Discovery and optimized extraction of the anti-osteoclastic agent epicatechin-7-O-ß-D-apiofuranoside from Ulmus macrocarpa Hance bark.

Ulmus macrocarpa Hance bark (UmHb) has been used as a traditional herbal medicine in East Asia for bone concern diseases for a long time. To find a suitable solvent, we, in this study, compared the efficacy of UmHb water extract and ethanol extract which can inhibit osteoclast differentiation. Compared with two ethanol extracts (70% and 100% respectively), hydrothermal extracts of UmHb more effectively inhibited receptor activators of nuclear factor κB ligand-induced osteoclast differentiation in murine bone marrow-derived macrophages. We identified for the first time that (2R,3R)-epicatechin-7-O-ß-D-apiofuranoside (E7A) is a specific active compound in UmHb hydrothermal extracts through using LC/MS, HPLC, and NMR techniques. In addition, we confirmed through TRAP assay, pit assay, and PCR assay that E7A is a key compound in inhibiting osteoclast differentiation. The optimized condition to obtain E7A-rich UmHb extract was 100 mL/g, 90 °C, pH 5, and 97 min. At this condition, the content of E7A was 26.05 ± 0.96 mg/g extract. Based on TRAP assay, pit assay, PCR, and western blot, the optimized extract of E7A-rich UmHb demonstrated a greater inhibition of osteoclast differentiation compared to unoptimized. These results suggest that E7A would be a good candidate for the prevention and treatment of osteoporosis-related diseases.

Ulmus davidiana 60% edible ethanolic extract for prevention of pericyte apoptosis in diabetic retinopathy.

Diabetic retinopathy (DR) is a disease that causes visual deficiency owing to vascular leakage or abnormal angiogenesis. Pericyte apoptosis is considered one of the main causes of vascular leakage in diabetic retina, but there are few known therapeutic agents that prevent it. Ulmus davidiana is a safe natural product that has been used in traditional medicine and is attracting attention as a potential treatment for various diseases, but its effect on pericyte loss or vascular leakage in DR is not known at all. In the present study, we investigated on the effects of 60% edible ethanolic extract of U. davidiana (U60E) and catechin 7-O-ß-D-apiofuranoside (C7A), a compound of U. davidiana, on pericyte survival and endothelial permeability. U60E and C7A prevented pericyte apoptosis by inhibiting the activation of p38 and JNK induced by increased glucose and tumor necrosis factor alpha (TNF-α) levels in diabetic retina. Moreover, U60E and C7A reduced endothelial permeability by preventing pericyte apoptosis in co-cultures of pericytes and endothelial cells. These results suggest that U60E and C7A could be a potential therapeutic agent for reducing vascular leakage by preventing pericyte apoptosis in DR.

Polyphase taxonomy and genome analysis reveal the adaptability of Luteolibacter rhizosphaerae sp. nov. to the rhizosphere soil of Ulmus pumila L.

A Gram-stain-negative, rod-shaped, non-flagellated, pale-yellow bacterium, designated GHJ8T, was isolated from the rhizosphere soil of Ulmus pumila L., Shanxi Province, China. Growth occurred at 20-37 °C (optimum, 28 °C), pH 6.0-11.0 (optimum, pH 8.0), and 0-1% NaCl (optimum, 0%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain GHJ8T was related to members of the genus Luteolibacter, and close to Luteolibacter flavescens GKXT (98.5%), Luteolibacter luteus G-1-1-1T (97.3%), Luteolibacter arcticus MC 3726T (97.2%), and Luteolibacter marinus NBU1238T (96.0%). The genome size of strain GHJ8T was 6.2 Mbp, with a G + C content of 62.5%. Genomic mining revealed that the strain contained antibiotic resistance genes and secondary metabolic gene clusters, indicating that it had adaptation mechanisms to environmental stress. Comparative genomic analyses clearly separated strain GHJ8T from the recognized species of the genus Luteolibacter based on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values below the thresholds for species delineation. The major cellular fatty acids were iso-C14:0 (30.8%), C16:1 ω9c (23.0%), C16:0 (17.3%), and C14:0 (13.4%). The quinone system was composed of the major menaquinones MK-8, MK-9, and MK-10, and the principal polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminophospholipid, an unidentified glycolipid, two unidentified phospholipids, and three unidentified lipids. Based on its phenotypic and genotypic properties and phylogenetic inference, strain GHJ8T is a novel species of the genus Luteolibacter, for which the name Luteolibacter rhizosphaerae sp. nov. is proposed. The type strain is GHJ8T (= GDMCC 1.2160T = KCTC 82452T = JCM 34400T).

