The water extracts of Euonymus alatus (Thunb.) Siebold attenuate diabetic retinopathy by mediating angiogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus (Thunb.) Siebold (family Celastraceae) is a deciduous woody shrub that is recorded in ShenNong BenCaoJing. It has been widely used for diabetes in traditional Chinese medicine. AIM OF THE STUDY: This study aimed to identify the most effective extract of Euonymus alatus (EA) against high glucose-induced endothelial cells in vitro, evaluate its pharmacological effect on retinopathy in diabetic mice and explore its underlying mechanism by RNA sequencing. METHODS: Retinal vascular endothelial cells (RF/6A) were treated with normal glucose (5.5 mmol/L glucose), high glucose (25 mmol/L glucose) or high glucose plus methanol extracts of EA (MEA), ethyl acetate extracts of EA (EEA) or water extracts of EA (WEA). The cytotoxicity and cell viability were determined by Cell Counting Kit-8 (CCK-8) assay. Cell migration was examined using the Transwell assay, and tube formation ability was measured using the Matrigel assay. Then, the KK-Ay mice were administered WEA or water for 12 weeks. The velocities of ocular blood flow were determined by Doppler ultrasound. RNA sequencing and reverse transcription quantitative PCR (RT-qPCR) were performed on WEA-stimulated RF/6A cells to reveal the underlying mechanism. RESULTS: The cytotoxicity assay found that 30 µg/mL MEA, 20 µg/mL EEA and 30 µg/mL WEA had no toxic effect on RF/6A cells. The cell viability results showed that MEA, EEA and WEA all decreased cell viability. Compared with the high-glucose group, both MEA and WEA decreased the number of migrated cells, while the inhibition rate of WEA was higher. The Matrigel results showed that 30 µg/mL WEA effectively reduced the total tube length. Moreover, WEA improved the haemodynamics of the central retinal artery. RNA sequencing coupled with RT-qPCR verified that WEA regulated angiogenesis-related factors in high glucose-stimulated RF/6A cells. CONCLUSIONS: WEA inhibits the migration and tube formation of RF/6A cells and improves diabetic retinopathy (DR) by mediating angiogenesis.

Isolation and purification of flavonoids from Euonymus alatus by high-speed countercurrent chromatography and neuroprotective effect of rhamnazin-3-O-rutinoside in vitro.

The flavonoids from Euonymus alatus exhibit many biological activities including significant antioxidant, anti-inflammatory, anti-cancer. In this work, a high-speed countercurrent chromatography method for the isolation and purification of flavonoids from crude extracts of Euonymus alatus was established. The effects of several solvent systems on the separation efficiency of target compounds in the extract of Euonymus alatus were studied. The solvent system composed of n-hexane-ethyl acetate-methanol-water at a volume ratio of (3:5:3:5, v/v) was chosen, in which the lower phase was used as the mobile phase at the rotation speed of 800 rpm and flow rate of 2.0 mL/min. The three flavonoids were obtained and identified as patuletin-3-O-rutinoside, rhamnazin-3-O-rutinoside, and dehydrodicatechin A by mass spectroscopy and nuclear magnetic resonance, and the quantities of patuletin-3-O-rutinoside, rhamnazin-3-O-rutinoside, and dehydrodicatechin A were 2.2, 9.7, and 1.8 mg, respectively. The results indicated that high-speed countercurrent chromatography was a simple and efficient method for the isolation and purification of flavonoids from the crude extracts of Euonymus alatus. The cellular antioxidant activity experimental result indicated that rhamnazin-3-O-rutinoside could alleviate H2 O2 -induced oxidative stress.

