Spiraea prunifolia leaves extract inhibits adipogenesis and lipogenesis by promoting ß-oxidation in high fat diet-induced obese mice.

Spiraea prunifolia has been used in Korean traditional medicine to treat malaria, fever, and emetic conditions. Previous investigation reported that several parts of Spiraea prunifolia show various functional effects. However, the effect of Spiraea prunifolia leaves extract (SPE) on anti-obesity remains unclear. Therefore, we used a high-fat diet (HFD)-induced obese mouse model in this study to investigate the effects of SPE on adipogenesis, lipogenesis, and ß-oxidation. Oral administration of SPE in HFD-induced obese mice considerably reduced body weight, serum levels such as total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, adipose tissue weight, and adipocyte cell size. Moreover, SPE significantly decreased protein expression levels of adipogenesis and lipogenesis related genes such as CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte protein 2, acetyl-CoA carboxylase, and fatty acid synthase in epididymal adipose tissues. SPE treatment induced the protein expression of carnitine palmitoyl transferase-1, which might have promoted phosphorylated AMP-activated protein kinase-medicated ß-oxidation. The present study reveals an anti-adipogenic, anti-lipogenic, ß-oxidation effects of SPE in vivo and represents AMP-activated protein kinase signaling as targets for SPE.

Improvement of Obesity and Dyslipidemic Activity of Amomum tsao-ko in C57BL/6 Mice Fed a High-Carbohydrate Diet.

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.

Effects of anti-wrinkle and skin-whitening fermented black ginseng on human subjects and underlying mechanism of action.

The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks FBG cream significantly reduced appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.

A novel role for α-viniferin in suppressing angiogenesis by blocking the VEGFR-2/p70S6K signaling pathway.

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.

Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Outcomes after endoscopic ultrasound-guided ethanol-lipiodol ablation of small pancreatic neuroendocrine tumors.

BACKGROUND AND AIM: Little is known about the standard care of small (<2 cm in diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study was to determine the clinical outcomes of small PNET after endoscopic ultrasound (EUS)-guided ethanol-lipiodol ablation (EUS-ELA). METHODS: In this prospective cohort study, consecutive patients who underwent EUS-ELA for PNET were enrolled and were followed for ≥3 years. Treatment efficacy was the primary outcome measure. RESULTS: In total, 33 patients who had 40 pathologically confirmed PNET (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS-ELA sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6 sessions per tumor), which included 40 initial sessions and 23 repeated sessions owing to incomplete ablation. Median actual volume of ethanol-lipiodol mixture injected per session was 1.1 mL (IQR 0.8-1.9 mL). Complete ablation was achieved in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%) sessions of EUS-ELA. Lipiodol retention within tumor had better treatment outcomes (P = 0.004). Rate of procedure-related adverse events was 3.2%. No malignancy or lymph node metastasis was discovered during a median follow up of 42 months (IQR 39-46 months). CONCLUSIONS: We found that EUS-ELA was a safe and effective alternative option in the management of PNET <2.0 cm in diameter; 60% of patients achieved complete ablation. Lipiodol retention within tumor may be a useful early predictor of treatment effectiveness. Trial registered at ClinicalTrials.gov (NCT 01902238).

Trigonostemon reidioides modulates endothelial cell proliferation, migration and tube formation via downregulation of the Akt signaling pathway.

Trigonostemon reidi`oides (TR) is used as a Thai traditional medicine for the treatment of drug addiction, asthma, food poisoning, constipation and snake bites. The present study investigated the effects and molecular mechanisms of the ethanolic extract of TR (ETR) on mitogen-induced human umbilical vein endothelial cells (HUVECs) responses, proliferation, adhesion, migration and tube formation. ETR treatment inhibited mitogen-induced HUVEC proliferation by downregulation of cell cycle-associated proteins, including cyclins and cyclin-dependent kinases, which induced retinoblastoma protein hypophosphorylation. The present study also demonstrated that ETR treatment suppressed mitogen-induced HUVEC adhesion, migration, invasion and tube formation, and that these anti-angiogenic activities were mediated by inactivation of mitogen-induced Akt and matrix metalloproteinase (MMP)-2, but not of extracellular signal-regulated kinase, p70 ribosomal S6 kinase or MMP-9. Collectively, the results of the present study suggested pharmacological functions and molecular mechanisms of ETR in regulating endothelial cell fates, and supported further evaluation and development of ETR as a potential therapeutic agent for the treatment and prevention of angiogenesis-associated diseases, including cancer.

Dehydrocorydaline promotes myogenic differentiation via p38 MAPK activation.

