Chemical Constituents， Pharmacological Effect， and Product Development of Eucommia ulmoides with Both Medicinal and Edible Values： A Review / 中国实验方剂学杂志

Eucommia ulmoides， a plant belonging to Eucommiaceae， has a history of medical use for over two thousand years in China. The dried bark and leaves of this plant are usually used as medicinal materials. Due to the high safety in clinical application， E. ulmoides leaves were officially recognized for both medicinal and edible use by the food safety evaluation in 2019， providing a valuable resource for the development of food and health products. According to the traditional Chinese medicine theory， E. ulmoides has the effects of nourishing the liver and kidneys， strengthening sinews and bones， and calming fetus. Modern research has shown that different parts such as the bark， leaves， flowers， and seeds of E. ulmoides contain similar chemical components， including phenylpropanoids， terpenoids， flavonoids， phenolic acids， steroids， and polysaccharides. E. ulmoides exhibits diverse pharmacological activities such as lowering blood pressure and blood lipid and glucose levels， preventing osteoporosis and possesses anti-tumor， anti-bacterial， antiviral， anti-inflammatory， antioxidant， and hepatoprotective effects. Therefore， it holds great potential for the development of products with both medicinal and edible values. This review systematically summarizes the chemical constituents， pharmacological activities， and representative medicinal and edible products of different parts of E. ulmoides. It is expected to provide theoretical references for the clinical application of E. ulmoides and its active components and the development and utilization of the products with both medicinal and edible values. This review contributes to a deeper understanding of the medicinal properties of E. ulmoides and provides guidance for further exploration of its applications in the healthcare field. As a plant with both medicinal and edible values， E. ulmoides is expected to attract more attention in future research and contribute to human health.

Pharmacokinetic study about compatibility of Eucommia ulmoides and Psoralea corylifolia / 中草药·英文版

OBJECTIVE@#The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study.@*METHODS@#Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo.@*RESULTS@#Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC0-24h and AUC0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed.@*CONCLUSION@#In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.

Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition / 中国中药杂志

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.

Assay of amino acids in leaves of Eucommia ulmoides under arbor forest mode and leaf-oriented cultivation mode by pre-column derivatization HPLC / 中国中药杂志

This study aims to develop the pre-column derivatization high performance liquid chromatography(HPLC) method for the determination of 16 kinds of amino acids in Eucommia ulmoides leaves, and compare the content of amino acids in the leaves harvested at different time and under leaf-oriented cultivation mode(LCM) and arbor forest mode(AFM). The HPLC conditions are as below: phenyl isothiocyanate(PITC) as pre-column derivatization agent, Agilent ZORBAX C_(18 )column(4.6 mm×250 mm, 5 μm), mobile phase A of acetonitrile-water(80∶20), mobile phase B of 0.1 mol·L~(-1) sodium acetate solution-acetonitrile(94∶6), gradient elution, flow rate of 1.0 mL·min~(-1), injection volume of 5 μL, column temperature of 40 ℃, and detection wavelength of 254 nm. The HPLC profile indicated well separation of 16 kinds of amino acids and the amino acid content in E. ulmoides leaves was up to 16.26%. In addition, the amino acid content in leaves of E. ulmoides under LCM was higher than under AFM. The amino acid content varied with the harvesting time. Through orthogonal partial least squares discriminant analysis, the amino acids of E. ulmoides under LCM and AFM were compared, which can distinguish the leaves under LCM from those under AFM. Principal component analysis was applied to comprehensively score the amino acids of E. ulmoides leaves. The results showed that the score of leaves under LCM was higher than that under AFM. Nutritional evaluation results indicated that the proteins in E. ulmoides leaves belonged to high-quality vegetable proteins. The established method for the determination of amino acid content is reliable. With the amino acid content as index, the leaf quality of E. ulmoides under LCM is better than that under AFM. This study lays a theoretical basis for the promotion of LCM for E. ulmoides and the development of medicinal and edible products from E. ulmoides leaves.

