Euphorbia Pekinensis Research Articles

Toxic effects of Euphorbia pekinensis Rupr. and development of a validated UPLC/MS/MS method for profiling of urine metabolic changes

This paper was designed to study metabonomics characteristics of the hepatotoxicity and nephrotoxicity induced by JingDaJi (JDJ), a well-known traditional Chinese medicine which has been used for the treatment of scrofula, and as an antivirus and anti-inflammatory medication. Urinary samples from control and JDJ treated groups of rats were analyzed by ultra-performance liquid chromatography/mass spectrometry in positive ionization mode. Hepatic and renal tissues were histopathologically examined to identify specific changes occurring as a result of damage. The results suggested that the ethanol extract of JDJ (EJDJ) was responsible for the hepatotoxicity and nephrotoxicity that occurred following the ingestion of this medicinal herb. Using the principal components analysis, the levels of eight endogenous metabolites including creatinine, phenylacetylglycine, kynurenic acid, phenylalanine, leucine, hippuric acid, xanthurenic acid and 2,8-dihydroxyquinoline were found to be significantly changed in urine from EJDJ treated group. The formation of creatinine, phenylalanine, kynurenic acid, xanthurenic acid, leucine and 2,8-dihydroxyquinoline increased, while the biosynthesis of hippuric acid and phenylacetylglycine decreased.

Optimization of vinegar processing technique of Euphorbia pekinensis by multi-index orthogonal test

To optimize the vinegar processing technique of Euphorbia pekinensis. The test was designed by using orthogonal table L9 (3(4)). The factors were vinegar amount, proportion of vinegar and water and duration and degree of heating. An aggregative weighted method was used to optimize processing technology of E. pekinensis with content of euphol, extract of ethanol, extract of water and appearance and section were used as evaluative indicators. The optimal processing of E. pekinensis was identified as adding the mixture of 30 g vinegar and 270 g water to 100 g herbs, mixing evenly and softening, cooking until exhaustion under slow fire, taking out and drying to degree 6-7, and then cutting into thick slices. The study defines parameters of the processing technique of E. pekinensis. The quality of E. pekinensis is stable and controllable under the technical conditions.

Comparative study on toxicity of Euphorbia before and after being prepared by vinegar

To study and compare the changes of toxicity of Euphorbia pekinensis, E. kansui and E. ebracteolata before and after being prepared by vinegar. Small intestinal accentuation of mice and peritoneal macrophage NO release experiments were assessed to investigate the changes of toxicity of the three Chinese Medicines of Euphorbia before and after being prepared. E. pekinensis, E. kansui and E. ebracteolata and vinegar can obviously promot small intestinal accentuation and peritoneal macrophage NO release with the intensity of toxicity in the order of E. kansui > E. pekinensis > E. ebracteolata. After being prepared with vinegar, the toxicity of the three medicines decreased obviously compared to crude one. E. pekinensis, E. kansui and E. ebracteolata can induce inflammation and accelerate enterokinesis. After being prepared with vinegar, the irritation on Euphorbia decreased obviously.

Signaling Effects of Nitric Oxide, Salicylic Acid, and Reactive Oxygen Species on Isoeuphpekinensin Accumulation in Euphorbia pekinensis Suspension Cells Induced by an Endophytic Fungal Elicitor

Nitric oxide (NO), salicylic acid (SA), and reactive oxygen species (ROS) are important signal molecules that mediate plant resistance reactions and play important roles in secondary metabolism. To research the signal transduction pathway of the endophytic fungal elicitor from Fusarium sp. E5 promoting secondary metabolism in Euphorbia pekinensis suspension cells, the changes in NO, SA, ROS, and isoeuphpekinensin contents in the cells were investigated after elicitor addition to the cell suspension culture. The elicitor did not change H2O2 or O2− contents notably, whereas NO and SA contents were enhanced. Both the NO donator sodium nitroprusside (SNP) and SA enhanced isoeuphpekinensin content in the absence of the fungal elicitor, whereas the NO scavenger cPTIO and SA biosynthesis inhibitor cinnamic acid (CA) inhibited isoeuphpekinensin accumulation in the presence of the elicitor. In addition, cPTIO inhibited SA production induced by the fungal elicitor. CA did not inhibit NO production, but it significantly inhibited isoeuphpekinensin accumulation. The results demonstrated that in Euphorbia pekinensis suspension cells the endophytic fungal elicitor induced increased NO content and SA production, which promoted isoeuphpekinensin accumulation. ROS are clearly not involved in the endophytic fungus–host interaction signaling pathway.