Muscle regeneration is a coordinated process that involves proliferation and differentiation of muscle progenitor cells. Activation of MyoD is a key event in myogenic differentiation, which is regulated by p38 mitogen­activated protein kinases (MAPK). In a screen of natural compounds for the enhancement of MyoD activity, dehydrocorydaline (DHC) from the Corydalis tuber was identified. Treatment of C2C12 myoblasts with DHC increased the expression levels of muscle­specific proteins, including MyoD, myogenin and myosin heavy chain. In addition, C2C12 myoblasts exhibited enhanced multinucleated myotube formation without any cytotoxicity. Treatment with DHC elevated p38 MAPK activation and the interaction of MyoD with an E protein, which is likely to result in activation of MyoD and promotion of myoblast differentiation. Furthermore, defects in differentiation­induced p38 MAPK activation and myoblast differentiation induced by depletion of the promyogenic receptor protein Cdo in C2C12 myoblasts were restored by DHC treatment. In conclusion, these results indicated that DHC stimulates p38 MAPK activation, which can enhance heterodimerization of MyoD and E proteins, thus resulting in MyoD activation and myoblast differentiation. These findings suggested that DHC may be considered a potential therapeutic compound for the improvement of muscle stem cell regenerative capacity in injured muscle.

Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression.

Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. We also show that LF treatment inhibited cell invasion and tube formation in HUVECs. These anti-angiogenic activities of LF were associated with the inactivation of mitogenic signaling pathways, induction of vascular endothelial (VE)-cadherin distribution at cell-cell contacts and inhibition of matrix metalloproteinase (MMP) expression. Collectively, our findings demonstrate the pharmacological functions and molecular mechanisms of LF in regulating endothelial cell fates, and support further development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related disorders including cancer.

Anti-angiogenic effects of Siegesbeckia glabrescens are mediated by suppression of the Akt and p70S6K-dependent signaling pathways.

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we report the effects and molecular mechanism of an ethanolic extract of SG on cell proliferation, migration and tube formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. SG treatment inhibited VEGF-A-stimulated endothelial cell proliferation through downregulation of cyclin D and upregulation of cyclin-dependent kinase inhibitors such as p27Kip1 and p21WAF1/Cip1. In addition, SG inhibited VEGF­A-stimulated endothelial cell migration and tube formation. These anti-angiogenic activities of SG were mediated by inactivation of the Akt- and p70S6K-dependent signaling pathways. Collectively, our findings demonstrate the pharmacological roles and molecular mechanism of SG in regulating angiogenic responses and support further evaluation and development of SG as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Kazinol-P from Broussonetia kazinoki enhances skeletal muscle differentiation via p38MAPK and MyoD.

The activation of MyoD family transcription factors is critical for myogenic differentiation, which is fundamental to the regeneration of skeletal muscle after injury. Kazinol-P (KP) from Broussonetia kazinoki (B. kazinoki), a natural compound, has been reported to possess an anti-oxidant function. In a screen of natural compounds for agonists of the MyoD activity, we identified KP and examined its effect on myoblast differentiation. Consistently, KP enhanced the myotube formation, accompanied with upregulation of myogenic markers such as MHC, Myogenin and Troponin-T. KP treatment in C2C12 myoblasts led to strong activation of a key promyogenic kinase p38MAPK in a dose, and time-dependent manner. Furthermore, KP treatment enhanced the MyoD-mediated trans-differentiation of 10T1/2 fibroblasts into myoblasts. Taken together, KP promotes myogenic differentiation through activation of p38MAPK and MyoD transcription activities. Thus KP may be a potential therapeutic candidate to prevent fibrosis and improve muscle regeneration and repair.

Neolignan inhibitors of antigen-induced degranulation in RBL-2H3 cells from the needles of Pinus thunbergii.

The ethanolic extract of the needles of Pinus thunbergii was found to suppress antigen mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. A new neolignan glycoside, named pinusthunbergiside A (1), as well as six known neolignan glycosides (2-7) were isolated from the ethanolic extract using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, HRESI-MS, and circular dichroism (CD) data. Compounds 2-7 were found for the first time in this plant. The inhibitory effects of isolated constituents on the release of ß-hexosaminidase from RBL-2H3 cells were examined, and compounds 2, 3, 5, and 6 were found to show the inhibitory activity with IC50 values ranging between 52.3 and 75.3 µM.

Broussonetia kazinoki modulates the expression of VEGFR-2 and MMP-2 through the inhibition of ERK, Akt and p70S6K­dependent signaling pathways: Its implication in endothelial cell proliferation, migration and tubular formation.