Comparison analysis of metabolite profiling in seeds and bark of Ulmus parvifolia, a Chinese medicine species.

Ulmus parvifolia (U. parvifolia) is a Chinese medicine plant whose bark and leaves are used in the treatment of some diseases such as inflammation, diarrhea and fever. However, metabolic signatures of seeds have not been studied. The seeds and bark of U. parvifolia collected at the seed ripening stage were used for metabolite profiling analysis through the untargeted metabolomics approach. A total of 2,578 and 2,207 metabolites, while 503 and 132 unique metabolites were identified in seeds and bark, respectively. Additionally, 574 differential metabolites (DEMs) were detected in the two different organs of U. parvifolia, which were grouped into 52 classes. Most kinds of metabolites classed into prenol lipids class. The relative content of flavonoids class was the highest. DEMs contained some bioactive compounds (e.g., flavonoids, terpene glycosides, triterpenoids, sesquiterpenoids) with antioxidant, anti-inflammatory, and anti-cancer activities. Most kinds of flavonoids and sesquiterpenes were up-regulated in seeds. There were more varieties of terpene glycosides and triterpenoids showing up-regulated in bark. The pathway enrichment was performed, while flavonoid biosynthesis, flavone and flavonol biosynthesis were worthy of attention. This study identified DEMs with pharmaceutical value between seeds and bark during seed maturation and offered a molecular basis for alternative or complementary use of seeds and bark of U. parvifolia as a Chinese medicinal material.

Condensed tannins from Ulmus pumila L. leaves induce G2/M phase arrest and apoptosis via caspase-cascade activation in TFK-1 cholangiocarcinoma cells.

Condensed tannins the polyphenolic compounds that are widespread in plants have been proved to have antitumor potential. Here, we purified the bioactive condensed tannins from leaves of Ulmus pumila L. and explored their structural characteristics, antitumor effect on TFK-1 cholangiocarcinoma cells as well as the related potential mechanism. The UV-Vis, FT-IR spectroscopy, ESI-Full-MS, and thiolysis-HPLC-ESI-MS demonstrated that U. pumila condensed tannins (UCTs) consisted essentially of procyanidins with epicatechin as the main flavan-3-ol extension unit. The UCTs could significantly reduce the survival rate of human cholangiocarcinoma TFK-1, SK-CHA-1, and MZ-CHA-1 cells with the better inhibitory effect on TFK-1 cell proliferation. Flow cytometric assay showed that UCTs affected TFK-1 survival by G2/M phase arrest and inducing apoptosis in a dose-dependent manner. In addition, a total of 6592 differentially expressed genes (DEGs), consisting of 94 upregulated and 6498 downregulated DEGs, were identified between untreated and UCTs-treated TFK-1 cells using RNA-seq technology. Enrichment analysis based on the KEGG database revealed that these DEGs were closely associated with cell cycle and p53 apoptotic signaling pathways. Furthermore, qRT-PCR confirmed that treatment of UCTs to TFK-1 cells caused significant changes in the expression of cyclin E, cdc25 A, cytochrome c, caspase-3, and caspase-8. These results indicated that UCTs exhibited the growth inhibition effect on TFK-1 cells possibly via G2/M cell cycle arrest and activation of caspase-cascade to induce apoptosis, and had potential as an anti-cholangiocarcinoma drug for further development. PRACTICAL APPLICATIONS: Ulmus pumila L. as a valuable tree species has been widely used in fields of medicine and food. Condensed tannins, the polyphenolic compounds widespread in plants, have been proved to have antitumor potential and be safe to normal cells. In this study, the condensed tannins from leaves of U. pumila (UCTs) remarkably suppressed cholangiocarcinoma (CCA) cell viability possibly via G2/M cell cycle arrest and activation of caspase-cascade to induce apoptosis. The results provided evidence for the application of UCTs as a potential therapeutic drug for CCA tumor.

Does leaf gas exchange correlate with petiole xylem structural traits in Ulmus laevis seedlings under well-watered and drought stress conditions?

