mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass.
Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM.
SourceDepartment of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.

Abstract
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in
Nat Rev Drug Discov. 2011;10(8):576.

Sänker blodsockret hos diabetesråttor

Fitoterapia. 2011 Oct 24. [Epub ahead of print]
Anti-diabetic potential of ursolic acid stearoyl glucoside: A new triterpenic gycosidic ester from Lantana camara.
Kazmi I, Rahman M, Afzal M, Gupta G, Saleem S, Afzal O, Shaharyar MA, Nautiyal U, Ahmed S, Anwar F.
Source

Siddhartha Institute of Pharmacy, Uttarakhand, India.
Abstract

A new stearoyl glucoside of ursolic acid, urs-12-en-3β-ol-28-oic acid 3β-d-glucopyranosyl-4'-octadecanoate and other compounds were isolated from the leaves of Lantana camara L. The structure of this new glycoside was elucidated and established by standard spectroscopic methods. In streptozotocin-induced diabetic rats it showed significant reduction in blood glucose level.

Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

PMID:
22051701

Motverkar kognitiva problem hos diabetikerråttor

Brain Behav Immun. 2011 Nov;25(8):1658-67. Epub 2011 Jun 25.
Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice.
Lu J, Wu DM, Zheng YL, Hu B, Cheng W, Zhang ZF, Shan Q.
Source

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province, PR China.
Abstract

Evidence suggests that obesity-induced cognitive impairments are driven by in brain inflammatory responses and inflammation-mediated brain insulin resistance. Ursolic acid (UA), a triterpenoid compound, has many important biological functions, including antioxidant and anti-inflammatory activities. Here, we evaluated the effect of UA on cognitive impairment induced by a high-fat diet (HFD), and we explored the potential mechanisms mediating this effect. Results showed that UA administration significantly improved the behavioral performance of C57/BL6J mice fed a HFD in both the step-through test and the Morris water maze task. These results were associated with the inhibition of endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory signaling and the restoration of insulin signaling and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. UA administration also increased memory-related protein expression in the hippocampus of mice given a HFD. However, the neuroprotective effects of UA were blocked by an intracerebroventricular (i.c.v.) injection of PI-103, a specific PI3K 110α inhibitor. These results suggest that UA may be a potent candidate for the prevention and treatment of cognitive deficits caused by type 2 diabetes.

Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

PMID:
21708244

PPAR-α agonist, (fettmetabolsimen)

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5876-80. Epub 2011 Aug 3.
Ursolic acid is a PPAR-α agonist that regulates hepatic lipid metabolism.
Jia Y, Bhuiyan MJ, Jun HJ, Lee JH, Hoang MH, Lee HJ, Kim N, Lee D, Hwang KY, Hwang BY, Choi DW, Lee SJ.
Source

Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
Abstract

In this study, we confirmed that ursolic acid, a plant triterpenoid, activates peroxisome proliferator-activated receptor (PPAR)-α in vitro. Surface plasmon resonance and time-resolved fluorescence resonance energy transfer analyses do not show direct binding of ursolic acid to the ligand-binding domain of PPAR-α; however, ursolic acid enhances the binding of PPAR-α to the peroxisome proliferator response element in PPAR-α-responsive genes, alters the expression of key genes in lipid metabolism, significantly reducing intracellular triglyceride and cholesterol concentrations in hepatocytes. Thus, ursolic acid is a PPAR-α agonist that regulates the expression of lipid metabolism genes, but it is not a direct ligand of PPAR-α.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
21855333

Minskar blodsockret och blodfetter samt skyddar mot bukfetma hos möss

J Med Food. 2011 Nov;14(11):1375-82. Epub 2011 May 25.
Ursolic Acid, a Pentacyclic Triterpene from Sambucus australis, Prevents Abdominal Adiposity in Mice Fed a High-Fat Diet.
Rao VS, de Melo CL, Queiroz MG, Lemos TL, Menezes DB, Melo TS, Santos FA.
Source

1 Department of Physiology and Pharmacology, Biomedical Institute of Brazilian Semiarid, Faculty of Medicine, Federal University of Ceará , Fortaleza, Ceará, Brazil .
Abstract

