Actividad Inhibitoria De La Hialuronidasa Del Extracto Hidroalcohólico De Piper Peltatum/Hyaluronidase Inhibitor Activity in Hydroalcoholic Extracts of Piper Peltatum

Abstract

Ecuador se ubica en una zona geográfica privilegiada, presenta zonas climáticas bien definidas con características ambientales y geográficas únicas. Estas particularidades hacen que cada región posea sus propios ecosistemas, existiendo así muchas especies vegetales y animales sin investigar. La población hace uso de estos recursos para tratar diversas dolencias como por ejemplo, Piper peltatum utilizada en caso de mordedura de serpiente. El objetivo del estudio fue determinar si los extractos de esta especie presentaban efectos inhibitorios sobre la hialuronidasa, para lo cual se identificó los metabolitos secundarios presentes mediante el tamizaje fitoquímico, se cuantificó la cantidad de fenoles y flavonoides totales a través de métodos espectrofotométricos y se determinó el porcentaje de inhibición tanto sobre la hialuronidasa bovina como la hialuronidasa presente en el veneno de Naja naja atra y Botrox atrox. Se identificó en P. peltatum alcaloides con potencial actividad antimitótica, cumarinas, terpenos, compuestos fenólicos y flavonoides. La cantidad de fenoles totales fue de 14,49±1,2 mg equivalente de ácido gálico/g extracto seco y 14,53±0,208 mg equivalente de Quercetina/g extracto seco de flavonoides. Respecto a la actividad inhibitoria se concluyó que existe mayor inhibición sobre la hialuronidasa bovina, seguida del veneno de Naja naja atra y no de manera significativa sobre B. atrox.


Ecuador is located in a privileged geographical area, it has strongly defined climatic zones with unique environmental and geographical characteristics. These particularities mean that each region has its own ecosystems, so many plant and animal species exist without investigating. The population makes use of these resources to treat various ailments such as Piper peltatum used in case of snakebite. The objective of the study was to determine if extracts of this species has inhibitory effects on hyaluronidase. The secondary metabolites present were identified by phytochemical screening, the amount of phenols and total flavonoids was quantified by spectrophotometric methods, as well as the determination of the inhibition of bovine, Naja naja atra venom and Botrox atrox hyaluronidase. P. peltatum contains alkaloids with potential antimitotic activity, coumarins, terpenes, phenolic compounds and flavonoids. The amount of total phenols was 14.49 ± 1.2 mg gallic acid equivalent / g dry extract and 14.53 ± 0.208 mg Quercetin equivalent /g dry flavonoid extract. Regarding the inhibitory activity, it was concluded that there is greater inhibition on bovine hyaluronidase, followed by Naja naja atra venom and not significantly on B. atrox.


Palabras claves: Piper peltatum, hialuronidasa, Naja naja atra, Extracto, Bothrops atrox.


Keywords: Piper peltatum, hialuronidase, Naja naja atra, extract, Bothrops atrox.

References
[1] Bravo E. La biodiversidad en el Ecuador [Internet]. 2014. Available from: https://dspace.ups.edu.ec/bitstream/123456789/6788/1/LaBiodiversidad.pdf

[2] Ecuador E del. Flora y Fauna [Internet]. Available from: http://www.embassyecuador.eu/site/index.php/es/turismo-inf-general-2/turismo-flora-fauna#

[3] MSP. Gaceta epidemiológica semanal [Internet]. 2017. Available from: http://www.salud.gob.ec/wpcontent/ uploads/2013/02/Gaceta-General-SE50.pdf

[4] Kasturiratne A. The global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med. 2008;5(11):218.

[5] Harrison R, Hargreaves A, Wagstaff S, Faragher B, Lalloo D. Snake envenoming: A disease of poverty. PLoS Negl Trop Dis. 2009;3(12):569.

[6] Abubakar I, Group N-UES. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria. PLoS Negl Trop Dis. 2010;4(7):767.

[7] Williams D. Ending the drought: New strategies for improving the flow of affordable, effective antivenoms in Asia and Africa. J Proteomics. 2011;74(9):1735–1767.

