Top

Published in:

01-06-2019 | Bevacizumab | Original Research Article

Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes

Authors: Cibele Rodrigues Toledo, Vinícius Viana Pereira, Lays Fernanda Nunes Dourado, Mayara Rodrigues Brandão Paiva, Armando Silva-Cunha

Published in: Documenta Ophthalmologica | Issue 3/2019

Abstract

Purpose

Investigate the potential application of corosolic acid (CA) in the treatment of diseases causing retinal neovascularization.

Methods

CA cytotoxicity effect was evaluated in ARPE-19 cells by sulforhodamine B colorimetric method, and antiangiogenic activity was studied using chorioallantoic membrane (CAM) assay. An amount of 0.01 mL of CA formulations at 5, 10 and 25 µM was injected in the right eyes of Wistar rats, and the contralateral eyes received the vehicle to verify the safety of ophthalmic use. Electroretinography (ERG) was performed before, 7 and 15 days after CA administration. Animals were killed on the 15th day, and the histological analysis of retina was carried out under light microscopy.

Results

CA did not present cytotoxicity at concentrations below 35.5 μM after 48 h of treatment. The antiangiogenic activity was confirmed by CAM assay, since CA (range from 5 to 25 µM) induced a significant reduction in vascularity without any signs of toxicity. ERG recordings and histological evaluation did not show any signs of retinal toxicity.

Conclusions

CA was effective in reducing vascularity in a CAM model and was found to be safe for potential ophthalmic use.

Delplace V, Payne S, Shoichet M (2015) Delivery strategies for treatment of age-related ocular diseases: from a biological understanding to biomaterial solutions. J Control Release 219:652–668. https://doi.org/10.1016/j.jconrel.2015.09.065 CrossRefPubMed

Bourne RRA, Flaxman SR, Braithwaite T et al (2017) Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Heal 5:e889–e897. https://doi.org/10.1016/S2214-109X(17)30293-0 CrossRef

Behl T, Kotwani A (2015) Possible role of endostatin in the antiangiogenic therapy of diabetic retinopathy. Life Sci 135:131–137. https://doi.org/10.1016/j.lfs.2015.06.017 CrossRefPubMed

Soares DCF, de Paula Oliveira DC, Barcelos LS et al (2017) Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications. Biomed Pharmacother 92:394–402. https://doi.org/10.1016/j.biopha.2017.05.093 CrossRefPubMedPubMedCentral

Gasparin F, Aguiar RG, Lourenc G et al (2014) Pharmacokietics, electrophysiological and morphological effects of the intravitreal injection of mycophenolic acid in rabbits. J Ocul Pharmacol Ther 30:502–511. https://doi.org/10.1089/jop.2013.0236 CrossRefPubMedPubMedCentral

Yoo KH, Park J-H, Lee DY et al (2015) Corosolic acid exhibits anti-angiogenic and anti-lymphangiogenic effects on in vitro endothelial cells and on an in vivo CT-26 colon carcinoma animal model. Phyther Res 29:714–723. https://doi.org/10.1002/ptr.5306 CrossRef

Nazaruk J, Borzym-Kluczyk M (2014) The role of triterpenes in the management of diabetes mellitus and its complications. Phytochem Rev 14(4):675–690. https://doi.org/10.1007/s11101-014-9369-x CrossRefPubMedPubMedCentral

Yang J, Leng J, Li JJ et al (2016) Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice. Phytomedicine 23:181–190. https://doi.org/10.1016/j.phymed.2015.12.018 CrossRefPubMed

Li Y, Zhou Z-H, Chen M-H et al (2016) Inhibition of mitochondrial fission and NOX₂ expression prevent NLRP3 inflammasome activation in the endothelium: the role of corosolic acid action in the amelioration of endothelial dysfunction. Antioxid Redox Signal 24:893–908. https://doi.org/10.1089/ars.2015.6479 CrossRefPubMed

10.

Arancibia-Radich J, Peña-Cerda M, Jara D et al (2016) Comparative study of anti-inflammatory activity and qualitative–quantitative composition of triterpenoids from ten genotypes of Ugni molinae. Bol Latinoam y del Caribe Plantas Med y Aromat 15:274–287

11.

Cheng Q, Li H, Li Y et al (2017) CRA (Crosolic Acid) isolated from Actinidia valvata Dunn. Radix induces apoptosis of human gastric cancer cell line BGC823 in vitro via down-regulation of the NF-κB. Food Chem 105:475–485. https://doi.org/10.1016/j.fct.2017.05.021 CrossRef

12.

Klein G, Kim J, Himmeldirk K et al (2007) Antidiabetes and anti-obesity activity of Lagerstroemia speciosa. Evid Complement Altern Med 4:401–407. https://doi.org/10.1093/ecam/nem013 CrossRef

13.

Kim JH, Kim YH, Song GY et al (2014) Ursolic acid and its natural derivative corosolic acid suppress the proliferation of APC-mutated colon cancer cells through promotion of β-catenin degradation. Food Chem Toxicol 67:87–95. https://doi.org/10.1016/j.fct.2014.02.019 CrossRefPubMed

14.

Tan H, Sonam T, Shimizu K (2017) The potential of triterpenoids from loquat leaves (Eriobotrya japonica) for prevention and treatment of skin disorder. Int J Mol Sci 18(5):1030. https://doi.org/10.3390/ijms18051030 CrossRefPubMedCentral

15.

