The type and number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were detected by automatic blood analyzer and Wright-Giemsa composite staining. The lung tissue damage was observed by hematoxylin-eosin (HE) staining. The contents of the inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF were detected by flow cytometry. The protein expressions of nuclear factor kappa-B p65(NF-κB p65), phospho-NF-κB p65 (p-NF-κB p65), inhibitor of NF-κBα (IκBα), phospho-IκBα (p-IκBα) in NF-κB pathway and c-Jun N-terminal kinase (JNK), phospho-JNK (p-JNK), p38 protein (p38), phospho-p38 (p-p38), extracellular regulated protein kinases (ERK1/2), phospho-ERK1/2 (p-ERK1/2) in mitogen-activated protein kinase (MAPK) pathway were determined by Western blot. Result:Compared with normal control group, the lung tissue of the model group showed obvious damage, in which a large number of inflammatory cells infiltrated, and the integrity of the alveoli was destroyed. Inflammatory factors TNF-α, IL-6 in BALF and p-NF-κB p65, p-JNK, p-p38, p-ERK protein expression levels in lung tissue were significantly increased (P<0.01). Compared with model group, the pathological damage of lung tissue in mice with high dose of E. helioscopia alcohol extract and dexamethasone positive group was significantly alleviated. The levels of TNF-α and IL-6 in BALF and the expression levels of p-NF-κB p65, p-JNK, p-p38 and p-ERK1/2 protein in lung tissue were significantly down-regulated (P<0.01). Conclusion:The E. helioscopia alcohol extract has a protective effect on LPS-induced acute lung injury in mice, its mechanism may be related to the regulation of the NF-κB/MAPK signaling pathway.
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Objective: To investigate the chemical constituents from Euphorbia helioscopia. Methods: The compounds were isolated and purified using macroporous resin, silica gel colimu, ODS, MCI gel and Sephadex LH-20, and their structures were elucidated on the basis of spectral data and physicochemical properties. Results: Sixteen compounds were isolated from 95% ethyl alcohol extract from the whole arial of E. helioscopia and identified as four terpenoides: helioscopinolide E (1), ent-kaurane-3-oxo-16β-17-diol (2), oleanolic acid (3), betulinic acid (4); six phenolics: benzoic acid (5), ethyl gallate (6), 3, 3', 4, 4'-tetrahydroxy diphenyl (7), brevifolin (8), 6-hydroxy-7, 8-methylenedioxy coumarin (9), 3, 3'-di-O-methylellagic acid (10); and five phenolics: apigenin (11), chrysoeriol (12), hyperin (13), naringenin-7-O-β-D-glucoside (14), cannabisci-trin (15), and 3β-hydroxy-cholesta-5-ene (16). Conclusion: Compounds 7-10 and 12 are isolated from this genus for the first time. Compounds 2-5 and 14-15 are isolated from this plant for the first time.
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The EtOH extracts of the whole plants of afforded 17 new jatrophane diterpenoid esters, helioscopianoids A-Q (-), along with eight known compounds (-). Their structures were elucidated by extensive spectroscopic methods and Mo(OAc)-induced ECD analysis, and the structures of compounds , , and were confirmed by X-ray crystallography. Compounds - were evaluated for inhibitory effects on P-glycoprotein (P-gp) in an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR) and neuroprotective effects against serum deprivation-induced and rotenone-induced PC12 cell damage. Compounds and increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound could attenuate rotenone-induced PC12 cell damage, and compounds , , and showed neuroprotective activities against serum deprivation-induced PC12 cell damage.
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Objective To investigate the effect of Euphorbia helioscopia on MDA-MB-231 cells and its mechanism.Methods The cell viability was detected by MTT assay.The production of ROS in MDA-MB-231 cells was measured by fluorescence microscopy.The apoptotic rate was detected by flow cytometry.Apoptosis DNA fragments were detected by TUNEL assay.Western blot was used to assess the expression of caspase-9, caspase-3 and PARP.Results MTT assay showed that the extract significantly inhibited the viability of MDA-MB-231 cells, which can be diminished by the ROS inhibitor NAC and the caspase inhibitor Z-VAD-FMK.The marked increase in the production of ROS induced by the extract was observed with fluorescence microscopy.Flow cytometry showed that the PI positive staining cells increased significantly after the treatment of the extract, but was diminished by NAC.Caspase-9 and caspase-3 were activated after the treatment of the extract while the PARP was cleaved.TUNEL showed that a significant increase in apoptotic DNA fragmentation induced by the extract, which can be diminished by NAC and Z-VAD-FMK.Conclusion Ethyl acetate extract inhibited the MDA-MB-231 cells and induced apoptosis.The mechanism may involve with the mitochondrial damage due to the excessive ROS.