First Report of Powdery Mildew on Euphorbia pekinensis Caused by Podosphaera euphorbiae-helioscopiae in China.

Euphorbia pekinensis Rupr, the Peking spurge, is a perennial grass that is planted throughout northeast China. Its roots can be used as a Chinese medicine for diuretic or purgative purposes. Some diterpenoids isolated from Euphorbia spp. show strong antitumor, antivirus, skin-irritating, and tumor-promoting activities. Some species contain chemicals that can be used as pesticides. In September and October 2009, spurge plants were seriously infected by powdery mildew fungi in Changchun Agri-Expon, Jilin Province, China. White mildew colonies appeared in early autumn and initial colonies coalesced to cover the entire upper sides of leaves, stems, and petals 3 to 4 weeks after the disease was noticed. Until late October, chasmothecia were observed on leaves and stems and the infected areas also became dark brown. Mycelium was amphigenous, in patches, white, and persistent. Conidia with distinct fibrosin bodies were ellipsoid-cylindrical, 21.6 to 33.8 × 12 to 15.6 μm, and produced in chains. Germ tubes arose near a pole of the conidia and terminated in simple, unlobed apices. Conidiophores were 59.8 to 139.9 μm; foot cells were straight to slightly flexuous, followed by one to three cells, and 24 to 48 × 8.4 to 10.8 μm. Hyphal appressoria were papillate. Chasmothecia were 70 to 95 μm in diameter, averaging 79.4 μm, and were immersed in mycelia. Mycelioid appendages (5 to 12) occurred in the lower part of the chasmothecia and were flexuous, curved, thick walled, and strongly undulate. Appendages were long (349-) 490 to 1,000 (-1,300) μm, averaging 759.4 μm. They were often densely crowded around the chasmothecia. Asci were single, sessile or short stalked, 60 to 80 × 45 to 70 μm, and eight spored. Ascospores were ellipsoid-ovoid and 16.8 to 28.8 × 10.8 to 18 μm. The fungus was identified as Podosphaera euphorbiae-helioscopiae on the basis of morphological characteristics of the anamorphic and teleomorphic stages. An herbarium specimen was deposited in the Herbarium of Mycology of Jilin Agriculture University (CJLCC100). Genomic DNA was extracted from the chasmothecia, and the internal transcribed spacer region (ITS) and the D1/D2 domains of the 28S rDNA were amplified and sequenced (GenBank Nos. JF795490 and JF795491). The ITS sequence has 98% identity with those of Podosphaera lini, P. macularis, and P. spiraeae, and the D1-D2 sequence of 28S rDNA has 99% identity with those of P. negeri and P. spiraeae, which indicated that this fungus belongs to the genus Podosphaera, even though there is no direct sequence evidence that it is P. euphorbiae-helioscopiae. P. euphorbiae-helioscopiae has only been previously reported in Japan (2), occurring on Euphorbia helioscopia. This species is unique because of the long and curved, thick-walled appendages, and there is no comparable species (1). P. euphorbiae-hirtae and P. euphorbiae are reported to infect Euphorbiaceae plants. Both species differ from P. euphorbiae-helioscopiae in their conspicuously shorter appendages (1,3). To our knowledge, this is the first reported occurrence of powdery mildew on E. pekinensis, and P. euphorbiae-helioscopiae is new to China. This is also the first description of the anamorph of the fungus since there is no record in the Erysiphales Database.