Skehan P, Storeng R, Scudiero D et al (1990) New colorimetric cytotoxicity assay for anti-cancer drug screening. J Natl Cancer Inst 82:1107–1112. https://doi.org/10.1093/jnci/82.13.1107 CrossRef

16.

Zudaire E, Gambardella L, Kurcz C, Vermeren S (2011) A computational tool for quantitative analysis of vascular networks. PLoS ONE 6:1–12. https://doi.org/10.1371/journal.pone.0027385 CrossRef

17.

Bae JH, Hwang AR, Kim CY et al (2017) Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats. PLoS One 12:1–13. https://doi.org/10.1371/journal.pone.0180482 CrossRef

18.

Özer MA, Erişgin Z, Özen S et al (2017) Effects of intravitreous sodium hydrosulfide on intraocular pressure and retinopathy in ocular hypertensive rats. Biotech Histochem 93:8–14. https://doi.org/10.1080/10520295.2017.1373199 CrossRefPubMed

19.

McCulloch DL, Marmor MF, Brigell MG et al (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12. https://doi.org/10.1007/s10633-014-9473-7 CrossRef

20.

Schatz A, Arango-gonzalez B, Fischer D et al (2012) Transcorneal electrical stimulation shows neuroprotective effects in retinas of light-exposed rats. Retina 53(9):5552–5561. https://doi.org/10.1167/iovs.12-10037 CrossRef

21.

Li X, Zhao H, Wang Q et al (2015) Fucoidan protects ARPE-19 cells from oxidative stress via normalization of reactive oxygen species generation through the Ca 2 + -dependent ERK signaling pathway. Mol Med Rep 11:3746–3752. https://doi.org/10.3892/mmr.2015.3224 CrossRefPubMed

22.

Moreno-jiménez I, Hulsart-billstrom G, Lanham SA, Janeczek AA (2016) The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering. Nature 6:1–12. https://doi.org/10.1038/srep32168 CrossRef

23.

Katrancioglu N, Karahan O, Kilic AT et al (2012) The antiangiogenic effects of levosimendan in a CAM assay. Microvasc Res 83:263–266. https://doi.org/10.1016/j.mvr.2012.01.002 CrossRefPubMed

24.

Fialho SL, Souza PAF, Fulgêncio GO et al (2013) In vivo release and retinal safety of intravitreal implants of thalidomide in rabbit eyes and antiangiogenic effect on the chorioallantoic membrane. J Drug Target 21:837–845. https://doi.org/10.3109/1061186X.2013.829074 CrossRefPubMed

25.

Wang Z, Perez M, Caja S et al (2013) A novel extracellular role for tissue transglutaminase in matrix-bound VEGF-mediated angiogenesis. Cell Death Dis 4:e808–e813. https://doi.org/10.1038/cddis.2013.318 CrossRefPubMedPubMedCentral

26.

Manjunathan R, Ragunathan M (2015) Chicken chorioallantoic membrane as a reliable model to evaluate osteosarcoma—an experimental approach using SaOS2 cell line. Biol Proced Online 17:1–13. https://doi.org/10.1186/s12575-015-0022-x CrossRef

27.

Guidolin D, Nico B, Mazzocchi G et al (2004) Order and disorder in the vascular network. Leukemia 18:1745–1750. https://doi.org/10.1038/sj.leu.2403526 CrossRef

28.

Toth CA, Seider MI, Chen X (2016) Intravitreal triamcinolone deposition mimicking frosted branch angiitis : optical coherence tomography findings. Retin J Retin Vitr Dis 36:41–42. https://doi.org/10.1136/bcr-2014-206286.Discussion CrossRef

29.

Boyes WK, Bercegeay M, Degn L et al (2016) Toluene inhalation exposure for 13 weeks causes persistent changes in electroretinograms of Long-Evans rats. Neurotoxicology 53:257–270. https://doi.org/10.1016/j.neuro.2016.02.008 CrossRefPubMedPubMedCentral

30.

Huang W, Collette W, Twamley M et al (2015) Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats. Toxicol Appl Pharmacol 289:525–533. https://doi.org/10.1016/j.taap.2015.10.008 CrossRefPubMed

31.

Nguyen CT, Tsai TI, He Z et al (2016) Simultaneous recording of electroretinography and visual evoked potentials in anesthetized rats. J Vis Exp 113:e54158. https://doi.org/10.3791/54158 CrossRef

32.

Damico F, Scolari M, Ioshimoto G et al (2012) Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits. Clinics 67:931–937. https://doi.org/10.6061/clinics/2012(08)13 CrossRefPubMedPubMedCentral

33.

Peters T, Kim SW, Castro V et al (2017) Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats. Biomaterials 124:157–168. https://doi.org/10.1016/j.biomaterials.2017.02.006 CrossRefPubMed

Title: Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes
Authors: Cibele Rodrigues Toledo
Vinícius Viana Pereira
Lays Fernanda Nunes Dourado
Mayara Rodrigues Brandão Paiva
Armando Silva-Cunha
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Keyword: Bevacizumab
Published in: Documenta Ophthalmologica / Issue 3/2019
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI: https://doi.org/10.1007/s10633-019-09682-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2019

ISCEV extended protocol for the stimulus–response series for light-adapted full-field ERG

The effects of bandpass filtering on the oscillatory potentials of the electroretinogram

ISCEV extended protocol for the stimulus–response series for the dark-adapted full-field ERG b-wave

Diagnosing MELAS requires not only an mtDNA variant but also an appropriate phenotype

Semi-invasive and non-invasive recording of visual evoked potentials in mice

Clinical diagnosis in the era of DNA testing