Oleanolic acid induces relaxation and calcium‐independent release of endothelium‐derived nitric oxide

Rodríguez‐Rodríguez, Rosalía; Stankevičius, Edgaras; Herrera, Marcelino; Østergaard, Leif; Andersen, Malene R.; Ruı́z-Gutı́errez, Valentina; Simonsen, Ulf

doi:10.1038/bjp.2008.289

Cited by 57 publications

(51 citation statements)

References 44 publications

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“…The mechanism of such activity has been designated as taking place through NF-κB transactivation and calcium-independent mechanisms. Moreover, triterpenoids upregulated the NO accumulation in www.journals.viamedica.pl/ophthalmology_journal a dose-dependent manner [17,18]. These results are also closely connected and confirm those respecting apoptosis level because NO is a recognised compound that induces apoptosis through changes in the expression of pro-apoptotic proteins like P53 or Bax [18].…”

Section: Oa and Ua Impact On Production Of Metalloproteinases (Mmp-2 supporting

confidence: 75%

The impact of oleanolic and ursolic acid on corneal epithelial cells in vitro

et al. 2017

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introduCtion. Oleanolic (OA) and ursolic (UA) acids belong to the triterpene group widely present in plants. These compounds are recognised to have anti-inflammatory properties and thus are considered to be used in therapies as well as in cosmetic, natural health, or diet products. aiM. The scientific hypothesis of our study was to show that OA and UA influence corneal epithelial cells cultured in vitro. Methods. Toxicity tests, based on MTT and Neutral Red (NR) uptake, measurement of nitric oxide (NOx) level, as well as analysis of metalloproteinases (MMP-2 and MMP-9) amount and activity were performed. resuLts. UA expressed significantly higher toxicity on cells than OA. At the lowest concentration applied (5 µM), UA limited cellular metabolism and viability on average by 22% as compared to untreated control, while 25 µM resulted in values lower than 10%. On the other hand, OA at the highest (100 µM) concentration limited cellular metabolism and viability by about 20%. NOx level significantly increased when OA and UA were applied at concentrations of 25 and 100 µM, respectively. OA and UA had a stronger impact on the level of MMP-2 than MMP-9. OA and UA reduced MMP-2 and MMP-9 in the whole range of concentrations. Tested triterpenoids had no significant impact on MMP activity. ConCLusions. OA and UA have a different impact on human corneal epithelial cells. UA is toxic for corneal epithelial cells, while OA exhibits milder activity, which may be useful for further analysis in ocular pharmacology.

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Section: Oa and Ua Impact On Production Of Metalloproteinases (Mmp-2 supporting

confidence: 75%

The impact of oleanolic and ursolic acid on corneal epithelial cells in vitro

et al. 2017

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“…Measurements of intracellular calcium levels were performed in mesenteric small arteries as previously described elsewhere (Rodriguez-Rodriguez et al, 2008). After mounting, equilibration, and normalization, the arteries were loaded with Fura-2 AM (8 mM) and loading mix (Pluronic F127) in the dark for 2 hours.…”

Section: Methodsmentioning

confidence: 99%

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide-Induced Relaxation of Rat Mesenteric Small Arteries

Hedegaard

Gouliaev

Winther

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Endogenous hydrogen sulfide (H 2 S) is involved in the regulation of vascular tone. We hypothesized that the lowering of calcium and opening of potassium (K) channels as well as calciumindependent mechanisms are involved in H 2 S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H 2 S] after addition to closed tubes of sodium hydrosulfide (NaHS), Na 2 S, and GYY4137 [P-(4-methoxyphenyl)-P-4-morpholinyl-phosphinodithioic acid] were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H 2 S], GYY4137 caused more relaxation in relation to released free H 2 S than NaHS and Na 2 S in rat mesenteric small arteries. Simultaneous measurements of [H 2 S] and tension showed that 15 mM of free H 2 S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaHS lowered calcium and caused relaxation of NE-contracted arteries, while high extracellular potassium reduced NaHS relaxation without corresponding calcium changes. In NE-contracted arteries, NaHS (1 mM) lowered the phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 remained unchanged. Protein kinase A and G, inhibitors of guanylate cyclase, failed to reduce NaHS relaxation, whereas blockers of voltage-gated K V 7 channels inhibited NaHS relaxation, and blockers of mitochondrial complex I and III abolished NaHS relaxation. Our findings suggest that low micromolar concentrations of free H 2 S open K channels followed by lowering of smooth muscle calcium, and by another mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation.

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“…OA has numerous beneficial properties, including anti-cancer, hepatoprotective, hypolipidemic [94,95] , antioxidative, anti-inflammatory [96] , endothelial protective [97] , and antiatherosclerotic effects.…”

Section: Oleanolic Acid (Oa)mentioning

confidence: 99%

Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives

et al. 2017

Acta Pharmacol Sin

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Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors.

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Oleanolic acid induces relaxation and calcium‐independent release of endothelium‐derived nitric oxide

Cited by 57 publications

References 44 publications

The impact of oleanolic and ursolic acid on corneal epithelial cells in vitro

The impact of oleanolic and ursolic acid on corneal epithelial cells in vitro

Involvement of Potassium Channels and Calcium-Independent Mechanisms in Hydrogen Sulfide-Induced Relaxation of Rat Mesenteric Small Arteries

Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives

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