Traditional uses, botany, phytochemistry, pharmacology, separation and analysis technologies of Euonymus alatus (Thunb.) Siebold: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus (Thunb.) Siebold (E. alatus), a well-known medicinal plant, has been widely used thousands of years in China for the treatment of various diseases such as urticaria, dysmenorrhea, wound, dysentery, blood stasis, rheumatism and arthritis. Due to the extensive application of E. alatus in the fields of ethnopharmacological usage, the pharmaceutical researches of E. alatus keeps deepening. AIM OF THE STUDY: This paper reviewed and summarized the integrated research progress of this medicinal plant. A comprehensive summary and comparison of traditional usages, botany, phytochemistry, pharmacology, toxicology, separation and analysis technologies of the E. alatus highlight recent scientific advances, which provides new insights into the research and development of this medicinal plant and would be helpful to promote the research situation of underlying pharmacological mechanisms and further utilizations of E. alatus. MATERIAL AND METHODS: Literature survey was carried out via classic books of herbal medicine, PhD. and MSc. Dissertations. Online scientific databases including Pubmed, SciFinder, Science Direct, Scopus, the Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI) and others were searched up to February 2020 to identify eligible studies. All literatures of the research subject are analyzed and summarized in this review. RESULTS: The E. alatus has been widely used in traditional practice in China, Korea and other Asian Countries. In the study of phytochemistry, more than 230 chemical constituents have been isolated and identified from E. alatus, including sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, phenylpropanoids, lignans, steroids, alkaloids and other compounds. Among them, literature reports show that flavonoids and steroids are the most important bioactive substances found in this plant. A number of researches also have shown that extracts and compounds from E. alatus exert a wide spectrum of pharmacological effects, including antidiabetic effect, anti-tumor effects, anti-inflammatory effects, hepatoprotective effects, antioxidant effects, antibacterial effects, as well as other effects. However, most of the studies without clinical research. Research into plant's toxicological effects has also been limited. In addition, this review also summarizes and compares the separation and analysis technologies of E. alatus. CONCLUSIONS: E. alatus has potential for the treatment of many diseases, especially tumors and diabetes. But many traditional uses of E. alatus have not been validated by current investigations. Additionally, modern studies haven't gone far enough into its pharmacological effects and the corresponding chemical constituents, more efforts should be made to illuminate the underlying mechanisms of E. alatus for treatment of tumors and diabetes. Moreover, the toxicological effects of this plant can be further studied. Currently, there are limited studies on its side effects and toxicological effects, which should provide further guidance for the safety of clinical use.

(3ß,16α)-3,16-Dihydroxypregn-5-en-20-one from the Twigs of Euonymus alatus (Thunb.) Sieb. Exerts Anti-Inflammatory Effects in LPS-Stimulated RAW-264.7 Macrophages.

To discover new pharmacologically active natural products, here, we performed the phytochemical analysis of a Korean medicinal plant. Euonymus alatus (Thunb.) Sieb. is a traditional medicinal plant that has been used as a remedy for various diseases in Asian countries. In particular, the cork cambium on the twigs of E. alatus has been used to treat dysmenorrhea, tumors, diabetes, and wound. Phytochemical analysis of the methanolic extract of E. alatus twigs led to the isolation of a sterol, which was identified as (3ß,16α)-3,16-dihydroxypregn-5-en-20-one (1) by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry. The stereochemistry of 1 was established with nuclear Overhauser effect spectroscopy (NOESY) analysis and comparison of electronic circular dichroism (ECD) data. To the best of our knowledge, the isolation of compound 1 from nature is first reported here, as well as the complete and revised NMR data assignment of 1. In lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages, compound 1 significantly inhibited nitric oxide (NO) production at an IC50 value of 12.54 ± 0.05 µM as well as the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, the pre-treatment with compound 1 attenuated the LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) p65 through the inhibition of the phosphorylation of IκB kinase alpha (IKKα), IKKß, and inhibitor of kappa B alpha (IκBα). Compound 1 also inhibited the LPS-induced phosphorylation of p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Taken together, compound 1 may serve as an anti-inflammatory constituent of E. alatus twigs and its anti-inflammatory property is thought to be associated with the inhibition of NO production via suppression of iNOS and COX-2 expression through inhibition of IKKα/ß, I-κBα and NF-κB p65 activation and downregulation of p38, JNK, and ERK mitogen-activated protein kinase signal pathways in RAW 264.7 macrophages. These findings also provide experimental evidence that compound 1 identified from E. alatus twigs could be a candidate for an anti-inflammatory agent.

MIX2: A Novel Natural Multi-Component Modulator of Multidrug-Resistance and Hallmarks of Cancer Cells.

