Effect of fermentation on antioxidant, antimicrobial, anti-inflammatory, and anti-Helicobacter pylori adhesion activity of Ulmus davidiana var. japonica root bark.

The limited yield of Ulmus davidiana var. japonica root bark (URB) extract is considered an economic loss to the food industry. Improving extraction yield and bioactivity through fermentation increase the industrial usage of URB. The study aims to optimize the fermentation with cellulolytic and pectinolytic bacteria and evaluate the bioactivity and anti-Helicobacter pylori activity of the fermented URB extract. URB fermentation with the Bacillus licheniformis FLa3, isolated from salted seafood (Sardinella zunasi), under optimal conditions (37 °C, pH 6, 10% inoculum dose, and 36 h) improved the extraction yield by 36% compared to the control. The antioxidant and antimicrobial activity of the fermented extract were significantly higher than non-fermented extract. High-performance liquid chromatography results confirmed that the fermentation increased the proportion of bioactive components such as catechin (171.7%), epicatechin (144.3%), quercetin (27.3%), and kaempferol (16.7%). The results confirmed that the fermentation increased both the extraction yield and bioactivity.

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.

Ultrasonication, immune activity, and photocrosslinked microgel formation of pectic polysaccharide isolated from root bark of Ulmus davidiana var. japonica (Rehder) Nakai.

The root bark of Ulmus davidiana var. japonica (Rehder) Nakai (Japanese elm) has been used for inflammatory disease treatments. In this work, we isolated pectic polysaccharides from the root bark of U. davidiana (UDP) and explored the immune activities of intact and ultrasonicated UDP on human macrophages. The UDP-treated macrophages showed a proinflammatory response, indicating classical activation via Toll-like receptor-mediated recognition. For hydrogel formation, the ultrasonicated UDP was modified with methacrylate groups, then subjected to photocrosslinking. The formed bulk hydrogel was pulverized into microgels by homogenization, and the microgel size was modulated for macrophage phagocytosis. The UDP microgel-treated macrophages displayed microgel internalization and classical activation that involved upregulation of M1 polarization markers (IL6, TNF-α, and CCR7), indicating that the microgel can be used as a carrier for macrophage-targeted drug delivery.

Inhibitory Effect of Ulmus davidiana and Cornus officinalis Extracts on Osteoporotic Bone Loss In Vitro and In Vivo.

Background and Objectives: Traditional herbal medicines are becoming more popular as a complementary medication as they have the advantages of being mostly harmless and safe, causing fewer side-effects than conventional medications. Here, we demonstrate the inhibitory effects of the combination of Ulmus davidiana (UD) and Cornus officinalis (CO) extracts on osteoporotic bone loss. Materials and Methods: This study presented osteogenic effects in primary cultured osteoblasts, pre-osteoblastic MC3T3-E1 cell lines, and osteoclastogenic effects in osteoclasts derived from bone marrow monocytes, and finally, protective effects on bone loss in an ovariectomy (OVX)-induced osteoporotic animal model. Results: A significant increase in alkaline phosphatase (ALP) activity was observed following treatment with UD and CO mixtures (8:2, 7:3, and 5:5 ratios) and individual UD and CO extracts, with the highest ALP activity being detected for the treatment with UD and CO extracts at a 5:5 ratio. An optimal ratio of UD and CO (UC) extract promoted osteoblast differentiation in both pre-osteoblastic cells and primary osteoblasts by increasing osteoblastic markers such as Alpl, Runx2, and Bglap. However, treatment with the UC extract inhibited osteoclast differentiation with a decreased expression of osteoclastogenesis-related genes, including Ctsk, Acp5, Mmp9, and Nfatc1. In addition, UC treatment prevented osteoporotic bone loss in OVX mice and improved impaired skeletal structure parameters. Conclusions: This study suggests that combined UD and CO extracts may be a beneficial traditional medicine for the prevention of postmenopausal osteoporosis.

Scaling the leaf length-times-width equation to predict total leaf area of shoots.