Several studies have shown that petiole xylem structure could be an important predictor of leaf gas exchange capacity, but the question of how petiole xylem structure relates to leaf gas exchange under different environment conditions remains unresolved. Moreover, knowledge of the amount of leaf gas exchange and structural variation that exists within a single species is also limited. In this study, we investigated the intraspecies coordination of leaf gas exchange and petiole xylem traits in 2-year-old seedlings of Ulmus laevis Pall. under well-watered and drought conditions. It was found that all studied petiole xylem traits of the elm seedlings were positively correlated with each other. This shows that the development of petiole xylem structure is internally well-coordinated. Nevertheless, the lower correlation coefficients between some petiole xylem traits indicate that the coordination is also individually driven. Drought stress reduced all studied leaf gas exchange traits and significantly increased intraspecies variation. In addition, drought stress also shifted the relationships between physiological traits and exhibited more structure-function relationships. This indicates the importance of petiole xylem structure in dictating water loss during drought stress and could partly explain the inconsistencies between leaf structure-function relationships studied under optimal conditions. Although several structure-function traits were related, the wide ranges of correlation coefficients indicate that the internal coordination of these traits substantially differs between individual elm seedlings. These findings are very important in the context of expected climatic change, as some degree of intraspecies variation in structure-function relationships could ensure the survival of some individuals under different environmental conditions.

No priming, just fighting-endophytic yeast attenuates the defense response and the stress induced by Dutch elm disease in Ulmus minor Mill.

One century after the first report of Dutch elm disease (DED), there is still no practical solution for this problem threatening European and American elms (Ulmus spp.). The long breeding cycles needed to select resistant genotypes and the lack of efficient treatments keep disease incidence at high levels. In this work, the expression of defense-related genes to the causal agent of DED, Ophiostoma novo-ulmi Brasier, was analyzed in in vitro clonal plantlets from two DED-resistant and two DED-susceptible Ulmus minor Mill. trees. In addition, the effect of the inoculation of an endophytic pink-pigmented yeast (Cystobasidium sp.) on the plant's defense system was tested both individually and in combination with O. novo-ulmi. The multifactorial nature of the resistance to DED was confirmed, as no common molecular response was found in the two resistant genotypes. However, the in vitro experimental system allowed discrimination of the susceptible from the resistant genotypes, showing higher levels of oxidative damage and phenolic compounds in the susceptible genotypes after pathogen inoculation. Inoculation of the endophyte before O. novo-ulmi attenuated the plant molecular response induced by the pathogen and moderated oxidative stress levels. Niche competition, endophyte-pathogen antagonism and molecular crosstalk between the host and the endophyte are discussed as possible mechanisms of stress reduction. In sum, our results confirm the complex and heterogeneous nature of DED resistance mechanisms and highlight the possibility of using certain endophytic yeasts as biological tools to improve tree resilience against biotic stress.

Anti-Obesity and Lipid Metabolism Effects of Ulmus davidiana var. japonica in Mice Fed a High-Fat Diet.

The root bark of Ulmus davidiana var. japonica (Japanese elm) is used in Korea and other East Asian countries as a traditional herbal remedy to treat a variety of inflammatory diseases and ailments such as edema, gastric cancer and mastitis. For this study, we investigated the lipid metabolism and anti-obesity efficacy of ethyl alcohol extract of Ulmus davidiana var. japonica root bark (UDE). First, HPLC was performed to quantify the level of (+)-catechin, the active ingredient of UDE. In the following experiments, cultured 3T3-L1 pre-adipocytes and high-fat diet (HFD)-fed murine model were studied for anti-obesity efficacy by testing the lipid metabolism effects of UDE and (+)-catechin. In the test using 3T3-L1 pre-adipocytes, treatment with UDE inhibited adipocyte differentiation and significantly reduced the production of adipogenic genes and transcription factors PPARγ, C/EBPα and SREBP-1c. HFD-fed, obese mice were administered with UDE (200 mg/kg per day) and (+)-catechin (30 mg/kg per day) by oral gavage for 4 weeks. Weight gain, epididymal and abdominal adipose tissue mass were significantly reduced, and a change in adipocyte size was observed in the UDE and (+)-catechin treatment groups compared to the untreated control group (***p < 0.001). Significantly lower total cholesterol and triglyceride levels were detected in UDE-treated HFD mice compared to the control, revealing the efficacy of UDE. In addition, it was found that lipid accumulation in hepatocytes was also significantly reduced after administration of UDE. These results suggest that UDE has significant anti-obesity and lipid metabolism effects through inhibition of adipocyte differentiation and adipogenesis.

Bakuchiol, main component of root bark of Ulmus davidiana var. japonica, inhibits TGF-ß-induced in vitro EMT and in vivo metastasis.