Multidrug resistance is one of the key barriers suppressing the effectiveness of drug therapies of malignant tumors. Here, we report a study on the effect of a mix of natural extracts (MIX2) prepared from fresh fruits of Prunus spinosa, Crataegus monogyna, Sorbus aucuparia, and Euonymus europaeus on the classic hallmarks of cancer cells and the expression of multidrug resistance proteins. In the studies, HeLa and T98G cell lines, and classic methods of molecular biology, including RT-qPCR, Western blot, flow cytometry, and confocal imaging, were used. Additionally, migration, adhesion, and proliferation assays were performed. The obtained results indicate that the MIX2 cocktail presents strong anti-cancer properties. MIX2 is not toxic, but at the same time significantly alters the migration, proliferation, and adhesion of tumor cells. Furthermore, it was found that cells exposed to the mixture presented a significantly reduced expression level of genes associated with MDR, including ABCB1, which encodes for glycoprotein P. In vitro data showed that MIX2 effectively sensitizes tumor cells to doxorubicin. We postulate that modulation of the multidrug resistance phenotype of tumors with the use of MIX2 may be considered as a safe and applicable tool in sustaining drug delivery therapies of malignancies.

Enhancement of Glucose Utilization by Loesenerine through AMPK Activation in Myotubes.

Type 2 diabetes is characterized by hyperglycemia derived from insulin resistance in periphery tissue. Effects of skeletal muscle on glucose disposal are closely related to insulin resistance. The potential effects on mitochondrial function of loesenerine, a macrocyclic spermidine alkaloid from the aerial part of Euonymus fortunei (TURCZ.) HAND.-MAZZ were observed after a high-throughout screening based on mitochondrial membrane potential (MMP) assay. Further pharmacological studies revealed that loesenerine activates AMP-activated protein kinase (AMPK) pathway through increasing ADP/ATP ratio by inhibiting mitochondrial respiration. In addition, loesenerine induced 1.07-, 1.14-, and 1.22-fold increment of glucose uptake in C2C12 cells at the concentrations of 20, 40 and 80 µmol/L, respectively. Meanwhile, incubated with loesenerine for 12 h increased glucose consumption in a dose-dependent manner in C2C12 cells. This is the first report that macrocyclic spermidine alkaloid possesses potential hypoglycemic activity in vitro.

Novel Potent Hypoglycemic Compounds from Euonymus laxiflorus Champ. and Their Effect on Reducing Plasma Glucose in an ICR Mouse Model.

α-Glucosidase inhibitors (aGIs) have been used as an effective therapy for type-2 diabetes, which remains a global health issue. The aim of this study was to achieve bioactivity-guided isolation, identification and evaluation of hypoglycemic compounds from Euonymus laxiflorus Champ. trunk bark (ELCTB). Eleven active compounds were isolated and identified as walterolactone A/B ß-d-pyranoglucoside (1), 1-ß-d-glucopyranosyloxy-3,5-dimethoxy-4-hydroxybenzene (9), (-)-gallocatechin (10), schweinfurthinol 9-O-ß-d-pyranoglucoside (11), 1-O-(3-methyl)-butenoyl-myo-inositol (12), leonuriside (14), (+)-catechin (19), methyl galloate (20), (-)-catechin (23), and condensed tannins (5 and 18). Of these 11, novel 4 compounds (1, 11, 12, and 14) were found as new α-glucosidase inhibitors. Notably, in vitro results indicated that compounds 1, 5, 10⁻12, 18, and 19 showed potent activity (IC50 = 0.076-31 µg/mL), and their activities were at a higher level than that of acarbose, a commercial inhibitor (IC50 = 1345 µg/mL). In animal tests, the major inhibitor, condensed tannin (18), demonstrated significant reduction of plasma glucose in mice with no symptoms of diarrhea at the dose of 100 mg/kg bw. The results suggest that Euonymus laxiflorus Champ. is a rich source of bioactive compounds for development as health food or drugs with potent hypoglycemic effect. The results of this study also enriched the current novel biological activities of constituents from Euonymus laxiflorus species.

Bioactivity-Guided Purification of Novel Herbal Antioxidant and Anti-NO Compounds from Euonymus laxiflorus Champ.