BACKGROUND AND AIMS: An individual plant consists of different-sized shoots, each of which consists of different-sized leaves. To predict plant-level physiological responses from the responses of individual leaves, modelling this within-shoot leaf size variation is necessary. Within-plant leaf trait variation has been well investigated in canopy photosynthesis models but less so in plant allometry. Therefore, integration of these two different approaches is needed. METHODS: We focused on an established leaf-level relationship that the area of an individual leaf lamina is proportional to the product of its length and width. The geometric interpretation of this equation is that different-sized leaf laminas from a single species share the same basic form. Based on this shared basic form, we synthesized a new length-times-width equation predicting total shoot leaf area from the collective dimensions of leaves that comprise a shoot. Furthermore, we showed that several previously established empirical relationships, including the allometric relationships between total shoot leaf area, maximum individual leaf length within the shoot and total leaf number of the shoot, can be unified under the same geometric argument. We tested the model predictions using five species, all of which have simple leaves, selected from diverse taxa (Magnoliids, monocots and eudicots) and from different growth forms (trees, erect herbs and rosette herbs). KEY RESULTS: For all five species, the length-times-width equation explained within-species variation of total leaf area of a shoot with high accuracy (R2 > 0.994). These strong relationships existed despite leaf dimensions scaling very differently between species. We also found good support for all derived predictions from the model (R2 > 0.85). CONCLUSIONS: Our model can be incorporated to improve previous models of allometry that do not consider within-shoot size variation of individual leaves, providing a cross-scale linkage between individual leaf-size variation and shoot-size variation.

Regulation of Cytokines and Dihydrotestosterone Production in Human Hair Follicle Papilla Cells by Supercritical Extraction-Residues Extract of Ulmus davidiana.

This study was conducted to examine the anti-hair loss mechanism of the supercritical fluid extraction-residues extract of Ulmus davidiana by the regulation of cytokine production and hormone function in human dermal follicle papilla cells (HDFPCs). To investigate the modulatory effects on H2O2-induced cytokines, we measured transforming growth factor-beta and insulin-like growth factor 1 secreted from HDFPCs. To investigate the regulatory effects of supercritical extraction-residues extract of Ulmus davidiana on dihydrotestosterone hormone production, cells were co-incubated with high concentrations of testosterone. The supercritical extraction-residues extract of Ulmus davidiana significantly inhibited the secretion of transforming growth factor-beta but rescued insulin-like growth factor 1 in a dose-dependent manner. The supercritical extraction-residues extract of Ulmus davidiana markedly reduced dihydrotestosterone production. These results suggest that the supercritical fluid extract residues of Ulmus davidiana and their functional molecules are candidates for preventing human hair loss.

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.

Inhibition of soluble epoxide hydrolase by phytochemical constituents of the root bark of Ulmus davidiana var. japonica.

A novel compound 1 and nine known compounds (2-10) were isolated by open column chromatography analysis of the root bark of Ulmus davidiana. Pure compounds (1-10) were tested in vitro to determine the inhibitory activity of the catalytic reaction of soluble epoxide hydrolase (sEH). Compounds 1, 2, 4, 6-8, and 10 had IC50 values ranging from 11.4 ± 2.3 to 36.9 ± 2.6 µM. We used molecular docking to simulate inhibitor binding of each compound and estimated the binding pose of the catalytic site of sEH. From this analysis, the compound 2 was revealed to be a potential inhibitor of sEH in vitro and in silico. Additionally, molecular dynamics (MD) study was performed to find detailed interaction signals of inhibitor 2 with enzyme. Finally, compound 2 is promising candidates for the development of a new sEH inhibitor from natural plants.

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.

Ulmusakidian, a new coumarin glycoside and antifungal phenolic compounds from the root bark of Ulmus davidiana var. japonica.

Bioactivity-driven LC/MS-based phytochemical analysis of the root bark extract of Ulmus davidiana var. japonica led to the isolation of 10 compounds including a new coumarin glycoside derivative, ulmusakidian (1). The structure of the new compound was elucidated using extensive spectroscopic analyses via 1D and 2D NMR spectroscopic data interpretations, HR-ESIMS, and chemical transformation. The isolated compounds 1-10 were tested for their antifungal activity against human fungal pathogens Cryptococcus neoformans and Candida albicans. Compounds 9 and 10 showed antifungal activity against C. neoformans, with the lowest minimal inhibitory concentration (MIC) of 12.5-25.0 µg/mL, whereas none of the compounds showed antifungal activity against C. albicans.

Development and characterization of a superabsorbing hydrogel film containing Ulmus davidiana var. Japonica root bark and pullulan for skin wound healing.