Abstract Currently, there is renewed interest in plant-based medicines and functional foods for the prevention and cure of obesity and its associated risk of cardiovascular disease and metabolic syndrome. In the search for potential anti-obesity compounds from natural sources, the effects of ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, was evaluated for its effects on blood glucose, lipids, and abdominal fat deposition in mice fed a high-fat diet (HFD). Adult male Swiss mice treated or not with UA (0.05%, 50 mg/L, in drinking water) were fed HFD for 15 weeks. A sibutramine (SIB)-treated group (0.05% in drinking water) was included as the positive control. Weekly body weights and food and water consumption were measured, and at the end of the study period, the levels of blood glucose and lipids, the plasma hormones insulin, ghrelin, and leptin, and the abdominal fat accumulation were analyzed. Mice treated with UA and fed HFD showed significantly (P<.05) decreased body weights, visceral adiposity, and levels of blood glucose and plasma lipids relative to their respective controls not fed UA. Also, a significant increase was observed in plasma leptin with a decrease in ghrelin, as well as of amylase and lipase activities. The SIB-treated group also manifested effects similar to those of UA except for the blood glucose level, which was not different from the HFD control. These findings suggest that UA ameliorates abdominal adiposity and decreases the levels of blood glucose and plasma lipids in mice and thus manifests an anti-obesity potential through absorptive and metabolic targets.

PMID:
21612453

Aromatasinihiberare

Eur J Med Chem. 2008 Sep;43(9):1865-77. Epub 2007 Dec 7.
Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition.
Gnoatto SC, Dassonville-Klimpt A, Da Nascimento S, Galéra P, Boumediene K, Gosmann G, Sonnet P, Moslemi S.
Source

Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre 90610-000, RS, Brazil.
Abstract

The inhibitory potency of ursolic acid extracted from Ilex paraguariensis, a plant used in South American population for a tea preparation known as maté, and its derivatives to inhibit aromatase activity was assessed and compared to a phytoestrogen apigenin and a steroidal aromatase inhibitor 4-hyroxyandrostenedione (4-OHA). Among all compounds tested only ursolic acid 1 showed an efficient and dose-dependent aromatase inhibition with IC50 value of 32 microM as did apigenin (IC50=10 microM), whereas IC50 value of 4-OHA was 0.8 microM. Our results show that the incorporation of a metallocene moiety into the ursolic acid derivatives decreases the aromatase inhibition. Moreover, comparison of the structure/inhibitory potency relationship of compounds indicates that the presence of cycle A and the configuration of C3-OH and C17-COOH seems to be more favourable to recognize the active site of aromatase and to block its activity.

PMID:
18192087

Fettförbrännare?

Mol Nutr Food Res. 2010 Nov;54(11):1609-17.
Ursolic acid stimulates lipolysis in primary-cultured rat adipocytes.
Li Y, Kang Z, Li S, Kong T, Liu X, Sun C.
Source

Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, PR China.
Abstract

Ursolic acid (UA) is a pentacyclic triterpenic acid with many biological functions naturally existing in many kinds of food. To investigate whether UA can accelerate lipolysis, primary-cultured rat adipocytes were treated with UA, and glycerol release in the culture medium was measured. UA stimulated lipolysis significantly. Furthermore, the lipolytic effect of UA was inhibited by the protein kinase A (PKA) specific inhibitor H89, suggesting that UA exerted its lipolytic function through the cAMP-dependent PKA pathway. Downstream targets of the PKA pathway, hormone-sensitive lipase (HSL) and perilipin A were checked, UA enhanced lipolysis by promoting the translocation of HSL from the cytosol to the lipid droplets and inhibiting the expression of perilipin A. Additionally, adipose triglyceride lipase (ATGL), a novel rate-limiting lipase in the lipolytic catabolism, was upregulated by UA. UA-induced expression of ATGL could not be blocked by H89, suggesting that ATGL upregulation is not regulated by the PKA pathway. These findings suggest that UA significantly stimulates lipolysis by translocating HSL, decreasing perilipin A expression by the PKA pathway, and up-regulating ATGL in primary cultured adipocytes. Thus, UA is a promising candidate for the treatment of obesity.

PMID:
20521271

osv..

En sak är säker och det är att jag kommer nypa en burk direkt när de kommer!
Bara en sådan sak som mindre bukfetma går man igång på direkt, måste provas..

En annan bonus är att Jacked Ursolic Acid Extreme kommer att vara 300% starkare än Patric Arnolds vilket är den starkaste Ursolic Acid produkten på marknaden idag.

Ursprungligen postat av MMSports

En sak är säker och det är att jag kommer nypa en burk direkt när de kommer!
Bara en sådan sak som mindre bukfetma går man igång på direkt, måste provas..

En annan bonus är att Jacked Ursolic Acid kommer att vara 300% starkare än Patric Arnolds vilket är den starkaste ursolic produkten på marknaden idag.

Jacked? pratar du om en egen produkt ni ska ta fram eller?