Effects of endophytic fungal elicitor on two kinds of terpenoids production and physiological indexes in Euphorbia pekinensis suspension cells

Treating Euphorbia pekinensis suspension cultures with endophytic fungal elicitor fromFusarium sp. E5 resulted in accumualtion of isoeuphpekinensin and euphol, activated defense-related enzymes, and increased biomass. The elicitor was prepared from extract of fungal endophyte Fusarium sp. E5 mycelium, and added into 21 day-old cell suspension cultures. The results showed that the biomass of culture after elicitor treatment was increased by 19.35%, whereas the isoeuphpekinensin and euphol contents were 5.81 and 3.56 times greater than those of the control, respectively. The activity of 1-deoxy-D-xylulose 5-phosphate synthase (a key enzyme of isoeuphpekinensin biosynthesis) was not increased significantly, while the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (a key enzyme of euphol) was increased by 1.67-fold compared with the control.Furthermore, the elicitor enhanced intracellular and extracellular polyphenol production and the activities of phenylalanine ammonia-lyase, peroxidase and catalase, therefore improved the plant defense ability. In addition, the nuclei of elicitor-treated cells were not apoptotic, and the culture was consistently healthy with increasing biomass. Our results demonstrate that endophytic fungal elicitor promotes both terpenoid biosynthesis and biomass of plant cultures for the first time, and thereby the information from this study will be helpful for large-scale medicinal plant suspension culture. Key words: Euphorbia pekinensis, endophytic fungal elicitor, terpenoids, Fusarium.

Two new casbane diterpenoids from the roots of Euphorbia pekinensis

From the roots of Euphorbia pekinensis, two new casbane diterpenoids, named pekinenins A (1) and B (2), were isolated. Their structures were elucidated as 18-hydroxy-1βH,2αH-casba-3E,7E,11E-trien-5-one (1), 5α-methoxy-1βH,2αH-casba-3Z,7E,11E-trien-18-oic acid (2) by a combination of 1D and 2D NMR spectroscopy and mass spectrometry. In the cytotoxicity assay of the two new compounds against Hela, MCF-7, and C6 human cancer cell lines, compound 1 showed moderate cytotoxic activity against two human cancer cell lines, Hela and C6, with IC50 values of 42.97 and 50.00 μM, respectively.

Molecular characterization and expression analysis of a gene encoding for farnesyl diphosphate synthase from Euphorbia pekinensis Rupr

The root of Euphorbia pekinensis as a traditional herbal medicine has been recorded in Chinese pharmacopoeias for the treatment of oedema, gonorrhea, migraine and wart cures. In this work, we reported on the cDNA cloning and characterization of a novel farnesyl diphosphate synthase (FPS) from E. pekinensis. The full-length cDNA named EpFPS (Genbank Accession Number FJ755465) contained 1431 bp with an open reading frame of 1029 bp encoding a polypeptie of 342 amino acids. The deduced amino acid sequence of the EpFPS named EpFPS exhibited a high homology with other plant FPSs, and contained five conserved domains. Phylogenetic analysis showed that EpFPS belonged to the plant FPS group. Southern blot analysis revealed that there exists a small FPS gene family in E. pekinensis. Expression pattern analysis revealed that EpFPS expressed strongly in root, weak in leaf and stem. In callus, expression of EpFPS gene and biosynthesis of triterpenoids were strongly induced by Methyl jasmonate and slightly induced by Salicylic acid. Functional complementation of EpFPS in an ergosterol auxotrophic yeast strain indicated that the cloned cDNA encoded a functional farnesyl diphosphate synthase.

A new cytotoxic casbane diterpene from Euphorbia pekinensis

A new cytotoxic casbane diterpene, named pekinenal, was isolated from the roots of Euphorbia pekinensis. Its structure was elucidated as 5alpha-hydroxy-1betaH,2alphaH-casba-3Z,7E,11E-triene-18-al by a combination of 1D- and 2D-NMR techniques and confirmed by X-ray crystallography. Pekinenal showed cytotoxic activity against all four human cancer cell lines tested.

Protective mechanism of KIOM-4 against streptozotocin induced diabetic cells: Involvement of heme oxygenase-1