Ulmus davidiana var. japonica (UD) has widely been used in Korean traditional medicine for the treatment of various types of diseases including inflammation and skin wounds. The UD root bark powders possess gelling activity with an excellent capacity for absorbing water. This distinct property could make the UD root bark powders to be a great material for manufacturing a gel film specifically for the healing of large and highly exudating wounds (e.g., pressure sores and diabetic ulcers). In this research, we separated the UD root bark powder into 4 different samples based on their sizes and then tested their water absorption capacity and flowability. Based on these results, 75-150 µm sized and below 75 µm sized samples of UD root bark powders were chosen, and UD gel films were prepared. The UD gel films showed good thermal stability and mechanically improved properties compared with pullulan only gel film with excellent swelling capacity and favorable skin adhesiveness. Further, in the animal studies with the skin wound mice model, the UD gel films exhibited significant therapeutic effects on accelerating wound closure and dermal regeneration. Overall, this study demonstrated the applicability of UD root bark powders for hydrogel wound dressing materials, and the potential of UD gel films to be superior wound dressings to currently available ones.

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.

(-)-Catechin-7-O-ß-d-Apiofuranoside Inhibits Hepatic Stellate Cell Activation by Suppressing the STAT3 Signaling Pathway.

Hepatic fibrosis is characterized by the abnormal deposition of extracellular matrix (ECM) proteins. During hepatic fibrogenesis, hepatic stellate cell (HSC) activation followed by chronic injuries is considered a key event in fibrogenesis, and activated HSCs are known to comprise approximately 90% of ECM-producing myofibroblasts. Here, we demonstrated that (-)-catechin-7-O-ß-d-apiofuranoside (C7A) significantly inhibited HSC activation via blocking the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This is the first study to show the hepatic protective effects of C7A with possible mechanisms in vitro and in vivo. In our bioactivity screening, we figured out that the EtOH extract of Ulmusdavidiana var. japonica root barks, which have been used as a Korean traditional medicine, inhibited collagen synthesis in HSCs. Four catechins isolated from the EtOAc fraction of the EtOH extract were compared with each other in terms of reduction in collagen, which is considered as a marker of hepatic protective effects, and C7A showed the strongest inhibitory effects on HSC activation in protein and qPCR analyses. As a possible mechanism, we investigated the effects of C7A on the STAT3 signaling pathway, which is known to activate HSCs. We found that C7A inhibited phosphorylation of STAT3 and translocation of STAT3 to nucleus. C7A also inhibited expressions of MMP-2 and MMP-9, which are downstream genes of STAT3 signaling. Anti-fibrotic effects of C7A were evaluated in a thioacetamide (TAA)-induced liver fibrosis model, which indicated that C7A significantly inhibited ECM deposition through inhibiting STAT3 signaling. C7A decreased serum levels of aspartate amino transferase and alanine transaminase, which were markedly increased by TAA injection. Moreover, ECM-associated proteins and mRNA expression were strongly suppressed by C7A. Our study provides the experimental evidence that C7A has inhibitory effects on HSC activation after live injury and has preventive and therapeutic potentials for the management of hepatic fibrosis.

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.

Structural and rheological properties of pectic polysaccharide extracted from Ulmus davidiana esterified by succinic acid.

The present study was carried out to investigate the physicochemical and structural properties of pectic polysaccharide extracted from Ulmus davidiana (UDP) and to determine the physicochemical, structural, and rheological properties of esterified UDP with succinic acid (ES-UDP). The results indicated that UDP had high amounts of galacturonic acids and various neutral sugars, such as galactose, rhamnose, and glucose. UDP was identified as a low methoxyl pectin, consisting of 1,4-linked α-d-GalpA (the main backbone chain), supported by the results of Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, and 1D Nuclear magnetic resonance (NMR) spectroscopy. In the FT-IR and XRD, no difference was detected between UPD and ES-UDPs. However, 1H and 13C NMR spectra revealed that the new ester bonds were formed between a hydroxyl group of UDP and a carboxyl group of succinic acid during esterification. In the steady shear rheological analysis, the consistency index (K) of ES-UDP was significantly higher than that of UDP and increased significantly with increasing concentration of succinic acid. In the dynamic rheological analysis, the tan δ values of all ES-UDP solutions were significantly lower than those of the UDP solution.

Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis. MATERIALS AND METHODS: Cytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells. RESULTS: UDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death. CONCLUSIONS: From our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.

Transcriptomic characterization of gall tissue of Japanese elm tree (Ulmus davidiana var. japonica) induced by the aphid Tetraneura nigriabdominalis.