Jacked kommer nu även bli ett varumärke

Nya produkter som tex Ursolic Acid Extreme kommer lanseras under varumärket Jacked

Ursprungligen postat av Toni

Gött! Kommer denna Jacked Ursolic Acid kanske hinna finnas med i julstrumpan den 12/24?

Det kommer Jacked Ursolic Acid Extreme att göra..
Enda problemet är att det kommer först en begränsad upplaga om cirka 10dagar.
Sen kommer den större upplagan runt årsskiftet.

Förmodar att första upplagan kommer sälja slut direkt.

Ursprungligen postat av Grunewald

Men den hinner iaf läggas upp på hemsidan, så att man hinner knipa den om man är kvick i fingrarna?

Om man är med första dagen skall det inte vara ett problem hoppas jag..
Det som strular till det extra är att de kommer in samtidigt som FF 2011..och då kommer det även säljas på mässan.

Uhmmm låter kanske inget vidare men jag kommer själv nypa en direkt som sagt...(: )
Känns som en produkt som kommer passa mig perfekt på flera punkter.

gimme gimme gimme

bra mot alzheimers

J Biol Chem. 2011 Oct 7;286(40):34914-22. Epub 2011 Aug 11.
A high content drug screen identifies ursolic acid as an inhibitor of amyloid beta protein interactions with its receptor CD36.
Wilkinson K, Boyd JD, Glicksman M, Moore KJ, El Khoury J.
Source

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Abstract

A pathological hallmark of Alzheimer disease (AD) is deposition of amyloid β (Aβ) in the brain. Aβ binds to microglia via a receptor complex that includes CD36 leading to production of proinflammatory cytokines and neurotoxic reactive oxygen species and subsequent neurodegeneration. Interruption of Aβ binding to CD36 is a potential therapeutic strategy for AD. To identify pharmacologic inhibitors of Aβ binding to CD36, we developed a 384-well plate assay for binding of fluorescently labeled Aβ to Chinese hamster ovary cells stably expressing human CD36 (CHO-CD36) and screened an Food and Drug Administration-approved compound library. The assay was optimized based on the cells' tolerance to dimethyl sulfoxide, Aβ concentration, time required for Aβ binding, reproducibility, and signal-to-background ratio. Using this assay, we identified four compounds as potential inhibitors of Aβ binding to CD36. These compounds were ursolic acid, ellipticine, zoxazolamine, and homomoschatoline. Of these compounds, only ursolic acid, a naturally occurring pentacyclic triterpenoid, successfully inhibited binding of Aβ to CHO-CD36 cells in a dose-dependent manner. The ursolic acid effect reached a plateau at ~20 μm, with a maximal inhibition of 64%. Ursolic acid also blocked binding of Aβ to microglial cells and subsequent ROS production. Our data indicate that cell-based high-content screening of small molecule libraries for their ability to block binding of Aβ to its receptors is a useful tool to identify novel inhibitors of receptors involved in AD pathogenesis. Our data also suggest that ursolic acid is a potential therapeutic agent for AD via its ability to block Aβ-CD36 interactions.

PMID:
21835916

anti tumör/ anti cancer

J Biomed Biotechnol. 2011;2011:419343. Epub 2011 May 30.
Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo.
Wang X, Zhang F, Yang L, Mei Y, Long H, Zhang X, Zhang J, Qimuge-Suyila, Su X.
Source

PET-CT Center, The Affiliated Hospital of Inner Mongolia Medical College, TongDao North Street, Hohhot 010050, China.
Abstract

The aims of the study are to explore the effect of ursolic acid (UA) on the growth of gastric cancer cell line BGC-803 and hepatocellular cancer cell H22 xenograft and to understand the mechanism. UA inhibits growth of BGC-803 cells in vitro in dose-dependent and time-dependent manner. Treated with UA in vivo, tumor cells can be arrested to G0/G1 stage. The apoptotic rate was significantly increased in tumor cells treated with UA both in vitro and in vivo. DNA fragmentation was found in BGC-803 cells exposed to UA. UA activated caspase-3, -8, and -9 and down regulated expression of Bcl-2 in BGC-803 cells. The expression of caspase-3 and -8 was elevated in tumor cells from xenograft treated with UA. ¹⁸F-FLT PET-CT imaging confirmed tumor model and UA effectiveness. Our results indicated that UA inhibits growth of tumor cells both in vitro and in vivo by decreasing proliferation of cells and inducing apoptosis.