Eucommia ulmoides extract attenuates angiotensin II-induced cardiac microvascular endothelial cell dysfunction by inactivating p53

Abstract Angiotensin II (AngII) causes endothelial dysfunction. Eucommia ulmoides extract (EUE) is documented to manipulate AngII, but its impact on cardiac microvascular endothelial cell (CMVEC) function remains unknown. This study determines the effects of EUE on AngII-treated CMVECs. CMVECs were treated with different concentrations of AngII or EUE alone and/or the p53 protein activator, WR-1065, before AngII treatment, followed by examinations of the apoptotic, migratory, proliferative, and angiogenic capacities and nitric oxide (NO), p53, von Willebrand factor (vWF), endothelin (ET)-1, endothelial NO synthase (eNOS), manganese superoxide dismutase (MnSOD), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) levels. AngII induced CMVEC dysfunction in a concentration-dependent manner. EUE enhanced the proliferative, migratory, and angiogenic capacities and NO, MnSOD, and eNOS levels but repressed apoptosis and vWF and ET-1 levels in AngII-induced dysfunctional CMVECs. Moreover, AngII increased p53 mRNA levels, p-p53 levels in the nucleus, and p53 protein levels in the cytoplasm and diminishes HIF-1α and VEGF levels in CMVECs; however, these effects were counteracted by EUE treatment. Moreover, WR-1065 abrogated the mitigating effects of EUE on AngII-induced CMVEC dysfunction by activating p53 and decreasing HIF-1α and VEGF expression. In conclusion, EUE attenuates AngII-induced CMVEC dysfunction by upregulating HIF-1α and VEGF levels via p53 inactivation

Anti-inflammatory effect of couplet medicinals of Achyranthes bidentata -Eucommia ulmoides on mouse macro phage RAW264.7 / 中国药房

OB JECTIVE To study the anti-inflammatory effect of couplet medicinals of Achyranthes bidentata -Eucommia ulmoides. METHODS Mouse macrophage RAW 264.7 were divided into blank group ，model group ，A. bidentata group（800 μg/mL），E. ulmoides group（800 μg/mL）and low- ，medium- and high- concentration groups of couplet medicinals of A. bidentata - E. ulmoides （400，800，1 600 μg/mL）. Excep for blank group and model group ，the other groups were added with corresponding drugs for 6 hours；then blank group was continued to add into the medium ，while model group was added into 10 μg/mL lipopolysaccharide （to induce the inflammatory model ）；other groups were added into corresponding drugs and 10 μ g/mL lipopolysaccharide. The levels of inflammatory factors [nitric oxide （NO），interleukin-1β（IL-1β），IL-6，tumor necrosis factor-α （TNF-α）] were detected ，and Jin ’s formula was used to evaluate the effects of A. bidentata -E. ulmoides . The expression of inducible nitric oxide synthase （iNOS），cyclooxygenase-2（COX-2），nuclear factor kappa-B （NF-κB）and inhibitor α of NF-κB （IκBα）as well as the phosphorylation of NF-κB p65，IκB kinase（IKK），p38 mitogen-activated protein kinase （p38 MAPK）， extracellular signal-regulated kinase （ERK）and c-Jun N-terminal kinase （JNK）were determined. RESULTS Compared with blank group，the level of inflammatory factors ，protein expression of iNOS and COX- 2 as well as the phosphorylation of NF-κB p65， IKK，p38 MAPK，ERK and JNK were increased significantly （P＜0.01），while the protein expression of IκBα was decreased significantly（P＜0.01）. After intervention of couplet medicinals of A. bidentata -E. ulmoides ，the level of inflammatory factors ，the expression or phosphorylation of above proteins were reversed significantly （P＜0.05 or P＜0.01），and couplet medicinals of A. bidentata-E. ulmoides had a synergistic effect. CONCLUSIONS The couplet medicinals of A. bidentata -E. ulmoides have synergistic anti-inflammatory effect on RAW 264.7 cells. Its mechanism may be related to the inhibition of NF-κB/MAPK signaling pathway related protein expression.

Study on the effects and mechanism of saltwater stir-baked Eucommia ulmoides on kidney-yang deficiency in rats / 中国药房