Euonymus laxiflorus Champ., a medicinal herb collected in Vietnam, has been reported to show several potent bioactivities, including anti-NO, enzyme inhibition, hypoglycemic and antidiabetic effects. Recently, the antioxidant activity of Euonymus laxiflorus Champ. trunk bark (ELCTB) has also been reported. However, the active antioxidant and anti-NO constituents existing in ELCTB have not been reported in the literature. The objective of this study was to purify the active antioxidants from ELCTB and investigate the anti-NO effect of the major constituents. Twenty-two phenolics isolated from ELCTB, including 12 compounds newly isolated in this study (1⁻12) and 10 constituents obtained from our previous work, were evaluated for their antioxidant activity. Of these, 12 compounds (4⁻6, 9, 13⁻15, 18⁻22) showed a potent antioxidant capacity (FRS50 = 7.8⁻58.11 µg/mL), in comparison to α-tocopherol (FRS50 = 23 µg/mL). In the anti-NO activity tests, Walterolactone A (1a) and B (1b) ß-d-glucopyranoside (13) demonstrated the most effective and comparable activity to that of quercetin with max inhibition and IC50 values of 100%, 1.3 µg/mL, and 100%, 1.21 µg/mL, respectively. The crude extract and its major compounds showed no cytotoxicity on normal cells. Notably, three constituents (9, 11, and 12) were identified as new compounds, another three constituents, including 1, 7, and 8, were found to be new natural products, constituents 9 and 13 were determined to be new antioxidants, and compound 13 was reported to have novel potent anti-NO activity for the first time. The results of this study contribute to the enrichment of new natural products and compounds, as well as the novel biological activity of constituents isolated from Euonymus laxiflorus Champ. The current study also indicates ELCTB as a rich natural source of active phenolics. It is suggested that ELCTB could be developed as a health food with promising antioxidant and anti-NO effects, as well as other beneficial biological activities.

Chemical constituents from twigs of Euonymus alatus.

To investigate the chemical compounds from the twigs of Euonymus alatus, nine compounds were isolated and identified as(+)-delta(2,11)-enaminousnic acid(1), 11-keto-beta-boswellic acid(2), acetyl 11-keto-beta-boswellic acid(3), camaldulenic acid(4), betulinic acid(5), 6beta-hydroxy-stigmast-4-en-3-one(6), 5-hydroxy-6,7-dimethoxyflavone(7), ethyl 2,4-dihydroxy-6-methylbenzoate(8), 4,4'-dimethoxy-1,1'-biphenyl(9). Their structures were elucidated by extensive spectroscopic analysis. Among them, compound 1 was a new natural product. Compounds 2-4 and 7-9 were obtained from the Euonymus genus for the first time. In vitro study showed that compounds 2 and 3 showed significant anti-tumor activities to BEL-7402 and HCT-8 at the concentration of 10 mg x L(-1). The inhibition rate of compound 2 was 61.78% and 68.29%, whereas the inhibition rate of compound 3 had reached to 70.91% and 84.07%.

Dihydroagarofuranoid Sesquiterpenes as Acetylcholinesterase Inhibitors from Celastraceae Plants: Maytenus disticha and Euonymus japonicus.

Natural cholinesterase inhibitors have been found in many biological sources. Nine compounds with agarofuran (epoxyeudesmane) skeletons were isolated from seeds and aerial parts of Maytenus disticha and Euonymus japonicus. The identification and structural elucidation of compounds were based on spectroscopic data analyses. All compounds had inhibitory acetylcholinesterase (AChE) activity. These natural compounds, which possessed mixed or uncompetitive mechanisms of inhibitory activity against AChE, may be considered as models for the design and development of new naturally occurring drugs for management strategies for neurodegenerative diseases. This is the first report of these chemical structures for seeds of M. disticha.

[Research on quality standards of Euonymus fortunei].

To establish quality standards of Euonymus fortunei, and supply scientific evidence for the quality control of Euonymus fortunei. Empirical and microscopic identification methods were adopted to observe morphological and histological characters. The contents of water, total ash, acid-insoluble ash and alcohol-soluble extractive were analysed according to the methods of Chinese Pharmaco- poeia (2010). Dulcitol and reference herbs were used to identify materia medica of Euonymus fortunei by TLC method. The total flavonol glycosides contents were analysed by HPLC method, using quercetin and kaempferol as reference substances. Quercetin and kaempferol were separated on a C18 column (4.6 mm x 250 mm, 5 µm) with methanol-0.1% formic acid(51:49) as the mobile phase and detected at 366 nm. The flavonoid aglycones content was then multiplied by a conversion coefficient, and the result was the total flavonol glycosides content. The macroscopical identification, microscopic features and TLC methods were proper. The average contents of water, total ash, acid-insoluble ash, alcohol-soluble extractive and total flavonol glycosides were 8.76%, 6.48%, 0.31%, 17.48% and 0.211% , respectively. The quality standards established on the basis of the research results were suitable for the quality evaluation of Euonymus fortunei.