Broussonetia kazinoki (BK) has been used as a traditional medicine to improve vision, as well as for inflammatory and infectious diseases. In the present study, we investigated the effects and molecular mechanism of the ethanolic extract of BK on cell proliferation, migration and tubular formation in vascular endothelial growth factor-A (VEGF-A)-treated human umbilical vein endothelial cells. BK treatment inhibited VEGF-A-stimulated endothelial cell proliferation through the downregulation of cell cycle-related proteins including cyclin-dependent kinases and cyclins. Moreover, BK treatment suppressed cell migration and tubular formation in response to VEGF-A. These anti-angiogenic activities of BK were associated with the inactivation of mitogenic signaling pathways including extracellular signal-regulated kinase, Akt and p70S6K, and the subsequent downregulation of VEGFR-2 and matrix metalloproteinase-2. Taken together, these findings suggest further evaluation and development of BK as a potential therapeutic agent for the treatment and prevention of angiogenesis-related diseases including cancer.

Preliminary report on a new hybrid metal stent for EUS-guided biliary drainage (with videos).

BACKGROUND: EUS-guided biliary drainage (EUS-BD) may be a feasible and useful alternative in patients with malignant biliary obstruction after failed ERCP. One of the main limitations of EUS-BD is the lack of devices specifically tailored to this technique. OBJECTIVE: To evaluate a newly developed hybrid metal stent customized for EUS-BD. DESIGN: A prospective, observational study. SETTING: A tertiary academic referral center. PATIENTS: A total of 27 consecutive patients with malignant biliary obstruction who were candidates for alternative techniques for biliary drainage because of failed ERCP were enrolled. INTERVENTIONS: EUS-BD with a newly developed hybrid metal stent. MAIN OUTCOME MEASUREMENTS: The technical and clinical success rates and adverse events, including proximal or distal stent migration and cholangitis. RESULTS: EUS-guided hepaticogastrostomy was performed in 10 patients, and EUS-guided choledochoduodenostomy was performed in 17 patients. The technical success rate of EUS-BD with the hybrid metal stent was 100% (27/27), and clinical success was achieved in 96.3% (26/27) of the cases. Adverse events developed in 5 patients (5/27, 18.5%), including a self-limited pneumoperitoneum in 3 patients, minor bleeding in 1 patient, and abdominal pain in 1 patient. During the follow-up period (median 134 days), proximal or distal stent migration was not observed. LIMITATIONS: This study was performed at a single center by a single experienced operator with a relatively small number of patients. CONCLUSION: EUS-BD with a hybrid metal stent is technically feasible and can be an effective treatment for malignant biliary obstruction after failed ERCP. Hybrid metal stents may be used safely in EUS-BD, and they can prevent stent-related adverse events.

Effect of HIFU treatment on tumor targeting efficacy of docetaxel-loaded Pluronic nanoparticles.

Numerous studies have been performed to identify the microenvironment of solid tumors, which is responsible for the insufficient delivery of anticancer drugs to tumor cells due to the poorly organized vasculature and the increased interstitial fluid pressure. As a result, the extravasation of convection-dependent agents including NPs is severely limited. Therefore, we have demonstrated the feasibility of targeting an enhancement of docetaxel-loaded Pluronic nanoparticles (NPs) using high-intensity focused ultrasound (HIFU) as an external stimulus-induced clinical system in tumor tissue. The efficient extravasation of NPs into the interior cells in tumor tissue was induced by relatively low HIFU exposure without apparent acute tissue damage. The enhanced targeting of NPs with near-infrared fluorescence dye was observed in tumor-bearing mice with various HIFU exposures. As a result, the greatest accumulation of NPs at the tumor tissue was observed at an HIFU exposure of 20 W/cm(2). However, the tumor tissue above at 20 W/cm(2) appeared to be destroyed and the tumor targetability of NPs was significantly decreased owing to thermal ablation with necrosis, resulting in the destruction of the tumor tissue and the blood vessels. In particular, a cross-sectional view of the tumor tissue verified that the NPs migrated into the middle of the tumor tissue upon HIFU exposure. The preliminary results here demonstrate that HIFU exposure through non-thermal mechanisms can aid with the extravasation of NPs into the interior cells of tumors and increase the therapeutic effect in enhanced and targeted cancer therapy.

Regulatory effects of Siegesbeckia glabrescens on non-small cell lung cancer cell proliferation and invasion.

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70(S6K) as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70(S6K). In contrast, in H1299 cells the inactivation of p38(MAPK) appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC.

Phytochemical linarin enriched in the flower of Chrysanthemum indicum inhibits proliferation of A549 human alveolar basal epithelial cells through suppression of the Akt-dependent signaling pathway.