OBJECT IVE To study the effects and potential mechanism of saltwater stir-baked Eucommia ulmoides on kidney-yang deficiency in rats. METHODS Ninety SD rats were randomly divided into normal control group （15 rats） and modeling group （75 rats）. Modeling group was given adenine intragastrically to establish kidney-yang deficiency model. After modeling，modeling group were randomly divided into model group ，positive control group （Guifu dihuang tablet 2.5 g/kg）， low-dose，medium-dose and high-dose groups of saltwater stir-baked E. ulmoides （1.5，3，6 g/kg），with 15 rats in each group. Administration groups were given relevant medicine intragastrically ，normal control group and model group were given normal saline intragastrically ，once a day ，for consecutive 8 weeks. The body weight of rats was measured before modeling and after medication. The score of kidney-yang deficiency syndrome was performed after medication. The levels of blood urea nitrogen （BUN），serum creatinine （SCR），testosterone（T）and cortisol （COR）in serum and superoxide dismutase （SOD）activity， malondialdehyde（MDA）level in renal tissue were detected. The pathological changes of renal tissue were observed after HE staining. Relative expressions of hypoxia-inducible factor- 1 α（HIF-1 α）and signal transducer and activator of transcription 5 （STAT5） mRNA in renal tissue were detected by RT-PCR. The relative expressions of HIF- 1α，STAT5 and phosphorylated STAT 5 （p-STAT5）protein and the ratio of gray values of p-STAT 5 and STAT 5（p-STAT5/STAT5）in renal tissue were detected by Western blot. RESULTS Before modeling ，there was no statistical significance in body weight of rats in each group （P＞0.05）. After medication， compared with model group ， pathological changes of renal tissue were all recovered in saltwater stir-baked E. ulmoides groups and positive control group ， while body weight ，the level of T in serum and SOD activity qq.com in renal tissue were all increase d significantly （P＜0.05）. The scores of kidney-yang deficiency syndrome ，levels of BUN ， SCR and COR in serum ，MDA level in renal tissue ，the relative expressions of HIF- 1α and STAT5 mRNA，the relative expressions of HIF- 1α，STAT5 and p-STAT 5 protein as well as p-STAT5/STAT5 were all significantly decre ased （P＜0.05）. The above effects of saltwater stir-baked E. ulmoides were in dose-dependent manner （P＜0.05）. CONCLUSIONS Saltwater stir-baked E. ulmoides can significantly relieve renal tissue damage in rats with kidney-yang deficiency ，decrease the levels of BUN ，SCR and COR in serum ，increase the level of T in serum ，the mechanism of which may be associated with anti-oxidative stress and inhibition of the expression of HIF- 1α and STAT5 protein.

Optimization of Ultrafiltration Technology of Enzymatic Hydrolysate from Eucommia ulmoides Peel / 中国药房

OBJECTIVE：To optim ize the ultrafiltration technology of enzymatic hydrolysate from Eucommia ulmoides peel. METHODS：The single factor test was adopted to investigate the effects of molecular weight of ultrafiltration membrane ，liquid temperature，operating pressure ，operating frequency ，membrane filtration time ，liquid concentration and pH on transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel. Setting the molecular cut off of fixed ultrafiltration membrane of 100 000，liquid concentration of 7 g/L，and pH value of 7，the ultrafiltration technology was optimized by Box-Behnken design response-surface methodology and validated with liquid temperature ，operating pressure，operating frequency and membrane passing time as factors ，using comprehensive scores calculated from transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate as indexes. RESULTS ：The optimal ultrafiltration technology of enzymatic hydrolysate from E. ulmoides peel was as follows as liquid temperature of 35 ℃，operating pressure of 0.5 MPa，operating frequency of 35 Hz and membrane passing time of 42 min. Results of validation tests showed that the comprehensive scores of the transfer rates of aucubin ，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel was 78.06％（RSD＝1.43％，n＝3），and its relative error with the predicted value （77.18％） was 1.14％. CONCLUSIONS ：The optimized ultrafiltration technology is stable and reliable ，and can be used for the ultrafiltration purification of enzymatic hydrolysate from E. ulmoides peel.

Comparative Study on Ancient and Modern Prescriptions Containing Eucommia ulmoides / 中国药房

