Increased warfarin anticoagulant activity and its potential interaction with aqueous extract of goji berry (Lycium barbarum L.) in Wistar rats

Authors

DOI:

https://doi.org/10.33448/rsd-v9i12.11070

Keywords:

Delivery of health care; Food-drug interactions; Prothrombin time; Venous thromboembolism.

Abstract

The consumption of goji berry (Lycium barbarum L.) has aroused worldwide interest due to its excellent nutritional and functional properties, related to the reduced risk of developing chronic diseases due to oxidative stress, being classified as a “super food”. Thus, the aim of this study was to evaluate the effects of aqueous extract of goji berry on hematological and biochemical parameters in Wistar rats treated with warfarin. The concentration of total phenols was determined by the Folin-Ciocalteau reagent, while the antioxidant capacity determined by the DPPH test. The animals were divided into four experimental groups: distilled water (vehicle - negative control); fed daily with the extract (0.18 g.Kg-1); treated daily with water and warfarin (0.5 mg.Kg-1 - positive control) and those treated concomitantly with the extract and warfarin, for seven days. Our results showed a high amount of polyphenols (6.19 ± 0.3 mg EAG.g-1) in the 10 % aqueous extract (m.v-1) and suggests considerable antioxidant activity (IC50 1068 µg.mL-1). We did not observe significant differences between the biochemical and hematological profiles, or even signs of toxicity of the extract when administered alone. The data from concomitant use with warfarin are impressive and show a significant increase in prothrombin time, with the potential for bleeding. Collectively, these observations suggest the propensity for a clinically important interaction between warfarin and Lycium barbarum L., which compromises the safety of this drug and sheds light on future research related to a deeper understanding of the molecular mechanisms involved.

References

Abuduaibifu, A., & Tamer, C. E. (2019). Evaluation of physicochemical and bioaccessibility properties of goji berry kombucha. Journal of Food Processing and Preservation, 43(9), e14077. https://doi.org/10.1111/jfpp.14077.

Ahad, H., Jin, H., Liu, Y., Wang, J., Sun, G., Liang, X., & Aisa, H. A. (2020). Chemical profiling of spermidines in goji berry by strong cation exchange solid-phase extraction (SCXSPE) combined with ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS/MS). Journal of Chromatography B, 1137, 121923. https://doi.org/ 10.1016/j.jchromb.2019.121923.

Alara, O. R., Mudalip, S. K. A., Abdurahman, N. H., Mahmoud, M. S., & Obanijesu, E. O. (2019). Data on parametric influence of microwave-assisted extraction on the recovery yield, total phenolic content and antioxidant activity of Phaleria macrocarpa fruit peel extract. Chemical Data Collections, 24(1), 100277-100284. https://doi.org/10.1016/j.cdc.2019.100277.

Amagase, H., & Farnsworth, N. R. (2011). A review of botanical characteristics, phytochemistry, clinical relevance in efficacy and safety of Lycium barbarum fruit (Goji). Food Research International, 44(7), 1702-1717. https://doi.org/10.1016/

j.foodres.2011.03.027.

Annadurai, P., Annadurai, V., Yongkun, M., Pugazhendhi, A., & Dhandayuthapani, K. (2021). Phytochemical composition, antioxidant and antimicrobial activities of Plecospermum spinosum Trecul. Process Biochemistry, 100(1), 107-116. https://doi.org/10.1016/j.procbio.2020.09.031.

Baker, W., Cios, D. A., Sander, S. D., & Coleman, C. I. (2009). Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. Journal of Managed Care Pharmacy, 15(3), 244-252. https://doi.org/ 10.18553/jmcp.2009.15.3.244.

Benchennouf, A., Grigorakis, S., Loupassaki, S., & Kokkalou, E. (2016). Phytochemical analysis and antioxidant activity of Lycium barbarum (Goji) cultivated in Greece. Pharmaceutical Biology, 55(1), 596-602. https://doi.org/10.1080/13880209.2016.1265987.

Blasi, F., Montesano, D., Simonetti, M. S., & Cossignani, L. (2017). A simple and rapid extraction method to evaluate the fatty acid composition and nutritional value of goji berry lipid. Food Analytical Methods, 10(4), 970-979. https://doi.org/10. 1007/s12161-016-0652-x.

Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochemistry, 72(1-2), 248-254. https://doi.org/10.1016/0003-2697(76)90527-3.

Cañizares, L. C. C., Timm, N. S., Ramos, A. H., Neutzling, H. P., Ferreira, C. D., & Oliveira, M. (2020). Effects of moisture content and expansion method on the technological and sensory properties of white popcorn. International Journal of Gastronomy and Food Science, 22, 100282. https://doi.org/10.1016/j.ijgfs.2020. 100282.

Conidi, C., Drioli, E., & Cassano, A. (2020). Coupling ultrafiltration-based processes to concentrate phenolic compounds from aqueous goji berry extracts. Molecules, 25(16), 3761. https://doi.org/10.3390/molecules25163761.

Denger, A. P. F. L., Kawano, L. O., Paula, R. A. O., Santos, L. B., Rodrigues, M. R., Paula, F. B. A., Duarte, S. M. S. Determinação da atividade antioxidante e de fenóis totais do pequi (Caryocar brasiliense Camb.) Research, Society and Development, 9(11), e 2859119781. https://doi.org/10.33448/rsd-v9i11.9781.

Donno, D., Beccaro, G. L., Mellano, M. G., Cerutti, A. K., & Bounous, G. (2015). Goji berry fruit (Lycium spp.): antioxidant compound fingerprint and bioactivity evaluation. Journal of Functional Foods, 18(B), 1070-1085. https://doi.org/10.1016/ j.jff.2014.05.020.