Cancer is a second leading cause of death worldwide, and metastasis is the major cause of cancer-related mortality. The epithelial-mesenchymal transition (EMT), known as phenotypic change from epithelial cells to mesenchymal cells, is a crucial biological process during development. However, inappropriate activation of EMT contributes to tumor progression and promoting metastasis; therefore, inhibiting EMT is considered a promising strategy for developing drugs that can treat or prevent cancer. In the present study, we investigated the anti-cancer effect of bakuchiol (BC), a main component of Ulmus davidiana var. japonica, in human cancer cells using A549, HT29 and MCF7 cells. In MTT and colony forming assay, BC exerted cytotoxicity activity against cancer cells and inhibited proliferation of these cells. Anti-metastatic effects by BC were further confirmed by observing decreased migration and invasion in TGF-ß-induced cancer cells after BC treatment. Furthermore, BC treatment resulted in increase of E-cadherin expression and decrease of Snail level in Western blotting and immunofluorescence analysis, supporting its anti-metastatic activity. In addition, BC inhibited lung metastasis of tail vein injected human cancer cells in animal model. These findings suggest that BC inhibits migration and invasion of cancers by suppressing EMT and in vivo metastasis, thereby may be a potential therapeutic agent for treating cancers.

Stem endophytes increase root development, photosynthesis, and survival of elm plantlets (Ulmus minor Mill.).

Long-lived trees benefit from fungal symbiotic interactions in the adaptation to constantly changing environments. Previous studies revealed a core fungal endobiome in Ulmus minor which has been suggested to play a critical role in plant functioning. Here, we hypothesized that these core endophytes are involved in abiotic stress tolerance. To test this hypothesis, two core endophytes (Cystobasidiales and Chaetothyriales) were inoculated into in vitro U. minor plantlets, which were further subjected to drought. Given that elm genotypes resistant to Dutch elm disease (DED) tend to show higher abiotic stress tolerance than susceptible ones, we tested the endophyte effect on two DED-resistant and two DED-susceptible genotypes. Drought stress was moderate; endophyte presence attenuated stomata closure in response to drought in one genotype but this stress did not affect plant survival. In comparison, long-term in-vitro culture proved stressful to mock-inoculated plants, especially in DED-susceptible genotypes. Interestingly, no endophyte-inoculated plant died during the experiment, as compared to high mortality in mock-inoculated plants. In surviving plants, endophyte presence stimulated root and shoot growth, photosynthetic rates, antioxidant activity and molecular changes involving auxin-signaling. These changes and the observed endophyte stability in elm tissues throughout the experiment suggest endophytes are potential tools to improve survival and stress tolerance of DED-resistant elms in elm restoration programs.

A 60% Edible Ethanolic Extract of Ulmus davidiana Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis.

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.

Arabidopsis, tobacco, nightshade and elm take insect eggs as herbivore alarm and show similar transcriptomic alarm responses.

Plants respond to insect eggs with transcriptional changes, resulting in enhanced defence against hatching larvae. However, it is unknown whether phylogenetically distant plant species show conserved transcriptomic responses to insect eggs and subsequent larval feeding. We used Generally Applicable Gene set Enrichment (GAGE) on gene ontology terms to answer this question and analysed transcriptome data from Arabidopsis thaliana, wild tobacco (Nicotiana attenuata), bittersweet nightshade (Solanum dulcamara) and elm trees (Ulmus minor) infested by different insect species. The different plant-insect species combinations showed considerable overlap in their transcriptomic responses to both eggs and larval feeding. Within these conformable responses across the plant-insect combinations, the responses to eggs and feeding were largely analogous, and about one-fifth of these analogous responses were further enhanced when egg deposition preceded larval feeding. This conserved transcriptomic response to eggs and larval feeding comprised gene sets related to several phytohormones and to the phenylpropanoid biosynthesis pathway, of which specific branches were activated in different plant-insect combinations. Since insect eggs and larval feeding activate conserved sets of biological processes in different plant species, we conclude that plants with different lifestyles share common transcriptomic alarm responses to insect eggs, which likely enhance their defence against hatching larvae.

Inhibitory Effects of AF-343, a Mixture of Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on Compound 48/80-Mediated Allergic Responses in RBL-2H3 Cells.