OBJECTIVE：To comp are the meridian tropism of compatible herbs and compatibility rules of ancient and modern prescriptions containing Eucommia ulmoides ，and to provide theoretical basis for modern clinical application of E. ulmoides . METHODS：Ancient prescriptions containing E. ulmoides were screened from Dictionary of TCM Prescription . The prescriptions containing E. ulmoides were screened from clinical trials which published in CNKI ，Wanfang database and VIP during Jan. 2000 to Jan. 2020. Data mining methods such as frequency statistics and Apriori algorithm were used to analyze the main diseases of ancient and modern prescriptions containing E. ulmoides and the use frequency ，types，meridian tropism and compatibility rules of medical materials. RESULTS ：A total of 84 ancient prescriptions and 188 modern prescriptions of E. ulmoides were included. Ancient prescriptions were mainly used to treat diseases such as back pain ，deficiency，threatened abortion. Modern prescriptions were mainly used to treat osteoarthropathy （mainly lumbar intervertebral disc herniation ），gynecological diseases ，cardiovascular diseases. Cinnamomum cassia ，Angelica sinensis and Achyranthes bidentatawerethe were the high-frequency compatible herbs in ancient prescriptions with E. ulmoides ，and were tonifying medicine ，dispelling wind and dampness medicine and clearing heat medicine；compatible herbs were mainly of warm property ，and the channel tropism was mostly kidney meridian and liver meridian；the five tastes of compatible herbs were mainly sweet and spicy. A. sinensis ，Glycyrrhiza uralensis and Rehmanniae Radix Praeparata were the high-frequency compatible herbs in modern prescriptions with E. ulmoides ，and were mainly tonic medicine，anti-rheumatic medicine ，medicine for promoting blood circulation and removing blood stasis ；compatible herbs were mainly of warm property ，and the channel tropism was mostly liver meridian and kidney meridian ；the five tastes of medicine were mainly bitter and spicy. By analyzing the Apriori association rules of high-frequency herbs ，a total of 10 core herbs combinations were obtained in ancient prescriptions ，including 8 third-order association rules and 2 fourth-order association rules ；a total of 11 core herbs combinations were obtained in modern prescriptions ，including 3 third-order association rules and 8 fourth-order association rules. CONCLUSIONS ： Ancient and modern prescriptions containing E. ulmoides are mainly used to treatlumbar disease ， followed by obstetrics and gynecology com diseases. In addition ，the modern prescriptions can also be #used for the treatment of cardiovascular and cerebrovascular diseases. The ancient prescriptions mainly focus on warming and tonifying ，while the modern prescriptions are more compatible with medicine for dispelling wind and dampness and medicine for promoting blood circulation and removing blood stasis on the basis of tonifying deficiency ；most of the medicines in ancient prescriptions contribute in kidney and liver meridians ，mainly sweet and pungent ，while most of the medicines in modern prescriptions contribute in liver meridian ，and are more compatible with bitter medicines.

Identification and Expression Analysis of TIFY Transcription Factor in Eucommia ulmoides / 中国实验方剂学杂志

Objective:To identify the TIFY gene family in <italic>Eucommia ulmoides</italic> and analyze its expression from the whole genome level to lay the foundation for further study on <italic>EuTIFYs</italic> gene function. Method:Based on the <italic>E. ulmoides</italic> genome database，the TIFY gene family was identified through bioinformatics analysis tools such as National Center for Biotechnology Information（NCBI），MEME，PlantCare，Expert Protein Analysis System（ExPASy），and TBtools. Physicochemical properties，phylogenetic evolution，gene structure，<italic>cis</italic>-acting elements of the promoters and their expression patterns in leaf development and gum formation of the gene family were systematically analyzed. Result:In this study，fourteen <italic>EuTIFY</italic> genes （<italic>EuTIFY1</italic>-<italic>EuTIFY14</italic>） were identified in the <italic>E. ulmoides</italic> genome. The <italic>EuTIFYs</italic> were composed of 312-1 074 bp nucleotides encoding 102-357 amino acid residues，with isoelectric points of 4.99-10.06 and molecular weight in the range of 10.8-39.14 kDa. According to putative subcellular localization，proteins，which were mainly hydrophilic proteins，localized in the nucleus. The 14 <italic>EuTIFYs</italic> were unevenly distributed on 13 chromosomes. <italic>EuTIFY</italic> gene family was divided into four subfamilies： <italic>TIFY</italic>，<italic>JAZ</italic>，<italic>ZML</italic>，and <italic>PPD</italic>，which contained three，four，five，and two members respectively. The promoters of <italic>EuTIFYs</italic> contained multiple photoperiodic and abiotic stress-responsive cis-acting elements，which were involved in plant growth and abiotic stress regulation. Expression pattern analysis showed that <italic>EuTIFYs </italic>exhibited different expression levels in different development stages of <italic>E. ulmoides</italic> leaves and multiple interactions，and most of the genes were highly expressed in the early stage of leaf development and positively regulated the formation of <italic>E. ulmoides</italic> gum. Conclusion:Fourteen <italic>EuTIFYs</italic> were identified from the whole genome of <italic>E. ulmoides</italic>，and their structural characteristics and expression patterns were analyzed by bioinformatics. The findings of this study are expected to provide references for further research on the function of <italic>EuTIFYs</italic>.