Insect galls are abnormal plant tissues induced by parasitic insect(s) for use as their habitat. In previous work, we suggested that gall tissues induced by the aphid Tetraneura nigriabdominalis on Japanese elm trees are less responsive than leaf tissues to jasmonic acid (JA), which is involved in the production of volatile organic compounds as a typical defensive reaction of plants against attack by insect pests. A comprehensive analysis of gene expression by RNA sequencing indicated that the number of JA responsive genes was markedly lower in gall tissues than in leaf tissues. This suggests that gall tissues are mostly defective in JA signaling, although JA signaling is not entirely compromised in gall tissue. Gene ontology analysis sheds light on some stress-related unigenes with higher expression levels in gall tissues, suggesting that host plants sense aphids as a biotic stress but are defective in the JA-mediated defense response in gall tissues.

Effects of herbal medicine on human uterine tumor-bearing nude mice.

AIM: Uterine leiomyomas are the most common benign uterine neoplasms associated with significant morbidity. Herbal formulas capable of restoring yin-yang balance by dispersing blood stasis may be useful for managing fibroid symptoms. MATERIALS AND METHODS: In this study, the antitumor properties of three herbs viz., Trogopterus xanthipes Milen-Edwards, Paeonia lactiflora Pallas, and Ulmus davidiana Planch were evaluated in nude mice injected intravenously with human malignant myomas. Tumor fragments were xenografted subcutaneously through a flank incision in female mice. The mice entered the study for 8 weeks when their tumors reached the threshold volume (260 mm3). The mice were randomly allocated to receive subcutaneous injections of normal saline (Group 1; negative control), P. lactiflora Pallas (Group 2), U. davidiana Planch (Group 3), T. xanthipes Milen-Edwards (Group 4), and intravenous injections of paclitaxel (Group 5; positive control). The weight and tumor volume were measured, followed by histopathology. RESULTS: A few cases of abdominal distention and death were observed in the negative control group. Furthermore, a considerable enlargement of the liver and spleen was observed in the negative control group at autopsy with a gradual increase in body weight during the experiment. The mean tumor volume which increased in negative control mice reduced in mice treated with herbal remedies or paclitaxel from day 14 onwards (P < 0.05). The degree of necrosis and apoptosis induction from herbal treatments was similar to that of paclitaxel. CONCLUSION: Collectively, three herbs viz., T. xanthipes Milen-Edwards, P. lactiflora Pallas, and U. davidiana Planch were able to induce necrosis and apoptosis of uterine leiomyoma cells, proving antitumor properties against uterine fibroids.

Ulmus davidiana ethanol extract inhibits monocyte adhesion to tumor necrosis factor-alpha-stimulated endothelial cells.

BACKGROUND: Ulmus davidiana var. japonica Rehder (UD) has long been used in traditional folk medicine in Asia. This study is designed to investigate the antiadhesive activity of the ethanol extract of UD (UDE) and its underlying mechanisms in cultured endothelial cells. METHODS: The dried root bark of UD was extracted with 80% (v/v) ethanol. The antiadhesive activity of the UDE was investigated in cultured human umbilical vein endothelial cells and human embryonic kidney epithelial 293T (HEK 293T) cells stably transfected with pGL3-vascular cell adhesion molecule (VCAM)-1-luc. Monocyte adhesion in endothelial cells was induced by tumor necrosis factor-alpha (TNF-α), and the protective effects of UDE on monocyte-endothelial cell adhesion, VCAM-1 expression, reactive oxygen species production, and nuclear factor-κB activity were determined. RESULTS: Exposure to UDE at a concentration of 3-30 µg/mL for 24 hours produced no detectable cytotoxicity in human umbilical vein endothelial cells, but it significantly inhibited TNF-α-induced monocyte adhesion and VCAM-1 expression. TNF-α treatment of HEK 293T/VCAM-1-luc cells resulted in increased luciferase activity of the VCAM-1 promoter, which was inhibited by treatment with UDE. Additionally, TNF-α-induced reactive oxygen species generation, nuclear translocation of nuclear factor-κB, and IκBα degradation in human umbilical vein endothelial cells were effectively reduced by treatment with 30 µg/mL of UDE. CONCLUSION: Our results indicated that UDE treatment inhibited TNF-α-induced monocyte adhesion in endothelial cells, suggesting that UD may reduce vascular endothelial inflammation.