Application of Cornelian Cherry Iridoid-Polyphenolic Fraction and Loganic Acid to Reduce Intraocular Pressure
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Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 939402, 8 pages http://dx.doi.org/10.1155/2015/939402 Research Article Application of Cornelian Cherry Iridoid-Polyphenolic Fraction and Loganic Acid to Reduce Intraocular Pressure Dorota Szumny,1,2 Tomasz SozaNski,1 Alicja Z. Kucharska,3 Wojciech Dziewiszek,1 Narcyz Piórecki,4,5 Jan Magdalan,1 Ewa Chlebda-Sieragowska,1 Robert Kupczynski,6 Adam Szeldg,1 and Antoni Szumny7 1 Department of Pharmacology, Wrocław Medical University, 50-345 Wrocław, Poland 2Ophthalmology Clinic, Uniwersytecki Szpital Kliniczny, 50-556 Wrocław, Poland 3Department of Fruit and Vegetables Technology, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland 4Arboretum and Institute of Physiography in Bolestraszyce, 37-722 Bolestraszyce, Poland 5Department of Turism & Recreation, University of Rzeszow, 35-959 Rzeszow,´ Poland 6Department of Environment Hygiene and Animal Welfare, Wrocław University of Environmental and Life Sciences, 51-630 Wrocław, Poland 7Department of Chemistry, Wrocław University of Environmental and Life Science, 50-375 Wrocław, Poland Correspondence should be addressed to Dorota Szumny; [email protected] Received 6 February 2015; Revised 21 April 2015; Accepted 12 May 2015 Academic Editor: MinKyun Na Copyright © 2015 Dorota Szumny et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. One of the most common diseases of old age in modern societies is glaucoma. It is strongly connected with increased intraocular pressure (IOP) and could permanently damage vision in the affected eye. As there are only a limited number of chemical compounds that can decrease IOP as well as blood flow in eye vessels, the up-to-date investigation of new molecules is important. The chemical composition of the dried Cornelian cherry (Cornus mas L.) polar, iridoid-polyphenol-rich fraction was investigated. Loganic acid (50%) and pelargonidin-3-galactoside (7%) were found as the main components. Among the other constituents, iridoid compound cornuside and the anthocyans cyanidin 3-O-galactoside, cyanidin 3-O-robinobioside, and pelargonidin 3-O-robinobioside were quantified in the fraction. In an animal model (New Zealand rabbits), the influence of loganic acid and the polyphenolic fraction isolated from Cornelian cherry fruit was investigated. We found a strong IOP-hypotensive effect for a 0.7% solution of loganic acid, which could be compared with the widely ophthalmologically used timolol. About a 25% decrease in IOP was observed within the first 3 hours of use. 1. Introduction published studies demonstrate that a reduction in IOP is associated with a lower risk of glaucoma progression, owing The term “glaucoma” involves a range of diseases associated to the less rapid optic nerve damage and reduced loss of with progressive optic nerve damage, including typical mor- the visual field5 [ –7]. Pressure reduction offered by the phological changes of its disk and characteristic loss of the currently used medication is based on reduced production field of vision, which are often accompanied by increased or increased outflow of aqueous media [8], some of which intraocular pressure (IOP) [1]. Risk factors of glaucoma- also have neuroprotective properties or are able to improve associated optic nerve damage include increased IOP,positive vascular flow. Nowadays, the following groups of medication family history, systemic arterial hypotension or hypertension, areusedforglaucomatreatment:-adrenergic receptor and ischaemia-aggravating diseases such as diabetes [2, 3]. antagonists, prostaglandin analogues, 2-adrenergic receptor The maintenance of IOP at a desired level is particu- agonists, carbonic anhydrase inhibitors, cholinergic agents, larly important in the therapy of glaucoma [4]. Results of and hyperosmotic drugs [9, 10]. 2 Evidence-Based Complementary and Alternative Medicine Onlyafewstudieshavebeenaimedattheeffectof 2. Materials and Methods compounds of natural origin on the IOP, as well as other glaucoma-progressing factors, such as vascular blood flow, 2.1. Evaluation of Cornelian Cherry Constituents. Raciborski- antioxidative effects, or neuroprotection. The majority of variety Cornelian cherries (Cornus mas L.) were obtained these studies were conducted in vitro,butafewwerein fromtheBolestraszyceArboretumandInstituteofPhys- vivo and reached clinical trials. The difficulties encountered iography, Poland, in September 2012. The plant material in the evaluation of natural compounds on the progress of was authenticated by Professor Jakub Dolatowski, and the glaucoma-associated neuropathy