Effect of Processing Technology on the Quality of Eucommia ulmoides and Recent Advances in Study on Its Chemical Composition and Pharmacology / 中国药学杂志

Eucommiae Cortex is a kind of traditional Chinese medicine. Its raw products and salt-processed products are often used to nourish liver and kidney and strengthen muscles and bones. Based on systematic study of literature, this paper summarizes the influence of processing technology on the quality of Eucommia ulmoides, as well as recent research progress in the chemical components and pharmacological effects of Eucommia ulmoides, in order to lay a foundation for the research of normalization and standardization of Eucommia ulmoides decoction pieces.

Effect of Eucommia ulmoides Polysaccharide on db/db Diabetic Mice's Glycolipid Metabolism / 中国药学杂志

OBJECTIVE: To investigate the effect and mechanism of Eucommia ulmoides polysaccharide (EUP) on db/db diabetic mice's glycolipid metabolism. METHODS: The db/db type 2 diabetes mice model were randomly divided into model control group, EUP low, middle and high dose group and positive control metformin group,-+/db mice of the same age were set as normal control group. The mice were weighed, and the changes of fasting blood glucose (FBG), blood lipid (TG, TC, LDL-C, HDL-C), interleukin (IL-8, IL-1β, IL-6), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were detected after drug delivery for 9 weeks. HE staining and oil red O staining were used to evaluate the pathological changes and steatosis of liver in mice. Western blot assay were used to detect the protein expressions of NF-κB p65 and HO-1 in liver tissues of mice. RESULTS: EUP could reduce the body weight of db/db mice, reduce the levels of FBG, TG, TC, LDL-C, IL-8, IL-1β, IL-6, MDA, NF-κB p65 proteins and increase the levels of HDL-C and HO-1 proteins. EUP could alleviate pathological changes and steatosis of liver in db/db mice. CONCLUSION: The obesity, hyperglycemia, hyperlipidemia and liver injury of db/db mice with type 2 diabetes are all improved by EUP, and the mechanism is related to the regulation of inflammatory response and oxidative stress.

Molecular mechanism of eucommia ulmoides active ingredients treating synovitis of knee osteoarthritis: An analysis based on network pharmacology / 中国组织工程研究

BACKGROUND: Studies have shown that the active ingredients of Eucommia ulmoides can inhibit the growth of synovial fibroblasts of arthritis, but the molecular mechanism underlying Eucommia ulmoides treating synovial inflammation of knee osteoarthritis is not yet clear. OBJECTIVE: To investigate the possible molecular mechanism of Eucommia ulmoides ingredients treating synovitis of knee osteoarthritis based on the network pharmacology and bioinformatics. METHODS: The active ingredients and targets of Eucommia ulmoides were screened by using the TCM systematic pharmacological analysis platform (TCMSP). The disease targets corresponding to synovitis of knee osteoarthritis were obtained from Gene Expression Omnibus (GEO). The protein-protein interaction network was constructed by STRING online database, analyzed and showed by the Cytoscape software. Gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of the targets were conducted by R/Bioconductor. The enrichment results were obtained with a significant difference (P < 0.05). RESULTS AND CONCLUSION: A total of 21 active ingredients of Eucommia ulmoides, including eugenol, eucommia glycoside, eucommia liposide A, quercetin, and 25 different expressed genes (7 up-regulated and 18 down-regulated differentially expressed genes) were obtained. The main biological processes of the differentially expressed genes were found different significantly in cytokine activity, cytokine receptor binding and activating transcription factor binding. The hub genes, such as interleukin-6, vascular endothelial growth factor A and chemotactic factor 8, may be regulated by the active ingredients to influence the signal of MAPK/NF-kappa B/Toll-like receptor signaling pathway. Based on the network pharmacology and bioinformatics approach, the study preliminarily validates the molecular mechanism of Eucommia ulmoides for treatment of synovitis of knee osteoarthritis, which may lay a foundation for further pharmacodynamics study and experiment.