The purpose of this study was to determine the antiallergic effects of AF-343, a mixture of natural plant extracts from Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on rat basophilic leukemia (RBL-2H3) cells. The inhibitory effects on cell degranulation, proinflammatory cytokine secretion, and reactive oxygen species (ROS) production were studied in compound 48/80-treated RBL-2H3 cells. The bioactive compounds in AF-343 were also identified by HPLC-UV. AF-343 was found to effectively suppress compound 48/80-induced b-hexosaminidase release, and interleukin (IL)-4 and tumor necrosis factor-a (TNF-a) production in RBL-2H3 cells. In addition, AF-343 exhibited DPPH free radical scavenging effects in vitro (half-maximal inhibitory concentration (IC50) = 105 µg/mL) and potently inhibited compound 48/80-induced cellular ROS generation in a 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay. Specifically, treatment with AF-343 exerted stronger antioxidant effects in vitro and antiallergic effects in cells than treatment with three single natural plant extracts. Furthermore, AF-343 was observed to contain bioactive compounds, including catechin, aurantio-obtusin, and chicoric acid, which have been reported to elicit antiallergic responses. This study reveals that AF-343 attenuates allergic responses via suppression of b-hexosaminidase release, IL-4 and TNF-a secretion, and ROS generation, perhaps through mechanisms related to catechin, aurantio-obtusin, and chicoric acid. The results indicate that AF-343 can be considered a treatment for various allergic diseases.

Oral administration of Ulmus davidiana extract suppresses interleukin-1ß expression in LPS-induced immune responses and lung injury.

BACKGROUND: Ulmus davidiana (UD) is a traditional Korean herb medicine that is used to treat inflammatory disorders. UD has been shown to modulate a number of inflammatory processes in vitro or in vivo studies. However, the molecular mechanisms of UD on lipopolysaccharide (LPS)-induced acute lung injury remain to be understood. OBJECTIVE: The primary objective of this study is to determine the effect of UD bark water extract on LPS-induced immune responses and lung injury using both in vitro and in vivo models. METHODS: RAW 264.7 cells and a rat model of acute lung injury (ALI) were used to study the effects of UD on several parameters. Nitrite level, lactate dehydrogenase (LDH) level, and superoxide dismutase (SOD) activities were measured. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and plasma transaminase activities in blood were also determined. Pathological investigations were also performed. RESULTS: LPS infusion resulted in elevated IL-1ß mRNA expression, nitrite levels, TNF-α expression, and IL-1ß expression in RAW 264.7 cells. LPS infusion also increased levels of nitrite/nitrate, total protein, LDH, and TNF-α in bronchoalveolar lavage fluid, but reduced SOD levels in ex vivo and in vivo models. UD administration ameliorated all these inflammatory markers. In particular, treatment with UD reduced LPS-induced nitrite production in RAW 264.7 cells in a dose-dependent manner. UD treatment also counteracted the LPS-induced increase in alanine aminotransferase (ALT) and aspartate transaminase (AST) activity in rat plasma, leading to a significant reduction in ALT and AST activity. CONCLUSIONS: The results revealed that UD treatment reduces LPS-induced nitrite production, IL-1ß mRNA expression, and TNF-α expression. In addition, LPS-induced decrease in SOD level is significantly elevated by UD administration. These results indicate that UD extract merits consideration as a potential drug for treating and/or preventing ALI.

Hepatoprotective and neuroprotective flavanes from the fruits of Ulmus pumila L. (Ulmaceae).

Phytochemical study of the EtOAc fraction (active extract) of the fruits of Ulmus pumila L. resulted in the isolation of thirteen flavane derivatives, and they were identified by their precise spectral data and literature. All the compounds (1-13) were obtained from the fruits of U. pumila L. for the first time. Meanwhile, the compounds (1-13) were assayed for their hepatoprotective and neuroprotective activities, respectively. Compounds 1, 2, 5, 7 and 8 (10µM) exhibited remarkable hepatoprotective activities, and compounds 9, 10, and 13 showed significant neuroprotective activities with IC50 values of 4.08, 5.34, and 2.02µM, respectively.

Study on the differential gene expression of elm leaves fed on by Tetraneura akinire Sasaki.

