Synthesis and antihepatoma activity of guaianolide dimers derived from lavandiolide I.

Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers.

Self-Driven Droplet Motions Below their Icing Points.

Liquid fluidity is a most key prerequisite for a broad range of technologies, from energy, fluid machineries, microfluidic devices, water, and oil transportation to bio-deliveries. While from thermodynamics, the liquid fluidity gradually diminishes as temperature decreases until completely solidified below icing points. Here, self-driven droplet motions are discovered and demonstrated occurring in icing environments and accelerating with both moving distances and droplet volumes. The self-driven motions, including self-depinning and continuous wriggling, require no surface pre-preparation or energy input but are triggered by the overpressure spontaneously established during icing and then continuously accelerated by capillary pulling of frosts. Such self-driven motions are generic to a broad class of liquid types, volumes, and numbers on various micro-nanostructured surfaces and can be facilely manipulated by introducing pressure gradients spontaneously or externally. The discovery and control of self-driven motions below icing points can greatly broaden liquid-related applications in icing environments.

Hantzsch Ester as Efficient and Economical NAD(P)H Mimic for In Vitro Bioredox Reactions.

Biocatalysis has emerged as a valuable and reliable tool for industrial and academic societies, particularly in fields related to bioredox reactions. The cost of cofactors, especially those needed to be replenished at stoichiometric amounts or more, is the chief economic concern for bioredox reactions. In this study, a readily accessible, inexpensive, and bench-stable Hantzsch ester is verified as the viable and efficient NAD(P)H mimic by four enzymatic redox transformations, including two non-heme diiron N-oxygenases and two flavin-dependent reductases. This finding provides the potential to significantly reduce the costs of NAD(P)H-relying bioredox reactions.

Functional Materials for Water Restoration: A "Fish Cage" for Efficient Capture of Pb(II) Ions.

In this work, a "fish cage" material for trapping Pb(II) ions has been successfully obtained, which is a novel clathrate functionalized metal-oganic framework (Cage-MOF) by introducing free adsorption sites (SO42-). The three-dimensional (3D) cage structure of Cage-MOF gives it a larger contact area and can capture "swimming fish" (Pb(II)) like a "fishing cage" in a water solution. This is the first high-efficiency adsorption material obtained by introducing free coordination groups. Cage-MOF not only has excellent water stability but also improves the selectivity and affinity for Pb(II) ions in water because of the presence of sulfate adsorption sites, and its adsorption capacity is as high as 806 mg/g. This work shows a novel and effective idea for the synthesis of water restoration materials.

Artemannuols A-C, novel sesquiterpenoid-flavonol hybrids with antihepatoma activity from Artemisia annua.

Artemisia annua, also known as "Qinghao" in Chinese, is a famous traditional Chinese medicine and has been used for the treatment of malaria and various tumors. In this study, three novel sesquiterpenoid-flavonol hybrids, artemannuols A-C (1-3), were isolated and elucidated by extensive spectral data and ECD calculations. Structurally, artemannuols A-C (1-3) are the first examples of sesquiterpenoid-flavonol hybrids fused by an ether bond, among which artemannuols A and B (1 and 2) are composed of bisabolane-type sesquiterpenoid and flavonol moieties, and artemannuol C (3) is composed of humulane-type sesquiterpenoid and flavonol moieties. The antihepatoma assay suggested that compounds 1-3 showed inhibitory effects against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values in the range of 32.7 to 70.4 µM.

Artemongolides A-F, undescribed sesquiterpenoid dimers from Artemisia mongolica and their antihepatic fibrosis activities.

Artemongolides A-E (1-5), an unusual class of diseco-guaianolides featuring a rare fused 7-methylbicyclo[2.2.1]-2-ene-7-heptanol ring system, and artemongolide F (6), the first example of [4 + 2] Diels-Alder type adducts presumably incorporating a chain farnesane sesquiterpene and a guaianolide diene, were isolated from the whole plant of Artemisia mongolica. Their structures were elucidated based on the spectroscopic analyses of UV, IR, MS, and 1D and 2D NMR spectra. The absolute configurations of artemongolides A (1) and F (6) were determined by single-crystal X-ray crystallography, and those of artemongolides B-E (2-5) were established by ECD calculations. Cytotoxicity evaluation suggested that compound 1 exhibited activity against HSC-LX2 cells with an IC50 value of 165.0 µM, equivalent to that of the positive control silybin (IC50, 146.4 µM). Preliminary mechanism studies revealed that compound 1 could inhibit the deposition of human collagen type I (Col I), human hyaluronic acid (HA), and human laminin (HL) with IC50 values of 123.8, 160.4, and 139.20 µM.

Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents.

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.

Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents.

Genome-wide characterization and expression analysis of SAUR gene family in Melon (Cucumis melo L.).

MAIN CONCLUSION: We identified 66 melon SAUR genes by bioinformatic analyses. CmSAUR19, 38, 58, 62 genes are specifically expressed in different stages of fruit growth, suggesting their participation in regulating fruit development. Auxin plays a crucial role in plant growth by regulating the multiple auxin response genes. However, in melon (Cucumis melo L.), the functions of the auxin early response gene family SAUR (Small auxin up RNA) genes in fruit development are still poorly understood. Through genome-wide characterization of CmSAUR family in melon, we identified a total of 66 CmSAUR genes. The open reading frames of the CmSAUR genes ranged from 234 to 525 bp, containing only one exon and lacking introns. Chromosomal position and phylogenetic tree analyses found that the two gene clusters in the melon chromosome are highly homologous in the Cucurbitaceae plants. Among the four conserved motifs in CmSAUR proteins, motif 1, motif 2, and motif 3 located in most of the family protein sequences, and motif 4 showed a close correlation with the two gene clusters. The CmSAUR28 and CmSAUR58 genes have auxin response elements located in the promoters, suggesting they may be involved in the auxin signaling pathway to regulate fruit development. Through transcriptomic profiling in the four developmental stages of fruit and different lateral organs, we selected 16 differentially-expressed SAUR genes for performing further expression analyses. qRT-PCR results showed that five SAUR genes are specifically expressed in flower organs and ovaries. CmSAUR19 and CmSAUR58 were significantly accumulated in the early developmental stage of the fruit. CmSAUR38 and CmAUR62 showed high expression in the climacteric and post-climacteric stages, suggesting their specific role in controlling fruit ripening. This work provides a foundation for further exploring the function of the SAUR gene in fruit development.

Beneficial effects of metformin supplementation in hypothalamic paraventricular nucleus and arcuate nucleus of type 2 diabetic rats.

Background Oxidative stress and inflammation play important roles in the development of diabetes. Metformin (MET) is considered as the first-line therapy for patients with type 2 diabetes (T2D). Hypothalamic paraventricular nucleus (PVN) and hypothalamic arcuate nucleus (ARC) are vital in obesity and diabetes. However, there have been few studies on the effects of MET on inflammatory reaction and oxidative stress in the PVN and ARC of T2D diabetic rats. Methods Male Sprague-Dawley (SD) rats were fed with high-fat diet (HFD), and intraperitoneally injected with low-dose streptozotocin (STZ, 30 mg/kg) at 6th week to induce T2D diabetes. After injection of STZ, they were fed with HFD continually. Starting from the 8th week of HFD feeding, T2D rats received intragastrical administration of MET (150 mg/kg/day) in addition to the HFD for another 8 weeks. At the end of the 15th week, the rats were anaesthetized to record the sympathetic nerve activity and collect blood and tissue samples. Results In comparison with control rats, T2D diabetic rats had higher levels of pro-inflammatory cytokines (PICs) and excessive oxidative stress in the PVN and ARC, accompanied with more activated astrocytes. The renal sympathetic nerve activity (RSNA) and the plasma norepinephrine (NE) increased in T2D diabetic rats. The expression of tyrosine hydroxylase (TH) increased and the expression of 67-kDa isoform of glutamate decarboxylase (GAD67) decreased in T2D diabetic rats. Supplementation of MET decreased blood glucose, suppressed RSNA, decreased PICs (TNF-α, IL-1ß and IL-6) in PVN and ARC, attenuated oxidative stress and activation of astrocytes in ARC and PVN of T2D diabetic rats, as well as restored the balance of neurotransmitter synthetase. The number of Fra-LI (chronic neuronal excitation marker) positive neurons in the ARC and PVN of T2D diabetic rats increased. Chronic supplementation of MET also decreased the number of Fra-LI positive neurons in the ARC and PVN of T2D diabetic rats. Conclusion These findings suggest that the PVN and ARC participate in the beneficial effects of MET in T2D diabetic rats, which is possibly mediated via down-regulating of inflammatory molecules, attenuating oxidative stress and restoring the balance of neurotransmitter synthetase by MET in the PVN and ARC.