Alcohol extract of eucommia ulmoides oliv. Promotes bone healing in rats with periapical periodontitis / 中国组织工程研究

BACKGROUND: Current research on Eucommia ulmoides Oliv. mainly focuses on its use in the treatment of osteoarthritis that Eucommia ulmoides Oliv. can enhance the healing ability of bone tissue. However, research on its bone repair ability in periapical periodontitis has not been reported. OBJECTIVE: To study the effect of alcohol extract of Eucommia ulmoides Oliv. on cathepsin K expression in periapical periodontitis rats. METHODS: Twenty-four Sprague-Dawley rats were divided into normal control group (n=4) and apical periodontitis group (n=20). In the periapical periodontitis group, a periapical periodontitis model was established after exposure of the dental pulp in the first molar of the right mandible. The normal control group did not deal with any treatment. After 4 weeks of feeding, four rats from each group were taken for micro-CT detection. Bone destruction was quantified to confirm whether the rat model of periapical periodontitis was successfully constructed. After 5 weeks of feeding, the remaining 16 rats with periapical periodontitis were equally randomized into alcohol extract group (given alcohol extract of Eucommia ulmoides Oliv. via intragastric administration, 5 mL/kg per day) and normal saline group (given the same dose of normal saline via intragastric administration every day). After 4 weeks of gavage, four mice from each group were selected to perform micro-CT examination. The ability of alcohol extract of Eucommia ulmoides Oliv. to repair periapical bone tissue was analyzed. First molars of the right mandible from the other four rats in each group were extracted to detect the expression of cathepsin K in the alveolar bone using immunohistochemical staining. RESULTS AND CONCLUSION: Micro-CT results showed that the rat model of periapical periodontitis was successfully constructed as there was a significant difference in the bone resorption volume between the normal control and apical periodontitis groups [(0.223±0.009) mm3 vs. (0.945±0.037) mm3, P=0.00]. After 4 weeks of gavage, the micro-CT results showed that the alcohol extract of Eucommia ulmoides Oliv. significantly reduced the bone resorption volume in the rat model of periapical periodontitis (P < 0.05). Immunohistochemistry results showed that the alcohol extract of Eucommia ulmoides Oliv. significantly inhibited the expression of cathepsin K, a marker of bone destruction, in the rat model of periapical periodontitis. Therefore, these findings indicate that the alcohol extract of Eucommia ulmoides Oliv. can inhibit the expression of cathepsin K and promote the healing of bone tissue in the rats with periapical periodontitis.

Simultaneous Determination of Contents of 8 Components in Eucommia ulmoides Leaves by HPLC / 中国药房

OBJECTIVE： To establish content determination method for simultaneously determining aucubin，geniposidic acid，catechin，chlorogenic acid，asperuloside，rutin，isoquercitrin and astragalin in Eucommia ulmoides leaves. METHODS：HPLC method was adopted. The determination was performed on Agilent ZORBAX SB-C18 column with the mobile phase consisted of acetonitrile-0.1％ phosphoric acid（gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 203 nm for aucubin and catechin，239 nm for geniposidic acid and asperuloside，220 nm for chlorogenic acid，354 nm for rutin and isoquercitrin，and 266 nm for astragalin. The sample size was 5 μL. RESULTS： The linear range of aucubin， geniposidic acid， catechin， chlorogenic acid， asperuloside， rutin， isoquercitrin and astragalin were 0.812-6.090 μg（r＝0.999 3），0.438-3.285 μg（r＝0.999 2），0.045-0.336 μg（r＝0.999 2），0.882-6.615 μg（r＝0.999 3），0.097-0.726 μg（r＝0.999 1），0.064-0.483 μg（r＝0.999 3），0.048-0.360 μg（r＝0.999 1） and 0.014-0.108 μg（r＝0.999 7），respectively. RSDs of precision， stability and reproducibility tests were all lower than 3.5％（n＝6）. The average recovery rates were 101.60％，103.06％，99.77％，96.93％，98.17％，96.75％，98.97％ and 99.60％，with RSDs of 1.42％，2.65％，2.78％，2.05％，2.26％，0.93％，2.79％ and 3.08％，respectively（n＝6）. The contents of aucubin， geniposide， catechin， chlorogenic acid， plantain， rutin， isoquercetin and astragaloside in 12 batches of E. ulmoides leaves from different collection time and planting varieties were 10.903-17.245， 5.578-7.892， 0.198-0.440， 13.890-19.782， 1.008-1.547， 1.102-2.396， 0.267-0.701， 0.150-0.412 mg/g， respectively. The content fluctuated greatly. The contents of aucubin， geniposide， catechin， chlorogenic acid， rutin and pinoresinol diglucoside in cortex of E. ulmoides were 0.299， 0.123， 0.580， 0.112， 0.026，1.961 mg/g， respectively. CONCLUSIONS： The method is simple， reproducible and accurate. It can be used to evaluate the quality of E. ulmoides leaves. There are obvious differences in composition and content of components in different medicinal parts （cortex， leaves） of E. ulmoides.