Bioassay-guided Isolation of Antiproliferative Triterpenoids from Euonymus alatus Twigs.

Euonymus alatus (Celastraceae) has been used as an anticancer agent in Korean traditional medicine. However, the potential bioactive contributors to the anticancer effects have not been thoroughly studied. Our screening test revealed that the MeOH extract of E. alatus twigs exhibited significant cytotoxicity against A549, SK-OV-3, and SK-MEL-2 cell lines. A bioassay-guided separation of the MeOH extract of E. alatus twigs resulted in the isolation and identification of 14 triterpenes as main phytochemicals. The structures of the compounds were elucidated on the basis of spectroscopic evidence as lupeol (1), betulin (2), 3ß,28,30-lup-20(29)-ene triol (3), lupenone (4), betulone (5), 28,30-dihydroxy-3-oxolup-20(29)-ene (6), messagenin (7), glut-5-en-3ß-ol (8), maslinic acid (9), hederagenin (10), 3-oxo-11α-methoxyolean-12-ene (11), 3ß-hydroxy-1-oxo-olean-12-en-28-oic acid (12), ursolic acid (13), and 2a-hydroxy- ursolic acid (14). Of these compounds, 3, 6-8, and 10-14 were isolated for the first time from this plant. All isolated triterpenoids had consistent antiproliferative activities against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines. Compounds 2, 5, and 7 showed significant cytotoxicity against all four cell lines tested, with IC50 values of 3.26-8.61 µM.

Chemical Constituents of Euonymus glabra.

One new phenolic compound (1) and one new flavan (2), together with eight known compounds (3-10) were isolated from the stems and twigs of Euonymus glabra Roxb. Their structures were elucidated mainly on the basis of 1D and 2D spectroscopic methods and circular dichroism analysis. In addition, compounds 1-10 were tested for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Compounds 1-5 and 7 exhibited moderate inhibitory activities with IC50 values ranged from 5.1 to 11.9 µM.

The methanol extract of Euonymus laxiflorus, Rubia lanceolata and Gardenia jasminoides inhibits xanthine oxidase and reduce serum uric acid level in rats.

Chinese herbal medicinal plants, Euonymus laxiflorus (EL), Rubia lanceolata (RL) and Gardenia jasminoides (GJ), have been used wildly to treat arthritis and gout in Taiwan for decades. To understand the beneficial effects of these three plants, their xanthine oxidase (XO) inhibitory activity in vitro and hypouricaemic activity in vivo were investigated. Our results suggested that methanol extracts were better than water extracts for inhibition of XO activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, except the water extract of GJ, which exhibited the strongest radical scavenging effect. In animal study, the serum urate level was significantly decreased after oral administration of higher dose (0.39g/kg) methanol extract of the mixture of three plants (ERG). In addition, methanol extract of ERG reduced the pain reaction time in the second phase of formalin induced pain. The results provide useful information on the pharmacological activities of these plants for the potential in treating hyperuricemia.

Lupane triterpenoids from the stems of Euonymus carnosus.

Fifteen new lupane-type triterpenoids (1-15) and 10 known triterpenoids (16-25) were isolated from the stems of Euonymus carnosus. The structures of the new compounds were elucidated on the basis of spectroscopic analyses, and the absolute configuration of compound 1 was confirmed by X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. In addition, the compounds were tested for their cytotoxic activity against five human cancer cell lines and their ability to inhibit LPS-induced nitric oxide production in the murine microglia BV2 cell line. Compound 11 exhibited moderate cytotoxicity against several human cancer cell lines, and compounds 1, 2, 4, 5, 20, and 25 showed neuritis inhibitory activity against microglial inflammation factor, with IC50 values of 7.39, 7.48, 7.80, 3.48, 2.54, and 6.09 µM, respectively.

Glycosylsphingolipids from Euonymus japonicus Thunb.