PMID:
21716649

Yao Xue Xue Bao. 2011 May;46(5):556-60.
[Synthesis and anti-tumor activity of ursolic acid derivatives].
[Article in Chinese]
Meng YQ, Liu D, Bai ZW, Cai LL, Ai HR.
Source

Department of Pharmaceutical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China. mengyanqiu@hotmail.com

Chin Med. 2011 Jul 22;6(1):27.
Anti-cancer natural products isolated from chinese medicinal herbs.
Tan W, Lu J, Huang M, Li Y, Chen M, Wu G, Gong J, Zhong Z, Xu Z, Dang Y, Guo J, Chen X, Wang Y.
Source

State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Av, Padre Toma's Pereira S,J,, Taipa, Macao SAR, China. xpchen@umac.mo.

Eur J Med Chem. 2011 Jul;46(7):2652-61. Epub 2011 Apr 3.
In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives.
Shao JW, Dai YC, Xue JP, Wang JC, Lin FP, Guo YH.
Source

Chemistry and Chemical Engineering College of Fuzhou University, #2, Xueyuan Road, Fuzhou 350108, PR China. shaojingwei@fzu.edu.cn
Abstract

Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight. The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 ± 4.3%) compared to the control group.

Copyright © 2011 Elsevier Masson SAS. All rights reserved.

PMID:
21514015

Toxicol In Vitro. 2011 Oct;25(7):1274-80. Epub 2011 Apr 20.
Inhibition of cell proliferation, invasion and migration by ursolic acid in human lung cancer cell lines.
Huang CY, Lin CY, Tsai CW, Yin MC.
Source

Department of Nutrition, China Medical University, Taichung City, Taiwan, ROC.
Abstract

Ursolic acid (UA) is a pentacyclic triterpene naturally occurring in many plant foods. Apoptotic, anti-invasive and anti-migratory effects of UA at 2, 4, 8, or 16 μmol/L in human non-small cell lung cancer A549, H3255 and Calu-6 cell lines were examined. The impact of this compound upon associated biomarkers such as vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase (MMP) was also evaluated. UA treatments concentration-dependently decreased cell viability, and lowered Na(+)-K(+)-ATPase activity (P<0.05). This compound at 4-16 μmol/L concentration-dependently increased DNA fragmentation, and reduced VEGF and transforming growth factor beta1 levels in test cancer cells (P<0.05). UA concentration-dependently suppressed ICAM-1 expression (P<0.05). This compound significantly declined fibronectin expression (P<0.05), but concentration-dependent effect was shown in H3255 cells only (P<0.05). UA treatments significantly suppressed the expression of MMP-9 and MMP-2 (P<0.05), and inhibited protein kinase C activity in test cell lines (P<0.05). UA treatments also concentration-dependently reduced cell invasion (P<0.05); however, this compound at 4-16 μmol/L significantly decreased cell migration (P<0.05), and concentration-dependent effect was shown in A549 and Calu-6 cells (P<0.05). These findings suggested that this triterpene was a potent anti-lung cancer agent, and it might be able to retard invasion and metastasis of lung cancer cells.

Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID:
21539908

Antioxidant + skyddar hjärtat

J Nat Prod. 2011 Jul 22;74(7):1640-4. Epub 2011 Jun 7.
Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria.
Liobikas J, Majiene D, Trumbeckaite S, Kursvietiene L, Masteikova R, Kopustinskiene DM, Savickas A, Bernatoniene J.
Source

Institute for Biomedical Research, Academy of Medicine, Lithuanian University of Health Sciences, Eiveniu 4, LT-50009, Kaunas, Lithuania.
Abstract

Ursolic acid (1), a pentacyclic triterpene acid, is one of the major components of certain traditional medicinal plants and possesses a wide range of biological effects, such as anti-inflammatory, antioxidative, and cytotoxic activities. Furthermore, 1, when present at 1.6-5 ng/mL concentrations in commercial herbal preparations used for patients with cardiac disorders, may also exert pro-cardiac activities. There are several indirect suggestions that the cardioprotective mechanism of ursolic acid could involve the mitochondria; however the mechanism of action is still not known. Therefore, the effects of 0.4-200 ng/mL ursolic acid (1) on the functions of isolated rat heart mitochondria oxidizing either pyruvate and malate, succinate, or palmitoyl-l-carnitine plus malate were investigated. It was found that 1 induced a statistically significant uncoupling of oxidative phosphorylation. A statistically significant decrease in H₂O₂ production in the mitochondria was observed after incubation with 5 ng/mL 1. This effect was comparable to the effectiveness of the classical uncoupler carbonyl cyanide 3-chlorophenylhydrazone. Since mild mitochondrial uncoupling has been proposed as one of the mechanisms of cardioprotection, the present results indicate that ursolic acid (1) has potential use as a cardioprotective compound.

PMID:
21648406

Hugger en sån!