In this study, we report the anti-proliferative effect and molecular mechanism of Chrysanthemum indicum (C. indicum) on A549 human alveolar basal epithelial cells. We also analyzed the changes in C. indicum component profiles due to modifications of predrying process, flower size, and extraction method. Among the varieties of modifications tested, high-temperature heat dry (HTD) of small flower biotype followed by the methanolic extraction resulted in the strongest anti-proliferative activity of C. indicum extract in A549 cells. High-performance liquid chromatography of C. indicum revealed that the levels of acacetin 7-O-rutinoside (linarin) are markedly increased by heat treatment, especially HTD. Finally, we showed that linarin-mediated inhibition of cell proliferation is associated with suppression of Akt activation and induction of cyclin-dependent kinase inhibitor p27(Kip1) as evidenced by cell cycle analysis and treatment with LY294002, an inhibitor of phosphatidylinositol 3-kinase/Akt pathway. Taken together, these findings suggest the need for further development and evaluation of linarin from C. indicum for the treatment and prevention of lung cancer.

The in vitro antitumor activity of Siegesbeckia glabrescens against ovarian cancer through suppression of receptor tyrosine kinase expression and the signaling pathways.

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of a variety of diseases such as allergy, inflammation, acute hepatitis and hypertension. The primary aim of this study was to determine whether the ethanol extract of SG has antitumor activity against ovarian cancer and to identify molecular mechanisms and targets involved in the regulation of cell growth and progression. We demonstrate that SG treatment inhibits proliferation, adhesion, migration and invasion of SKOV-3 human ovarian cancer cells. The anti-proliferative effect of SG on SKOV-3 cells is accompanied by reduced expression of cyclin E and enhanced expression of the cyclin-dependent kinase inhibitor p27(Kip1), leading to inhibition of pRb phosphorylation. We also show that these antitumor activities are found to be mediated through suppression of FAK, ERK, Akt and p70(S6K)-dependent signaling pathways and downregulation of receptor tyrosine kinases such as EGFR, VEGFR-2 and FGFR-1 as well as the cell adhesion molecule N-cadherin. Taken together, our findings suggest further development and evaluation of SG for the treatment of ovarian cancer.

Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma.

BACKGROUND: To determine the safety and efficacy of neoadjuvant gemcitabine/capecitabine followed by surgery for the treatment of locally advanced pancreatic adenocarcinoma (LAPC). METHODS: Patients with histologically confirmed LAPC were given 3-6 cycles of fixed-dose rate gemcitabine/capecitabine every 3 weeks. At the end of chemotherapy, patients were restaged and underwent surgery if the disease was not classified as unresectable. Our institutional criteria were used to classify respectability, which was recategorized on the basis of National Comprehensive Cancer Network (NCCN) criteria retroactively. The primary end point was rate of microscopic curative resection. RESULTS: Forty-three eligible patients (18 with borderline resectable disease and 25 with unresectable disease on the basis of NCCN criteria) were enrolled. The radiologic response rate was 18.6%. Grade three or worse adverse events were mainly hand-foot syndrome (11%), and there were no grade four adverse events. Surgery was performed in 17 patients (39.5%); pathologic curative resection (R0) was achieved in 14 patients (32.5%) among total 43 patients, and 82.3% (14/17) among the 17 resected patients. With 43-month follow-up, the median overall was 16.6 months with a median progression-free survival of 10.0 months. Median overall survival was 23.1 months in patients who underwent surgery and 13.2 months in patients who could not complete the surgery (P = .017). CONCLUSION: A subset of patients with borderline or unresectable pancreatic cancer could be performed curative tumor resection after neoadjuvant chemotherapy. Some patients might be benefit on survival from neoadjuvant chemotherapy after surgical resection.

1ß-Hydroxy-2-oxopomolic acid isolated from Agrimonia pilosa extract inhibits adipogenesis in 3T3-L1 cells.

In order to determine anti-adipogenic effect, this study investigated 1ß-hydroxy-2-oxopomolic acid (HOA) isolated from Agrimonia pilosa inhibits adipocyte differentiation and expression of adipogenic marker genes, such as peroxisome proliferator activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), glucose transporter 4 (GLUT4), adiponectin, adipocyte fatty acid-binding protein 2 (aP2), adipocyte determination and differentiation factor 1/sterol regulatory element binding protein 1c (ADD1/SREBP1c), resistin, and fatty acid synthase (Fas) in 3T3-L1 preadipocyte. We demonstrated that HOA induced a significant decrease in lipid accumulation and expression of adipogenic marker genes in a dose-dependent manner. In addition, HOA reduced the transcripitional activity of PPARγ induced by troglitazone, a potent diabetes agent; it also suppressed expression of PPARγ and C/EBPα protein levels. Our data suggest that HOA isolated from Agrimonia pilosa inhibits adipocyte differentiation through downregulation of various adipocytokines by blocking PPARγ and C/EBPα expression.