Anisotropic Hemiwicking Behavior on Laser Structured Prismatic Microgrooves.

The wicking phenomenon, including wicking and hemiwicking, has attracted increasing attention for its critical importance to a wide range of engineering applications, such as thermal management, water harvesting, fuel cells, microfluidics, and biosciences. There exists a more urgent demand for anisotropic wicking behaviors since an increasing number of advanced applications are significantly complex. For example, special-shaped vapor chambers and heating atomizers in some electronic cigarettes need liquid replenishing with various velocities in different directions. Here, we report two-dimensional anisotropic hemiwicking behaviors with elliptical shapes on laser structured prismatic microgrooves. The prismatic microgrooves were fabricated via one-step femtosecond laser direct writing, and the anisotropic hemiwicking behaviors were observed when utilizing glycerol, glycol, and water as the test liquid. Specifically, the ratios of horizontal wicking distance in directions along short and long axes were tan 0°, tan 15°, tan 30°, and tan 45° for samples with cross-angles of 0°, 30°, 60°, and 90°, respectively. The vertical water wicking front displayed corresponding angles under the guidance of laser structured prismatic microgrooves. Theoretical analysis shows that the wicking distance is mainly dependent on the cross-angle θ and surface roughness, in which the wicking distance is proportional to cos(θ/2). Driven by the capillary pressure forming in the narrow microgrooves, the liquid initially filled the valleys of microgrooves and then surrounded and covered the prismatic ridges with laser-induced nanoparticles. The abundant nanoparticles increased the surface roughness, leading to the enhancement of wicking performance, which was further evidenced by the larger wicking speed of the sample with more nanoparticles. The mechanism of anisotropic hemiwicking behaviors revealed in this work paves the way for wicking control, and the proposed prismatic microgrooved surfaces with two-dimensional anisotropic hemiwicking performance and superhydrophilicity could serve in a broad range of applications, especially for the advanced thermal management with specific heat load configurations.

Design, synthesis and anti-breast cancer evaluation of biaryl pyridine analogues as potent RSK inhibitors.

In order to discover and develop the new RSK kinase inhibitor, 50 pyridyl biaryl derivatives were designed and synthesized with LJH685 as the lead compound and their anti-tumor ability was tested. The results showed that the ability of 7d compound to inhibit the phosphorylation of YB-1 was comparable to that of LJH685. Among them, after preliminary screening, compound 7d showed good activity in inhibiting cell proliferation. Therefore, we took 7d as an example and performed molecular docking analysis on it. Judging from the overlapping combination diagram with LJH685, the results have verified that compound 7d has a similar skeleton to LJH685 and has a similar docking effect with RSK. Therefore, compound 7d is in line with the RSK inhibitor we designed and could be developed to a promising anti-tumor drug in the future.

Artemzhongdianolides A1-A21, antihepatic fibrosis guaiane-type sesquiterpenoid dimers from Artemisia zhongdianensis.