BACKGROUND: To study the essential molecular mechanism of gall formation is very important. OBJECTIVE: To investigate the differential gene expression in leaves fed on by Tetraneura akinire Sasaki and to provide a basis for the better understanding of the essential molecular mechanism of gall formation. METHODS: The infected leaves of the elm were divided into three periods: initial formation period (T2), growth and differentiation period (T3), and cracking period (T4). The untouched leaves were used as the control (T1). RNA-Seq was performed, and the high-quality sequences were mapped to the reference genome and the elm gene database to obtain the gene expression profiles. The expression level of each gene was calculated by the RPKM method. A combination of FDR ≤ 0.01 and the absolute value of |log2 ratio (T/CK)| ≥ 2 was used as the threshold to determine the significance of gene expression. Finally, GO and pathway enrichment analyses were used to identify the significantly enriched functional classification and metabolic pathways in DEGs. RESULTS: The results revealed that approximately 244 mRNAs were detected between T1 and T2, including 192 up-regulated and 52 down-regulated mRNAs; approximately 175 mRNAs were detected between T1 and T3, including 145 up-regulated and 30 down-regulated mRNAs; and approximately 372 mRNAs were detected between T1 and T4, including 360 up-regulated and 12 down-regulated mRNAs. Approximately 34 differentially expressed genes were identified by Venn analysis. Comparing the three infection periods to the control, there were 28 up-regulated and six down-regulated mRNAs. Additionally, 562 genes were used for cluster analysis, which revealed that the gene expression in T2 and T3 changed greatly. Genes related to cell proliferation and respiration, such as microtubulin and 6-phosphoric acid fructose kinase were mainly up-regulated during the T2 period. Genes encoding lipoxygenase, glutathione-S-transferase, superoxide dismutase and protease inhibitor were up-regulated during T2 and T3. Genes encoding lignocellulose synthase were up-regulated during T4, which suggests the reinforcement of the cell wall to improve the resistance to the damage of the Tetraneura akinire Sasaki. CONCLUSIONS: The results showed that the feeding of Tetraneura akinire Sasaki caused the differential expression of elm genes and influenced cellular energy metabolism. These changes in physiological response and gene expression of the elm compose the physiological and molecular basis of the gall formation and may improve the resistance of elm to Tetraneura akinire Sasaki.

Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. METHODS: Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. RESULTS: UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. CONCLUSION: UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.

Identification of flavonoids and chlorogenic acids in elm fruits from the genus Ulmus and their antioxidant activity.

Elm fruits were once an important food source in the years of famine. Research on the functional compounds in elm fruits was almost unavailable. In this study, we established an efficient high-performance liquid chromatography method for the simultaneous separation of eight chlorogenic acids and 28 flavonoids in elm fruits for the first time. Total flavonoid contents ranged from 286 mg/100 g (Ulmus laciniata) to 1228 mg/100 g (U. pumila). High concentrations of rutin, quercetin 3-O-glucoside, and kaempferol derivatives were present in U. laevis, U. castaneifolia, and U. pumila, respectively. Furthermore, the fruit extracts of U. americana, U. castaneifolia, U. davidiana, and U. pumila showed higher antioxidant activity. These results suggest that fruits of these species can be used as bioresources for the extraction of the corresponding functional compounds. This work provides informative data and can be an important reference for future research on elm fruits as a renewed food resource.

Chemical constituents of the root bark of Ulmus davidiana var. japonica and their potential biological activities.

The root bark of Ulmus davidiana var. japonica (Ulmaceae), commonly known as yugeunpi, has been used as a traditional Korean medicine for the treatment of gastroenteric and inflammatory disorders. As part of continuing projects to discover bioactive natural products from traditional medicinal plants with pharmacological potential, phytochemical investigation of the root bark of this plant was carried out. This led to the successful isolation of a new chromane derivative (1) and 22 known compounds: catechin derivatives (2-5), megastigmane glycoside (6), dihydrochalcone glycosides (7 and 8), flavanone glycosides (9 and 10), coumarins (11 and 12), lignan derivatives (13-17), and phenolic compounds (18-23). The structure of the new compound (1) was determined with 1D and 2D NMR spectroscopy and HR-ESIMS, and its absolute configurations were achieved by chemical reactions and the gauge-including atomic orbital (GIAO) NMR chemical shifts calculations. All the isolated compounds were evaluated for their potential biological activities including neuro-protective, anti-neuroinflammatory, and anti-Helicobacter pylori activities. Among the isolates, compounds 1, 8, and 20 displayed stronger potency by causing a greater increase in the production and the activity of nerve growth factor (NGF) in C6 glioma cells (147.04 ±â€¯4.87, 206.27 ±â€¯6.70, and 143.70 ±â€¯0.88%, respectively), whereas compounds 11, 14, and 19 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine microglial cells (IC50 of 18.72, 12.31, and, 21.40 µM, respectively). In addition, compounds 1, 11, 18, and 20 showed anti-H. pylori activity with MIC values of 25 or 50 µM against two strains of H. pylori 51 and 43504. These findings provide scientific evidence that supports the traditional usage of U. davidiana var. japonica root bark in the treatment of gastroenteric and inflammatory disorders.

Ulmus macrocarpa Hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway.

Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.