are a consequence of long- voucher specimen (12402) was deposited at the Herbarium term disease development but are also because of the limited of Arboretum and Institute of Physiography in Bolestraszyce, possibility to use proper animal models [11, 12]. Poland. The polyphenolic and loganic acid iridoid fractions One of several plant-origin compounds with a proven were prepared in the Department of Fruit, Vegetable and IOP-reducing effect is forskolin, which is obtained from Cereals Technology at Wroclaw University of Environmental Coleus forskohlii (Lamiaceae). Following intraconjunctival and Life Science, according to the procedure described in administration, the compound stimulates adenylate cyclase, our previous publication [29]andpatent[29]. Ripe Cor- − ∘ which leads to the activation of cyclic adenosine monophos- nelian cherries were washed, frozen, and stored at 20 C phateinciliaryepitheliumandthereductionofIOP,resulting until processing. After freezing, removing stones, defrosting, from reduced production of aqueous products in rabbits, and depectinisation, we obtained the juice. The juice was monkeys, and humans [13, 14]. Similarly, natural bromophe- purifiedonanAmberliteXAD-16resincolumn.Iridoids nols isolated from red algae belonging to the Rhodomelaceae and phenolics were eluted with 80% ethanol. The eluent was ∘ family, such as vidalol B, present activity as carbonic anhy- concentrated under vacuum at 40 C and lyophilised. About drase inhibitors and may become a valuable IOP-reducing 20 g of lyophilisate from the iridoid-polyphenolic fraction drug in the future [15]. Recently, marijuana was considered was obtained from 5 kg of fruit. After freeze drying, the as an IOP-reducing natural compound. However, because of a samples were ground into a powder using a laboratory mill. high ratio of nonresponders, short half-life, and considerable The structure of the compounds in the iridoid-phenolic toxicity, the substance was not qualified for medicinal use fraction was determined by UPLC-MS analysis. [16–18]. Among other plants, Ginkgo biloba leaf extracts may be used for adjunct glaucoma therapy. The extract contains polyphenolic flavonoid compounds, as well as terpenoids, 2.2. Isolation of Anthocyan-Irdoid Fraction and Pure Loganic and is able to scavenge free radicals at the mitochondrial level Acid. The easy, effective, and low-cost approach for isolation in order to improve blood flow. In addition, the substance ofloganicacidaswellastheanthocyaninfractionwas prevents neurotoxicity of glutamate, which may be important developed in our research group [30]. In brief, freeze-died for a neuroprotective effect, and inhibits lipid peroxidation Cornelian fruit powder (as described above) was dissolved [19, 20]. Although it does not affect the IOP, it may improve in 30% ethanol and separated using column chromatography vascular blood flow into the optic nerve21 [ ]. Clinical trials (polyamide). Elution with 50% ethanol (and 1% acetic acid) have indicated that anthocyanins and Ginkgo biloba extract afforded the anthocyanin fraction and pure loganic acid. maybeeffectiveinimprovingthevisualfunctionandthe Applying the described procedure to 1 kg of fresh fruit visual field of patients with normal-tension glaucoma [20, allowed us to obtain 4.0 g of the anthocyanin fraction and 22]. Nowadays, the only drug of natural origin currently 1.5 g of pure loganic acid. used in glaucoma treatment is pilocarpine, which is the The structure and purity of loganic acid was determined alkaloid from Jaborandi (Pilocarpus microphyllus)leaves.Its by NMR and UPLC-MS analyses. pharmacological activities are connected with properties of a muscarinic agonist with no nicotinic effects [23, 24]. One 2.3. Identification of Compounds by UPLC-MS/MS and HPLC. of the most popular plant extracts traditionally used in eyes Compounds of the phenolic-iridoid and loganic acid frac- diseases in Europe, especially for the inflammation of eyes, tions were identified by applying the method described by is Eyebright (Euphrasia). Its most important constituents Kucharska et al. [30], using the acuity ultra-performance that affect the eyes are iridoid glycosides, including aucubin, liquid chromatography (UPLC) system coupled with a geniposide, catalpol, and luproside [25–27]. Although there quadrupole time-of-flight (Q-TOF) MS instrument (Waters are no relevant clinical studies, an established traditional use Corp., Milford, MA, USA) with an electrospray ionisation ofthoseeyedropsprovestheirefficacyinconjunctivitis[28]. (ESI) source. Separation was achieved on the Acquity BEH To the best of our knowledge, there is a lack of data C18 column (100 mm × 2.1 mm, i.d. 1.7 mm; Waters). Detec- regarding the effect of loganic