Disease relevance of Prunol

• We examined the anti-invasive activity of ursolic acid (UA) on the highly metastatic HT1080 human fibrosarcoma cell line [1].
• Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells [2].
• Differential gene expression for investigation of Escherichia coli biofilm inhibition by plant extract ursolic acid [3].
• Administration of ursolic acid in the rat carotid balloon catheter injury model shows a significant inhibition of neointimal hyperplasia [4].
• Using both 96-well microtiter plates and a continuous flow chamber with COMSTAT analysis, 10 microg of ursolic acid/ml inhibited Escherichia coli biofilm formation 6- to 20-fold when added upon inoculation and when added to a 24-h biofilm; however, ursolic acid was not toxic to E. coli, Pseudomonas aeruginosa, Vibrio harveyi, and hepatocytes [3].
• Overall, our results show that ursolic acid can inhibit the growth and metastasis of CRC and further enhance the therapeutic effects of capecitabine through the suppression of multiple biomarkers linked to inflammation, proliferation, invasion, angiogenesis, and metastasis [5].

Psychiatry related information on Prunol

• The feeding behavior of the greenbug was also affected by ursolic acid [6].
• The oral administration of ursolic acid (2.3 mg/kg) produced a significant depressant effect on CNS by reducing spontaneous motor activity and the number and lethality of pentylenetetrazol (PTZ)-induced seizures [7].
• This study demonstrated that the ursolic acid of Origanum majorana L. appeared to be a potent AChE inhibitor in Alzheimer's Disease [8].

High impact information on Prunol

• Similar results were obtained with U0126 and ursolic acid, specific and nonspecific inhibitors of ERK1/2, respectively [9].
• In the study described in the present report, we found that ursolic acid suppressed NF-kappaB activation induced by various carcinogens including tumor necrosis factor (TNF), phorbol ester, okadaic acid, H(2)O(2), and cigarette smoke [10].
• Ursolic acid inhibited DNA binding of NF-kappaB consisting of p50 and p65 [10].
• Thus, overall, our results indicate that ursolic acid inhibits IkappaBalpha kinase and p65 phosphorylation, leading to the suppression of NF-kappaB activation induced by various carcinogens [10].
• Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells [11].

Chemical compound and disease context of Prunol

• The effects of the triterpene acids, ursolic acid and oleanolic acid, on the differentiation of F9 teratocarcinoma stem cells were studied [12].
• The results suggest that multiple mechanisms including modulation of AMPA receptor, protection of mitochondria, decrease in free radical generation, and scavenging of free radicals might be involved in ursolic acid protection against kainate-induced cell toxicity [13].
• Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas) [14].
• In this study, ursolic acid has been evaluated for its hepatoprotective effect against chronic ethanol-mediated toxicity in rats [15].
• (Cynomoriaceae), ursolic acid and its hydrogen malonate were isolated as inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, with 50% inhibitory concentrations (IC50) of 8 and 6 microM, respectively [16].

Biological context of Prunol

• RU486, a potent glucocorticoid receptor antagonist, was used for identifying that ursolic acid-induced down-regulation of matrix metalloproteinase-9 expression is mediated by its binding to glucocorticoid receptor [17].
• The effect of ursolic acid (UA) on tumor cell apoptosis was investigated using HL-60 human promyelocytic leukemia cells as a model cellular system [18].
• These observations are consistent with a binding site for ursolic acid which extends from S3 towards S4 and S5 on the enzyme [19].
• Ursolic acid, the most potent of these compounds, has an inhibition constant of 4-6 microM for hydrolysis of peptide substrates in phosphate-buffered saline [19].
• Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of DNA replication [20].

Anatomical context of Prunol

• Intracellular Ca2+ release mediates ursolic acid-induced apoptosis in human leukemic HL-60 cells [18].
• Ursolic acid (UA), an anti-inflammatory triterpene carboxylic acid, was recently reported to induce the release of pro-inflammatory mediators in resting macrophages (Mvarphi) [21].
• Ursolic acid inhibited [(125)I]-TGF-beta1 receptor binding to Balb/c 3T3 mouse fibroblasts with an IC(50) value of 6.9+/-0.8 microM [22].
• In mouse peritoneal macrophages, human platelets and differentiated HL60 leukemic cells, ursolic acid, at 1 microM, blocks arachidonate metabolism [23].
• Ursolic acid inhibits neointima formation in the rat carotid artery injury model [4].

Associations of Prunol with other chemical compounds

• Treatment with ursolic acid suppressed PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2 [11].
• Since the chemical structure of ursolic acid is very similar to that of dexamethasone, a synthetic glucocorticoid, we investigated whether ursolic acid acts through the glucocorticoid receptor [17].
• With other pentacyclic triterpenes lacking the 11-keto function and/or the carboxyl function on ring A (e.g., amyrin and ursolic acid), no 5-lipoxygenase inhibition was observed [24].
• The carboxy group at position 28 in the pentacyclic-ring system of the triterpenes contributes to binding to HLE, since replacement of this group with a hydroxy group, as in uvaol, the alcohol analogue of ursolic acid, reduces the potency of inhibition [19].
• There were 31 and 17 genes repressed by 10 and 30 microg of ursolic acid/ml, respectively, and 12 genes were consistently repressed that have functions in cysteine synthesis (cysK) and sulfur metabolism (cysD), as well as unknown functions (such as hdeAB and yhaDFG) [3].

Gene context of Prunol

• Anti-invasive activity of ursolic acid correlates with the reduced expression of matrix metalloproteinase-9 (MMP-9) in HT1080 human fibrosarcoma cells [1].
• Ursolic acid enhances nitric oxide and tumor necrosis factor-alpha production via nuclear factor-kappaB activation in the resting macrophages [25].
• Based on the differential gene expression, it was also discovered that sulfur metabolism (through cysB) affects biofilm formation (in the absence of ursolic acid) [3].
• Regulation of the phosphatidylinositol 3-kinase-akt and the mitogen-activated protein kinase pathways by ursolic Acid in human endometrial cancer cells [26].
• The 3-alpha(axial)-epimer of ursolic acid suppressed de novo formation of COX-2, in contrast to naturally occurring 3-beta(equatorial)-ursolic acid [27].

Analytical, diagnostic and therapeutic context of Prunol

• Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by ursolic acid [11].
• In Northern blot analysis, we found that ursolic acid reduced the expression of matrix metalloproteinase-1 and matrix metalloproteinase-3 induced by 2-O-tetradecanoylphorbol-acetate [17].
• Western blot analysis and immunocytochemistry showed that ursolic acid increased glucocorticoid receptor fraction in the nucleus, although it decreased the synthesis of glucocorticoid receptor mRNA [17].
• To investigate the mechanism of this nontoxic inhibition on a global genetic basis, DNA microarrays were used to study the gene expression profiles of E. coli K-12 grown with or without ursolic acid [3].
• A reversed phase HPLC method has been investigated in order to resolve three main pentacyclic triterpene acids (oleanolic-, betulinic- and ursolic acid) found in a lot of plants [28].

References