Enhanced Antioxidant and Anticancer Properties of Processed Eucommiae Cortex

Eucommiae Cortex (EC), bark of Eucommia ulmoides, has been known as a traditional medicine to regulate hypertension and immune system. Because silk of gum in the EC blocks the release of active ingredients, EC generally has been utilized after processing with carbonization or salt-water to breakdown it. This study aimed to investigate the differences of non-processed EC and processed EC on antioxidant and anticancer properties. Antioxidant capacity was assessed by measuring the content of total polyphenols, reducing power, and ABTS radical scavenging effect. And anticancer effects were examined by evaluating the viability of pancreatic cancer cells and wound healing ability. The results demonstrated that processed EC contained more content of polyphenols and exhibited more potent reducing power and radical scavenging effect than non-processed EC. In addition, processed EC more efficiently inhibited proliferation and migration of pancreatic cancer cells. These results suggest that processing of medicinal plants can improve the biological properties such as antioxidant or anticancer activity, which may lead to the development of herbal medicine treatment technology.

Treating nonspecific low back pain by SET sling exercise therapy combined with tropical herb-Rattan Moxibustion liquid external rubbing therapy

Objective: To explore the clinical effects of tropical Eucommia ulmoides compound-Rattan Moxibustion liquid external rubbing therapy which is from medicine of Li Nationality in Hainan combined with SET sling exercise therapy technique and lumbar-abdominal muscle training program on treating nonspecific low back pain (NLBP) as well as its influence on serum 5-hydroxytryptamine and beta-endorphin levels. Methods: From June 2016 to June 2018, 42 NLBP patients were admitted to the outpatient and ward of Rehabilitation Department of the First Affiliated Hospital of Hainan Medical College, who were randomly divided into control group (n=21) and experimental group (n=21). On the basis of traditional massage manipulation, the control group adopts lumbar and abdominal muscles training, while Rattan Moxibustion liquid external rubbing therapy combined with SET sling exercise therapy was used in the experimental group. The treatment was given once every other day, three times a week and 20 min each time for 8 weeks. Then ODI index and VAS scale of low back pain, as well as serum 5-HT and beta-EP levels were observed and detected. Results: The improvement in low back pain index ODI index of the experimental group were better than that of the control group (control group from 21.23±1.57 to 4.78±0.86 while experiment group from 21.27±1.36 to 2.75±0.64 after 8 weeks' treatment)(P<0.05). VAS scale decreased significantly in the experiment group compared with control group (control group from 6.62±1.51 to 2.71±0.92 while experiment group from 6.71±1.55 to 1.83±0.79 after 8 weeks' treatment)(P<0.05). Serum 5-HT in the experimental group were significantly improved compared with those in the control group [control group from (70.15±20.64) ng/mL to (127.34±40.59) ng/mL while experiment group from (68.72±19.18) ng/mL to (142.65±38.72) ng/mL after treatment](P<0.05) and beta-EP level ameliorates compared with control group [control group from (180.63±51.87) pg/mL to (225.76±57.63) pg/mL while experiment group from (172.39±50.72) pg/mL to (251.26±62.89) pg/mL after treatment](P<0.05). Conclusions: Tropical herb-Rattan Moxibustion liquid external rubbing therapy combined with SET sling exercise therapy technology shows significant effects on NLBP. The mechanism may be related to the improved serum 5-HT and beta-EP levels.