[8] Chippaux J, Williams V, White J. Snake venom variability: Methods of study, results and interpretation. Toxicon. 1991;29(11):1279–303.

[9] Durban J. Profiling the venom gland transcriptomes of Costa Rican snakes by 454 pyrosequencing. BMC Genomics. 2011;12:259.

[10] Durban J. Integrated “omics” profiling indicates that miRNAs are modulators of the ontogenetic venom composition shift in the Central American rattlesnake, Crotalus simus simus. BMC Genomics. 2013;14:234.

[11] Gibbs H, Sanz L, Sovic M, Calvete J. Phylogeny-based comparative analysis of venom proteome variation in a clade of rattlesnakes (Sistrurus sp.). PLoS One. 2013;8(6):67220.

[12] Salud OM de la. Morderduras de serpientes venenosas [Internet]. Notas descriptivas. 2018. Available from: https://www.who.int/es/news-room/fact-sheets/detail/snakebite-envenoming

[13] Zúñiga I, Lozano J. Aspectos clínicos y epidemiológicos de la mordedura de serpientes en México. Evid médica e Investig en salud. 2013;6(4):125–136.

[14] González É, Ortiz C, Sandoval G, Lazo F, Delgadillo J, Rodríguez E, et al. Purificación Y Caracterización Bioquímica De Un Factor De Difusión Presente En El Veneno De La Serpiente Bothrops atrox ( JERGON). Rev Soc Quím Perú. 2013;79(1):3–12.

[15] Mabberley D. The Plant-book. A Portable Dictionary of the Higher Plants. New York: Cambridge University Press; 1997.

[16] Ramirez J, Cartuche L, Morocho V, Aguilar S, Malagon O. Antifungal activity of raw extract and fl avanons isolated from Piper ecuadorense from Ecuador. Rev Bras Farmacogn. 2013;23(2):370–373.

[17] Joly A. Botânica: Introdução a Taxonomía vegetal. São Paulo: Companhia Editora Nacional; 1991.

[18] López A, Sheng D, Towers N. Antifungal activity of benzoic acid derivatives from Piper lanceaefolium. J Nat Prod. 2002;65:62–64.

[19] Jorgensen PM, León-Yáñes S. Catalogue of the Vascular Plants of Ecuador. USA: Missouri Botanical Garden Press; 1999. 779–783 p.

[20] Terreaux C, Gupta M, Hostettman K. Antifungal benzoic acid derivatives from Piper dilatatum. Phytochemistry. 1998;38:350–353.

[21] Dyer L, Richards J, Dodson C. Isolation, synthesis, and evolutionary ecology of Piper amides. In: Piper: A model genus for studies of phytochemistry, ecology, and evolution. New York: Kluwer Academic/Plenum Publishers; 2004. p. 117–139.

[22] Tene V, Malagón O, Vita Finzi P, Vidari G, Armijos C, Zaragoza T. An ethnobotanical survey of medicinal plants used in Loja and Zamora-Chinchipe, Ecuador. J Ethnopharmacol. 2006;111:63–81.

[23] Andrade M, Armijos C, Malagón O, Lucero H. Plantas medicinales silvestres empleadas por la etnia Saraguro en la Parroquia San Lucas, Provincia de Loja-Ecuador. Loja: Editorial UTPL; 2009.

[24] Andrews J. Determination of minimum inhibitory concentrations. J Antimicrob Chemother. 2001;48(1):5–16.

[25] Rover MR, Brown RC. Quantification of total phenols in bio-oil using the Folin-Ciocalteu method. J Anal Appl Pyrolysis. 2013;104:366–371.

[26] Raj K. Evaluation of anti-oxidant activities and total phenol and flavonoid content of the hydro-alcoholic extracts of Rhodiola sp. Pharmacogn J. 2010;2(11):431–435.

[27] Ipek Süntar, Ibrahim Tumen, Osman Ustün, Hikmet Keleş EKA. Appraisal on the wound healing and anti-inflammatory activities of the essential oils obtained from the cones and needles of Pinus species by in vivo and in vitro experimental models. J Ethnopharmacol. 2011;139(2):533–540.