KIOM-4 is a plant extract obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis. Previously, we reported that KIOM-4 protects pancreatic β-cells against streptozotocin (STZ) induced oxidative stress. To elucidate the cytoprotective mechanism of KIOM-4 on oxidative stress, we focused on the induction of heme oxygenase-1 (HO-1), which plays a role in cytoprotection against oxidative injury as well as providing an important function in the maintenance of homeostasis, in rat pancreatic β-cells (RINm5F). In this study, we showed that KIOM-4 up-regulated HO-1 expression at the mRNA and protein levels, thus resulting in increased HO-1 activity. HO-1 induction is regulated at the transcriptional level and is mediated by a specific enhancer, the antioxidant response element (ARE), which is found in the promoter of HO-1 gene. The transcription factor, NF-E2 related factor 2 (Nrf2), interacts with the ARE to activate HO-1 gene transcription and results in the modulation of HO-1 expression. KIOM-4 increased the nuclear translocation, ARE binding, and transcriptional activity of Nrf2. In addition, the extracellular regulated kinase (ERK) positively contributed to ARE-driven HO-1 expression. Furthermore, KIOM-4 elicited the activation of ERK and U0126 (inhibitor of ERK) attenuated the KIOM-4 induced activation of Nrf2, which subsequently decreased HO-1 protein levels. These findings suggest that the induction of HO-1 by KIOM-4 is dependent on the ERK pathway. Taken together, KIOM-4 enhances the cellular antioxidant defense system through the induction of HO-1 via the ERK-Nrf2-ARE signaling pathway, thereby protecting cells from streptozotocin-induced cell damage.

Intercropping peanut with traditional Chinese medicinal plants improves soil microcosm environment and peanut production in subtropical China

Many environmental issues affect peanut production in continuous monocropping system. Deterioration of soil microbial communities, especially for decrease in fungal diversity and increase in fungal pathogens, is widely hypothesized as a key factor for decreasing peanut production. In this study, a pot experiment was conducted to investigate the changes in soil microbial communities and peanut yield under the scheme of peanut intercropped with traditional Chinese medicinal plants, including Atractylodes lancea , Dioscorea zingiberebsis , Euphorbia pekinensis , Ophiopogon platyphyllum and Pinellia ternate . The results showed that soil microcosm environment was improved, and the fungal diversity and fungal pathogens such as Fusarium sp. and Verticillium sp. were restrained when peanut intercropped with A. lancea and E. pekinensis . The DGGE analysis of 18S-rRNA from DNA of the total soil communities showed obvious transferring of species of fungi between peanut monocropping and the intercropping systems. Compared with the control, the superoxide dismutase activity of peanut was increased by 43% in A. lancea and 37% in E. pekinensis intercropping systems, along with 37 and 16% yield improvement of peanut, respectively. Based on the result of the pot experiment, A. lancea and E. pekinensis were intercropped with peanuts in a field experiment. A considerable agreement was found between the results obtained from the field and pot experiments. Compared with peanut monocropping system, colony form unit of mould decreased by 31% in A. lancea and 18% in E. pekinensis intercropping treatments, where peanut yields were respectively increased by 39 and 35%. Further research should include integrated PCR-DGGE analysis to determine the transfer of peanut soil-born pathogens and its mechanism, and the optimization of intercropping system and planting density of medicinal plants to obtain the best benefits, and the understanding of the long-term effect of the intercropping systems.

Molecular cloning, characterization and function analysis of the gene encoding HMG-CoA reductase from Euphorbia Pekinensis Rupr

A new full-length cDNA encoding 3-hydroxy-3-methylglutoryl-Coenzyme A reductase (HMGR; EC1.1.1.34), which catalyzes the first committed step of isoprenoids biosynthesis in MVA pathway, was isolated from young leaves of Euphorbia Pekinensis Rupr. by rapid amplification of cDNA ends (RACE) for the first time. The full-length cDNA of HMGR (designated as EpHMGR, GenBank Accession NO. EF062569) was 2,200 bp containing a 1,752 bp ORF encoding 583 amino acids. Bioinformatic analyzes revealed that the deduced EpHMGR had extensive homology with other plant HMGRs and contained two transmembrane domains and a catalytic domain. The predicted 3-D model of EpHMGR had a typical spatial structure of HMGRs. Southern blot analysis indicated that at most two copies of EpHMGR gene existed in E. Pekinensis genome. Tissue expression analysis revealed that EpHMGR expressed strongly in roots, weakly in stems and leaves. The functional colour complementation assay indicated that EpHMGR could accelerate the biosynthesis of carotenoids in the Escherichia coli transformant, demonstrating that EpHMGR plays an influential role in isoprenoid biosynthesis.