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The present study was designed to isolate and evaluate the antibacterial activity of the compounds from the whole plant of Euphorbia helioscopia L.. Various chromatographic techniques were used to isolate and purify the compound. The structure of the compound was elucidated on basis of spectral data ((1)H NMR, (13)C NMR, (1)H-(1)H COSY, HSQC, HMBC, NOESY, IR, and HR-ESI-MS). A new jatrophone-type diterpenoid (14α,15β-diacetoxy-3β-benzoyloxy-7β-nicotinoyloxy-9-oxo-jatropha-5E,11E-diene), named euphoheliosnoid E (1), was isolated from the whole plant of E. helioscopia L. Compound 1 showed significant anti-microbial activity against oral pathogens.
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Antiinfecciosos , Farmacología , Diterpenos , Química , Farmacología , Euphorbia , Química , Estructura Molecular , Enfermedades de la Boca , Microbiología , Niacina , Química , Farmacología , Extractos Vegetales , Química , FarmacologíaRESUMEN
Objective: To evaluate in vivo antioxidant activity of latex and leaves methanol extract of Euphorbia helioscopia using mice as experimental animals. Methods: The plant was collected, identified, dried under shade, ground to fine powder and extraction was done. Latex was collected in dried bottles by cutting the stem. Oxidative stress was induced in mice with acute toxic dose of paracetamol administered intrperitoneally. Latex and leaves methanol extract (600 and 1 200 mg/kg) orally, once a day, were given to mice for two weeks. Then oxidative stress biomarkers were measured in tissue homogenates and serum. Results: Leaves methanol extract exhibited prominent in vivo antioxidant effect as compared to latex. Results showed significant rise in antioxidant enzymes (catalase, superoxide dismutase and glutathione) levels at 1 200 mg/kg dose of extract. Thus, extract helped to detoxify the free radicles by increasing antioxidant enzymes levels. Malondialdehyde value decreased significantly with extract (1 200 mg/kg) which was indicator of extract's power to inhibit the generation of free radicals. Extract (1 200 mg/kg) exhibited maximum cure against stress induced changes in liver, kidney, lipid profile parameters and complete blood count. Conclusions: Leaves methanol extract of Euphorbia helioscopia raised antioxidant enzymes levels in mice. It showed hepatorenal-curative effect, hypolipidemic effect and hemostasis potential. Thus, it can help the biological systems to fight against stress induced pathological conditions.
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OBJECTIVE@#To evaluate in vivo antioxidant activity of latex and leaves methanol extract of Euphorbia helioscopia using mice as experimental animals.@*METHODS@#The plant was collected, identified, dried under shade, ground to fine powder and extraction was done. Latex was collected in dried bottles by cutting the stem. Oxidative stress was induced in mice with acute toxic dose of paracetamol administered intrperitoneally. Latex and leaves methanol extract (600 and 1 200 mg/kg) orally, once a day, were given to mice for two weeks. Then oxidative stress biomarkers were measured in tissue homogenates and serum.@*RESULTS@#Leaves methanol extract exhibited prominent in vivo antioxidant effect as compared to latex. Results showed significant rise in antioxidant enzymes (catalase, superoxide dismutase and glutathione) levels at 1 200 mg/kg dose of extract. Thus, extract helped to detoxify the free radicles by increasing antioxidant enzymes levels. Malondialdehyde value decreased significantly with extract (1 200 mg/kg) which was indicator of extract's power to inhibit the generation of free radicals. Extract (1 200 mg/kg) exhibited maximum cure against stress induced changes in liver, kidney, lipid profile parameters and complete blood count.@*CONCLUSIONS@#Leaves methanol extract of Euphorbia helioscopia raised antioxidant enzymes levels in mice. It showed hepatorenal-curative effect, hypolipidemic effect and hemostasis potential. Thus, it can help the biological systems to fight against stress induced pathological conditions.