In the search for new antihepatic fibrosis candidates, it was observed that the EtOH extract of Artemisia zhongdianensis and EtOAc fraction had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with the inhibitory ratios of 85.7 % and 83.9 % at 400 µg/mL. 21 new guaianolide dimers, artemzhongdianolides A1 - A21 (1-21) were isolated from the active fractions under the guidance of bioassay, and elucidated by spectral analyses (HRESIMS, 1D and 2D NMR, IR, ECD). The absolute stereochemistry of compounds 1, 13, and 14 was determined by single-crystal X-ray diffraction analyses. Cytotoxicity evaluation suggested that nine compounds exhibited activity against HSC-LX2 with IC50 values ranging from 14.0 to 95.2 µM. Of them, compounds 2, 6, and 13 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 22.1, 24.3 and 14.0 µM, which were 6 to 10 times more active than the positive drug silybin (IC50, 148.6 µM). Preliminary mechanism study revealed that compounds 2, 6, and 13 could markedly inhibited the deposition of human collagen type Ⅰ (Col Ⅰ), human hyaluronic acid (HA), and human laminin (HL) with IC50 values of 37.9, 54.8, and 28.0 µM (Col Ⅰ), 29.5, 25.3, and 42.9 µM (HL), 31.2, 94.6, and 12.4 µM (HA), which were 1.5 to 13-fold more potent than silybin.

New diarylheptanoid dimers as GLP-1 secretagogues and multiple-enzyme inhibitors from Alpinia katsumadai.

Ten new diarylheptanoid dimers, katsumadainols C1 - C10 (1-10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1-5 and 7-10 significantly stimulated GLP-1 secretion by 267.5-433.1% (25.0 µM) and 117.8-348.2% (12.5 µM). Compounds 1-4 exhibited significant inhibition on GPa with IC50 values of 18.0-31.3 µM; compounds 1-5 showed obvious inhibition on α-glucosidase with IC50 values of 6.9-18.2 µM; compounds 1-5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 µM. This investigation first disclosed compounds 1-4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.

Case Report: Bilateral Corneal Ectasia Developed during Pregnancy after Small-incision Lenticule Extraction.

SIGNIFICANCE: This case highlights that hormonal changes during pregnancy could affect the biomechanical stability of the cornea and lead to corneal ectasia during pregnancy after corneal refractive surgery. PURPOSE: We report an unusual case of bilateral corneal ectasia after small-incision lenticule extraction that developed during pregnancy. CASE REPORT: A 27-year-old woman experienced post-small-incision lenticule extraction corneal ectasia. Her pre-operative corneal topography was normal, with a minimum central corneal thickness of 538 µm in the right eye and 530 µm in the left eye. The manifest refraction was -7.75 -0.25 × 180 and -7.50 -0.75 × 10, and the lenticule thickness was 140 and 139 µm in the right and left eyes, respectively. After 11 months, in her first trimester, the patient began to experience gradually deteriorating blurred vision. Two years post-operatively, corneal ectasia was diagnosed based on topographic data. The automatic optometer examination was -7.25 -2.50 × 42 in the right eye and -11.00 -5.00 × 140 in the left eye. Later, the patient underwent corneal collagen cross-linking to control further progression and was recommended to wear rigid gas-permeable contact lenses. CONCLUSIONS: Surgeons should be alert for cornea ectasia after refractive surgery in pregnant patients, as hormonal changes during pregnancy may affect corneal biomechanical stability.

Complete Thoracoscopic Resection of Left Ventricular Myxoma - A Case Report.

Cardiac myxoma is a common cardiac tumor. Most are found in the left cardiac system, of which 75% of myxomas are located in the left atrium [Pinede 2001], and the origin of the left ventricle is relatively rare. Surgical resection is the most effective method for the treatment of myxoma, but because of the complex anatomy of the left ventricle, most of the reported cases are performed through the traditional median thoracotomy through the ascending aorta and vena cava to establish cardiopulmonary bypass. It is rare to establish cardiopulmonary bypass through the femoral artery and femoral vein to remove left ventricular myxoma under complete video-assisted thoracoscopy. This paper reports the surgical process and perioperative echocardiographic, magnetic resonance, radiological and pathological features of a completely thoracoscopic resection of left ventricular myxoma.

Deciphering the Genetic Basis of Root and Biomass Traits in Rapeseed (Brassica napus L.) through the Integration of GWAS and RNA-Seq under Nitrogen Stress.