Induction of Heme Oxygenase-1 by Plant Extract KIOM-79 via Akt Pathway and NF-E2 Related Factor 2 in Pancreatic β-Cells

The objective of the present study was to determine the mechanism by which KIOM-79 induced heme oxygenase-1 (HO-1) in rat pancreatic β-cells (RINm5F). A mixture of plant extracts (KIOM-79) was obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis. HO-1, an antioxidant phase 2 enzyme, was previously reported to possess cytoprotective properties in pancreatic β-cells. KIOM-79 induced heme oxygenase-1 (HO-1) expression at the mRNA and protein levels, leading to increased HO-1 activity. The transcription factor, NF-E2 related factor 2 (Nrf2), regulates the antioxidant response element (ARE) of the phase 2 detoxifying and antioxidant enzymes, resulting in modulation of HO-1 expression. KIOM-79 increased nuclear translocation, ARE binding, and transcriptional activity of Nrf2. Furthermore, KIOM-79 also elicited activation of Akt (protein kinase B) and LY294004 (inhibitor of Akt)-suppressed KIOM-79-induced activation of Nrf2, which subsequently decreased HO-1 protein levels. Taken together, these data suggest that KIOM-79 augments the cellular antioxidant defense capacity through induction of HO-1 via the Akt-Nrf2-ARE signaling pathway, thereby protecting cells from streptozotocin-induced oxidative stress.

보리 흰가루병 곰팡이 Fusarium graminearum에 대한 산초 추출물의 항진균 활성

The powdery mildew, a fungal plant disease found in varieties of plant cultures, is occurred by attack with Fusarium sp., Sphaerotheca sp., Leveilluna sp., and Eryshipe sp.. In this study we investigated the control of Fusarium graminearum, a barley powdery mildew fungus, by natural plant extracts. Among the 900 plant extracts tested, Zanthoxylum schinifolium, Ligusticum acutilobum, Bidens frondosa L., Dictamnus dasycarpus, Evodia officinalis, Disporum sessile, Scopolia japonica Max., Styrax japonica S. et Z., Dictamnus dasycarpus Turcz., Sinomenium acutum Rehder et Wils., Eugenia aromaticum, Rubus parvifolius L., Reynoutria elliptica, Coptis chinensis, Paeonia lactiflora Pall., Rheum undalatum, Paeonia suffruticosa, Oenothera odorata Jacq., Euphorbia pekinensis Rupr., and Nepeta cataria were selected based on spore germination inhibition assay. Further mycelial growth inhibition assay with economical and safety considerations led us to finally select Z. schinifolium (sancho) for control of F. graminearum. To produce antifungal sancho extract, methanol was suitable for extraction and subsequent fractionations of the extract showed that the water residue mainly had antifungal activity. The sancho extract and its fractions showed minor antibacterial activity against different pathogenic or food spoilage bacteria, but they did not show any harmful effects against young tomato plant by treatment of 1,000 ㎍/ml in green chamber test. These results suggested that the extract of sancho has high potentials on control of a powdery mildew fungus, F. graminearum.

Screening of endophytic fungi that promote the growth of Euphorbia pekinensis

This study explored a strategy to use endophytic fungi for promoting the growth of the medicinal plant, Euphorbia pekinensis. The growth of E. pekinensis was examined in pot culture following inoculation of E. pekinensis with endophytic fungal strains (Fusarium spp.) from E. pekinensis (E4 and E5) and those not from E. pekinensis (B3, B6 and S12). The results showed that plants treated with E4 or E5 exhibited significant increase in growth and all tested growth parameters, as compared to the control (CK). The biomass of E4- and E5-treated plants was 2.08 and 1.50 fold higher than that of CK. Analysis of superoxide dismutase (SOD) activity, the indicator of unsaturated fatty acids (IUFA), showed a similar trend as the growth biomass, indicating that the treatments of E4 and E5 benefited the growth of the host plantlets. Indole acetic acid (IAA) and gibberellin (GA) were found in the fermented broth of E4 and E5. E. pekinensis cell suspensions demonstrated similar responses to treatment with mycelia extract or filtrate of E5 culture medium. Replacement of MS culture medium components with E5 extracts in host cell suspensions suggested that E5 extract could replace auxin to enhance the plant growth. Therefore, strain E5 could be used as a growth-promoting strain for E. pekinensis. The method used in this study could be applicable to similar studies on the relationship between endophytic fungi and their host plants. This method provides a technique to accelerate the growth of E. pekinensis plantlets and suspension cells.

KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells

We evaluated whether KIOM-79, a mixture of extracts obtained from Puerariae lobata, Magnolia officinalis, Glycyrrhiza uralensis and Euphorbia pekinensis, could inhibit vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells cultured under high glucose (HG, 25 mM) or S100b (a specific ligand of the receptor for advance glycation end products (RAGE), 5 μg/ml). In this study, the effect of KIOM-79 on HG or S100b-induced VEGF expression was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, RT-PCR, ELISA, and Western blot on human RPE cells. The MTT assay ( p < 0.01) revealed that KIOM-79 (up to 1 mg/ml) had no effect on cell growth. HG or S100b induced an increase in expression of VEGF at both mRNA and protein levels ( p < 0.05; p < 0.01 versus control). The increase in VEGF expression by HG or S100b was dose- and time-dependently prevented by KIOM-79 ( p < 0.05 versus 25 mM glucose; p < 0.01 versus S100b). Also, KIOM-79 inhibited protein kinase C (PKC)-α/β α and p38 mitogen-activated protein kinase (MAPK) activation. Our results demonstrate that KIOM-79 can inhibit VEGF expression via inhibition of the MAPK and PKC pathway.

Cytoprotective Effects of KIOM-79 on Streptozotocin Induced Cell Damage by Inhibiting ERK and AP-1

The present study investigated the potential cytoprotective properties of a combination of plant extracts (KIOM-79) obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis, against the oxidative stresses induced by streptozotocin (STZ) in a rat pancreatic beta-cells (RINm5F). KIOM-79 was found to scavenge intracellular reactive oxygen species (ROS), thereby preventing DNA damage and lipid peroxidation. The KIOM-79 inhibited apoptosis of the beta-cells exposed to STZ via radical scavenging activity and activation of antioxidant enzymes. KIOM-79 inhibited activation of extracellular regulated kinase (ERK) induced by STZ and inhibited DNA binding activity of an activator protein-1 (AP-1), a downstream transcription factor of ERK. Taken together, these findings suggest that KIOM-79 protects against STZ induced cell death in RINm5F cells by inhibiting ROS generation and the ERK pathway.

Molecular Authentication of the Traditional Chinese Medicinal Plant Euphorbia pekinensis

The ITS regions of Euphorbia pekinensis and six other Euphorbia species used as adulterants of E. pekinensis were sequenced to differentiate them. The sequences are identical among the individuals in the seven species studies. Diversity in DNA sequences among various species was found ranging from 8.3% to 43.8% in ITS1 and 7.6% to 36.6% in ITS2 region. Furthermore, based on the divergent ITS regions, species-specific primers, JDJp 1 and JDJp 2, were designed in the polymorphic regions of E. pekinensis to distinguish it from adulterants. These ITS-derived primers amplified a 281-bp-specific DNA fragment from E. pekinensis. No amplified product was observed using DNA of six adulterants.

KIOM-79 inhibits LPS-induced iNOS gene expression by blocking NF-κB/Rel and p38 kinase activation in murine macrophages

We demonstrate that KIOM-79, combined extracts obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells. Treatment of RAW 264.7 cells with KIOM-79 inhibited LPS-stimulated nitric oxide production in a dose-related manner. Immunohisto-chemical staining of iNOS and RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Immunostaining of p65, EMSA, and reporter gene assay showed that KIOM-79 inhibited NF-κ/Rel nuclear translocation, DNA binding, and transcriptional activation, respectively. Western immunoblot analysis of p38 kinase showed KIOM-79 significantly inhibited the phosphoylation of p38 kinase which is important in the regulation of iNOS gene expression. Collectively, this series of experiments indicates that KIOM inhibits iNOS gene expression by blocking NF-κ/Rel and p38 kinase signaling. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of KIOM-79 on iNOS suggest that KIOM-79 may represent a useful anti-inflammatory agent.

Inhibitory activity for chitin synthase II from Saccharomyces cerevisiae by tannins and related compounds.

In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2"-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2"-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2"-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM. The inhibition appears to be selective for chitin synthase II, as they did not appreciably inhibit chitin synthase III.