The stem bark of Euonymus japonicus Thunb. led to the isolation of three new glycosylsphingolipids (1-3), 1-O-[-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl]-(2S,3R,9E)-2-N-[(2R)-hydroxystearoyl]-octadecasphinga-9-ene (euojaposphingoside A, 1), 1-O-[ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl]-(2S,3R,4R,11E)-2-N-[(2R)-hydroxydocasanoyl]-octadecasphinga-11-ene (euojaposphingoside B, 2), 1-O-[ß-D-glucopyranosyl]-2'-O-[ß-D-glucopyranosyl]-(2S,3R,4R,11E)-2-N-[(2R)-hydroxytetracosanoyl]-octadecasphinga-11-ene (euojaposphingoside C, 3) along with three known glycosylsphingolipids (4-6), 1-O-[ß-D-glucopyranosyl]-(2S,3R,9E)-3-hydroxymethyl-2-N-[(2R)-hydroxynonacosanoyl)-tridecasphinga-9-ene (4), 1-O-[ß-D-glucopyranosyl]-(2S,3R,9E,12E)-2-N-[(2R)-hydroxytetracosanoyl] octadecasphinga-9,12-diene (5), 1-O-[ß-D-glucopyranosyl]-(2S,3R,5R,9E)-2-N-[tridecanoyl] nonacosasphinga-9-ene (6), lupeol (7), stigmasterol (8), sitosterol (ß and α) (9,10) and ß-carotene (11). The structure of all the compounds was achieved by spectroscopic and chemical data analysis. The antiplasmodial, antileismanial and cytotoxic activity of all compounds was tested.

Phenolic constituents from the twigs of Euonymus alatus and their cytotoxic and anti-inflammatory activity.

A bioassay-guided fractionation and chemical investigation of the MeOH extract of the twigs of Euonymus alatus resulted in the isolation and identification of five new phenolic compounds, named alatusols A-E (1-5), together with six known compounds (6-11). The structures of these new compounds were elucidated through spectral analysis, including extensive 2D-NMR data, and their absolute configurations were determined by the modified Mosher's method. Compounds 1-3 and 7-9 showed consistent cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC50 values of 15.20-29.81 µM. In addition, compounds 5 and 7 inhibited nitric oxide production in lipopolysaccharide-activated BV-2 cells with IC50 values of 22.77 and 32.52 µM, respectively.

A new flavan-3-ol lactone and other constituents from Euonymus alatus with inhibitory activities on α-glucosidase and differentiation of 3T3-L1 cells.

Bioassay-guided fractionation, based on inhibition of α-glucosidase, of Euonymus alatus led to the isolation of a new compound, catechin lactone A (7), and seven known compounds (1-6 and 8). Their structures were established on the basis of extensive 1D- and 2D-NMR experiments. The absolute configurations of compound 7 have been determined using vibrational circular dichroism spectroscopy. All these compounds were evaluated for their inhibition activities on α-glucosidase and differentiation of 3T3-L1 cells. Compounds 1, 3-5, 7 and 8 showed potent yeast α-glucosidase inhibition with IC50 values of 119.1, 39.6, 31.6, 23.0, 71.8 and 102.5 µM, respectively; compounds 3-5, 7 and 8 can remarkably inhibit the differentiation of 3T3-L1 pre-adipocytes. This is the first report about α-glucosidase and 3T3-L1 inhibitory activities of compounds 3, 7 and 8.

Euonymus alatus in the treatment of diabetic nephropathy in rats.

Diabetic nephropathy is a leading cause of chronic renal failure. Recently, Euonymus alatus showed therapeutic potential in the treatment of diabetes and its chronic complications. In this study, effects of Euonymus alatus and its mechanism in the treatment of diabetic nephropathy were investigated. Diabetic nephropathy was induced in Sprague-Dawley rats by uninephrectomy plus streptozotocin (STZ) administration. Euonymus alatus and irbesartan, as a positive control, were lavaged to these rats for 12 weeks. Our data showed that Euonymus alatus was efficient in lowering HbA1c, improving blood lipids, decreasing 24 h urine protein and protecting kidney function. Pathological studies found kidney damage, including extracellular matrix expansion and glomerulosclerosis, were improved by Euonymus alatus treatment. Further investigation found that the herb had a role in downregulating the expression of transform growth factor ß(1). In conclusion, Euonymus alatus has a protective role in diabetic nephropathy, which may be related to its downregulation of transform growth factor ß(1) expression.

Two new neolignans from the stems of Euonymus oblongifolius.

Two new neolignans, (+)-(7R,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'- oxyneoligna-7,9-diol-7'-aldehyde (1) and (-)-(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8', 9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde (2), were isolated from the stems of Euonymus oblongifolius. Their chemical structures were determined according to HR-ESI-MS, CD, 1D and 2D NMR spectroscopic analyses.