[28] Lee, K.K. Choi JD. The effects of Areca catechu L. extracts on anti-aging. Int J Cosmet Sci. 1999;21:285–294.

[29] Sahasrabudhe A, Deodhar M. Anti-hyaluronidase, anti-elastase activity of Garcinia indica. Int J Bot. 2010;299–303.

[30] Ratnasooriya WD, Abeysekera WP. KM, Ratnasooriya CTD. In vitro anti-hyaluronidase activity of Sri Lankan low grown orthodox orange pekoe grade black tea (Camellia sinensis L.). Asian Pac J Trop Biomed [Internet]. 2014;4(12):959–963. Available from: http://www.sciencedirect.com/science/article/pii/ S2221169115301118

[31] Pilco G, Vinueza D, Acosta K, Sánchez S, Abdo S. Actividad inhibitoria del extracto de geranio (Pelargonium x domesticum) sobre hialuronidasa. In: Libro de memorias V Congreso Internacional de la Ciencia, Tecnología, emprendimiento e innovación. Riobamba; 2018. p. 821–830.

[32] Wu SJ, Ng LT. Antioxidant and free radical scavenging activities of wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) in Taiwan. LWT - Food Sci Technol. 2008;41:323–330.

[33] Boukhris M, Simmonds MSJ, Sayadi S, Bouaziz M. Chemical Composition and Biological Activities of Polar Extracts and Essential Oil of Rose-scented Geranium, Pelargonium graveolens. 2013;1213 (April 2012):1206–1213.

[34] Scott IM, Jensen ÆHR, Philoge BJR, Arnason ÆJT. A review of Piper spp. (Piperaceae) phytochemistry, insecticidal activity and mode of action. 2008;65–75. [35] Semler U, Gross G. Distribution of piperine in vegetative parts of Piper nigrum. Phytochemistry. 1988;27:1566–1567.

[36] Parmar V et al. Phytochemistry of the genus Piper. Phytochemistry. 1997;46(4):597–673.

[37] Robinson T. Metabolism and Function of Alkaloids in Plants Published by: American Association for the Advancement of Science Stable URL: http://www.jstor.org/stable/1738505 Linked references are available on JSTOR for this article: Metabolism and Function of Alkaloids in Plants. 2016;184(4135):430–435.

[38] Sunila E., Kuttan G. Immunomodulatory and antitumor activity of Piper longum Linn. and piperine. J Ethnopharmacol. 2004;90(2–3):339–346.

[39] Oizumi Y, Kajiwara A, Shoji N, Takemoto T. Chemical Abstracts. 1988. P68970 p.

[40] Boukhris M, Simmonds MSJ, Sayadi S, Bouaziz M. Chemical Composition and Biological Activities of Polar Extracts and Essential Oil of Rose-scented Geranium, Pelargonium graveolens. Phyther Res. 2013;27:1206–1213.

[41] Mirallas G. Evaluación De La Actividad Antioxidante Yantiinflamatoria in vitro De Extractos Hidroalcohólicos De Hojas De Myrcianthes hallii. ESPOCH; 2018.

[42] Kuppusamy U., Das N. Inhibitory effects of flavonoids on several venom hyaluronidases. Experientia. 1991;47:13–17.

[43] Torres A. Comprobación De La Actividad Inhibitoria Del Extracto Hidro- Alcohólico De Piper peltatum Sobre Hialuronidasa. 2018.

[44] McDiarmid R, Campbell J, Touré T. Snake Species of the World: A Taxonomic and Geographic Reference. Herpetologists’ League; 1999. 511 p.

[45] Pithayanukul P, Ruenraroengsak, Pakatip. Bavovada R, Pakmanee N, Suttisri R, Saen-oon S. Inhibition of Naja kaouthia venom activities by plant polyphenols. J Ethnopharmacol. 2005;97(3):527–533.

[46] Kuppusamy UR, Khoo HE, Das N. Structure-activity studies of flavonoids as inhibitors of hyaluronidase. Biochem Pharmacol. 1990;40(2):397–401.