An excellent root system is responsible for crops with high nitrogen-use efficiency (NUE). The current study evaluated the natural variations in 13 root- and biomass-related traits under a low nitrogen (LN) treatment in a rapeseed association panel. The studied traits exhibited significant phenotypic differences with heritabilities ranging from 0.53 to 0.66, and most of the traits showed significant correlations with each other. The genome-wide association study (GWAS) found 51 significant and 30 suggestive trait-SNP associations that integrated into 14 valid quantitative trait loci (QTL) clusters and explained 5.7-21.2% phenotypic variance. In addition, RNA sequencing was performed at two time points to examine the differential expression of genes (DEGs) between high and low NUE lines. In total, 245, 540, and 399 DEGs were identified as LN stress-specific, high nitrogen (HN) condition-specific, and HNLN common DEGs, respectively. An integrated analysis of GWAS, weighted gene co-expression network, and DEGs revealed 16 genes involved in rapeseed root development under LN stress. Previous studies have reported that the homologs of seven out of sixteen potential genes control root growth and NUE. These findings revealed the genetic basis underlying nitrogen stress and provided worthwhile SNPs/genes information for the genetic improvement of NUE in rapeseed.

Extraction, Characterization, and Platelet Inhibitory Effects of Two Polysaccharides from the Cs-4 Fungus.

Cardiovascular diseases are associated with platelet hyperactivity, and downregulating platelet activation is one of the promising antithrombotic strategies. This study newly extracted two polysaccharides (purified exopolysaccharides, EPSp and purified intercellular exopolysaccharides, IPSp) from Cordyceps sinensis Cs-4 mycelial fermentation powder, and investigated the effects of the two polysaccharides and their gut bacterial metabolites on platelet functions and thrombus formation. EPSp and IPSp are majorly composed of galactose, mannose, glucose, and arabinose. Both EPSp and IPSp mainly contain 4-Galp and 4-Glcp glycosidic linkages. EPSp and IPSp significantly inhibited human platelet activation and aggregation with a dose-dependent manner, and attenuated thrombus formation in mice without increasing bleeding risk. Furthermore, the EPSp and IPSp after fecal fermentation showed enhanced platelet inhibitory effects. The results have demonstrated the potential value of Cs-4 polysaccharides as novel protective ingredients for cardiovascular diseases.

Design and synthesis of ludartin derivatives as potential anticancer agents against hepatocellular carcinoma.

Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC50 values of 32.7 and 34.3 µM, respectively. In this study, 34 ludartin derivatives were designed, synthesized and evaluated for their cytotoxic activities against HepG2 and Huh7 cell lines using an MTT assay in vitro. As a result, 17 compounds increased the activity against HepG2 cells, and 20 compounds enhanced the activity against Huh7 cells; 14 derivatives 2, 4-7, 9, 11, 17, 24, 28-30 and 32-33 were superior to ludartin on both HepG2 and Huh7 cells. In particular, dimeric derivative 33 as the most active compound showed 20-fold and 17-fold enhancement of cytotoxicity against HepG2 and Huh7 cells compared to that of ludartin. These results suggested that compound 33 could serve as a promising lead compound against liver cancer. Graphical abstract.

Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3ß,12ß,25-triol derivatives as α-glucosidase and PTP1B inhibitors.

The dammarane triterpenoid (20S,24R)-epoxy-dammarane-3ß,12ß,25-triol obtained from Cyclocarya paliurus in our previous study showed inhibitory activity on α-glucosidase in vitro with an inhibitory ratio of 32.2% at the concentration of 200 µM. In order to reveal the structure-activity relationships (SARs) and get more active compounds, 42 derivatives of (20S,24R)-epoxy-dammarane-3ß,12ß,25-triol were synthesized by chemical modification on the hydroxyls (C-3 and C-12), rings A and E, and assayed for their α-glucosidase and PTP1B inhibitory activities. Two compounds (8, 26) increased activity against α-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both α-glucosidase and PTP1B as dual-target inhibitors with IC50 values of 489.8, 467.7 µM (α-glucosidase) and 319.7, 269.1 µM (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on α-glucosidase and a noncompetitive-type inhibitor on PTP1B based on enzyme kinetic study. Furthermore, compound 42 could selectively inhibited PTP1B as a mix-type inhibitor with IC50 value of 134.9 µM, which was 2.5-fold higher than the positive control, suramin sodium (IC50 339.0 µM), but not inhibit α-glucosidase.