Therapeutic effects and spectra-effect relationship of different extracts of Eucommia ulmoides on Parkinson’s disease mice / 中草药

Objective: To explore the therapeutic effects of different extracts of Eucommia ulmoides on Parkinson’s disease mice, as well as the relationship between ultra-high performance liquid chromatography (UPLC) fingerprint and treatment of Parkinson’s disease. Methods Through the mouse climbing test and the content of dopamine (DA) in the striatum of the brain, the therapeutic effect of different gradient ethanol extracts of E. ulmoides on Parkinson’s disease mice was observed. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze the fingerprints of different extracts of E. ulmoides. Combined with the results of climbing rod test and dopamine content, partial least squares regression (PLSR) analysis was used to establish the pharmacodynamic relationship between E. ulmoides and Parkinson’s disease. Results The 50% and 75% ethanol extracts of E. ulmoides could significantly shorten the climbing time. The 75% ethanol extract of E. ulmoides significantly increased the striatum dopamine content in the brain. The results of PLSR analysis showed that ulmoside, liriodendrin, 5-hydroxymethylfurfural, caffeic acid in E. ulmoides were closely related to climbing rod and dopamine content of mice. Conclusion The ethanol extract of E. ulmoides has anti-Parkinson’s disease effect, and the effect is most significant with 75% alcohol extract. The compounds of ulmoside, liriodendrin, 5-hydroxymethylfurfural, caffeic acid may be the main active ingredients of E. ulmoides in the treatment of Parkinson’s disease.

Chemical constituents from barks of Eucommia ulmoides / 中草药

Objective: To study the chemical constituents of barks of Eucommia ulmoides. Methods: Compounds were isolated by means of normal phase silical gel, reverse phase ODS, Sephadex LH-20 column chromatography, and preparative-HPLC, and their structures were identified on the basis of various spectroscopic analyses, including NMR and HR-ESI-MS. Results: Nine known compounds, including seven flavonoids and two phenylpropanoids, were isolated from the 95% EtOH extract of barks of E. ulmoides. Their structures were identified as licoflavone B (1), 3,5,4’-trihydroxy-7,3’-dimethoxyflavone (2), liquiritigenin (3), formononetine (4), (+)-4’-O-methylglabridin (5), paratocarpin E (6), loureirin C (7), threo-1-(4-hydroxy-3-methoxyphenyl)-1-methoxy-2-{4-[1-formyl- (E)-vinyl]-2-methoxyphenoxy}-3-propanol (8), and diospyrosin (9). Conclusion: Compounds 1-9 are obtained from the genus of Eucommia for the first time.

Community composition and ecological functional structural analysis of endophytic fungi in bark of Eucommia ulmoides in different areas / 中国中药杂志

Based on high-throughput sequencing and metagenomic technology,the community composition and ecological functions of endophytic fungi in the bark of Eucommia ulmoides from three producing areas,Fengxiang town in Zunyi county of Guizhou province,Lingyang town of Cili county of Hunan province and Mumen town of Wangcang county of Sichuan province,were analyzed. A total of110 865 effective sequences of endophytic fungi were obtained in the study. The corresponding fungal group of OTUs after clustering belonged to 3 phyla( Ascomycota,Basidiomycota,Zygomycota),10 classes,25 orders,41 families,57 genera and 74 species. Among them,the dominant genera of Sichuan Wangcang Bark of E. ulmoides( EWP) was an unclassified genus in the Nectriaceae of the Crimsonaceae,with a relative abundance of 54. 79%; The dominant species of Hunan Cili Bark of E. ulmoides( ECP) was the unclassified genus of Ascomycota,with a relative abundance of 39. 97% and the dominant species of Guizhou Zunyi bark( EZP) was Lophiostoma,and its relative abundance was 47. 07%. The analysis of α diversity indicated that the shannon diversity index of endophytic fungi from different places was as follows: ECP: 1. 340 2>EZP: 1. 380 4 > EWP: 1. 168 3. The simpson diversity index was: EWP( 0. 427 3) >EZP( 0. 332 5) > ECP( 0. 313 6). FUNGuild software platform analysis displayed that endophytic fungi of E. ulmoides bark from three producing areas contained the following 14 functional groups: plant pathogen,animal pathogen and endophyte et al.,the number of functional groups in the 3 samples of E. ulmoides reached up 8 genera and exceeded one half of the total number. Correlation analysis of Canonical correspondence analysis( CCA) between endophytic fungal community diversity and four active compounds of E. ulmoides were analyzed,the results showed that the contents of pinoresinol diglucoside and chlorogenic acid,to a certain extend,had a positive correlation with an unclassified genus of Davidiellaceae,Mortierella,Chaetomium and Pestalotiopsis from the endophytic fungi in EWP sample.