European Pharmacopoeia Commission (2019). Barbary wolfberry fruit: Lycii fructus. In: European Pharmacopoeia Commission. European pharmacopoeia. (10. Ed., pp. 1332-1333). Strasbourg: Council of Europe.

Food Ingredients & Packaging (2019, Jun. 9). Generally Recognized as Safe (GRAS). Recuperado em: 04 de dezembro 2020, de https://www.fda.gov/ food/food-ingredientspackaging/generally-recognized-safe-gras.

Forino, M., Tartaglione, L., Dell’Aversano, C., & Ciminiello, P. (2016). NMR-based identification of the phenolic profile of fruits of Lycium barbarum (goji berries). Isolation and structural determination of a novel N-feruloyl tyramine dimer as the most abundant antioxidant polyphenol of goji berries. Food Chemistry, 194, 1254-1259. https://doi.org/10.1016/j.foodchem.2015.08.129.

Ge, X., Jing, L., Zhao, K., Su, C., Zhang, B., Zhang, Q., Han, L., Yu, X., & Li, W. (2021, Jan 15). The phenolic compounds profile, quantitative analysis and antioxidant activity of four naked barley grains with different color. Food Chemistry, 335, 127655.

https://doi.org/10.1016/j.foodchem.2020.127655.

Gobbo-Neto, L., & Lopes, N. P. (2007). Plantas medicinais: fatores de influência no conteúdo de metabólitos secundários. Química Nova, 30(2), 374-381. http://dx.doi.org/10.1590/S0100-40422007000200026. Recuperado em 15 out. 2020 de https://www.scielo.br/pdf/qn/v30n2/25.pdf.

Guo, Y., Amorati, R., & Valgimigli, L. (2020, Oct. 26). Synergic antioxidant activity of γterpinene with phenols and polyphenols enabled by hydroperoxyl radicals. Food Chemistry. https://doi.org/10.1016/j.foodchem.2020.128468.

Hatano, T., Kagawa, H., Yasuhara, T., & Okuda T. (1988). Two new flavonoids and other constituents in licorice root: their relative astringency and radical scavanging effects. Chemical Pharmaceutical Bulletin, 36(6), 2090-2097. https://doi.org/10.1248/cpb.36.2090.

Inbaraj, B. S., Lu, H., Hung, C. F., Wu, W. B., Lin, C. L., & Chen, B. H. (2008). Determination of carotenoids and their esters in fruits of Lycium barbarum Linnaeus by HPLC DAD-APCI MS. Journal of Pharmaceutical and Biomedical Analysis, 47(4-5), 812-818. https://doi.org/10.1016/j.jpba.2008.04.001.

Kaminsky, L. S., & Zhang, Z.-Y. (1997). Human P450 metabolism of warfarin. Pharmacology & Therapeutics, 73(1), 67-74. https://doi.org/10.1016/s0163-7258(96)00140-4.

Lam, A. Y., Elmer, G. W., & Mohutsky, M. A. (2001). Possible interaction between Warfarin and Lycium Barbarum L. Annals of Pharmacotherapy, 35(10), 1199-1201. https://doi.org/10.1345/aph.1Z442.

Le, K., Chiu, F., & Ng, K. (2007). Identification and quantification of antioxidants in Fructus lycii. Food Chemistry, 105(1), 353-363. https://doi.org/10.1016/j. foodchem.2006.11.063.

Leite, P. M., Castilho, R. O., Ribeiro, A. L. P., & Martins, M. A. P. (2016). Consumption of medicinal plants by patients with heart diseases at a pharmacist-managed anticoagulation clinic in Brazil. International Journal of Clinical Pharmacy, 38(2), 223-227. https://doi.org/10.1007/s11096-016-0270-0.

Leung, H., Hung, A., Hui, A. C. F., & Chan, T. Y. K. (2008). Warfarin overdose due to the possible effects of Lycium barbarum L. Food and Chemical Toxicology, 46(5), 1860-1862. https://doi.org/10.1016/j.fct.2008. 01.008.

Li, H., Zhang, C., Fan, R., Sun, H., Xie, H., Luo, J., Wang, Y., Lv, H., Tang, T. (2016). The effects of Chuanxiong on the pharmacokinetics of warfarin in rats after biliary drainage. Journal of Ethnopharmacology, 193, 117-124. https://doi.org/10.1016/j.jep.2016.08.005.

Llorent-Martínez, E. J., Fernández-de Córdova, M. L., Ortega-Barrales, P., & Ruiz-Medina, A. (2013). Characterization and comparison of the chemical composition of exotic superfoods. Microchemical Journal, 110, 444-451. https://doi.org/10.

/j.microc.2013.05.016.

Lopatriello, A., Previtera, R., Pace, S., Werner, M., Rubino, L., Werz, O., TaglialatelaScafatia, O., & Forino, M. (2017). NMR-based identification of the major bioactive molecules from an Italian cultivar of Lycium barbarum. Phytochemistry, 144, 52-57. https://doi.org/10.1016/j.phytochem.2017.08.016.

Lou, X., Xu, H., Hanna, M., & Yuan, L. (2020). Identification and quantification of free, esterified, glycosylated and insoluble-bound phenolic compounds in hawthorn berry fruit (Crataegus pinnatifida) and antioxidant activity evaluation. LWT, 130, 109643. https://doi.org/10.1016/j.lwt.2020. 109643.

Mocan, A., Moldovan, C., Zengin, G., Bender, O., Locatelli, M., Simigiotis, M., Atalay, A., Vodnar, D. C., Rohn, S., & Crisan, G. (2018). UHPLC-QTOF-MS analysis of bioactive constituents from two Romanian Goji (Lycium barbarum L.) berries cultivars and their antioxidant, enzyme inhibitory, and real-time cytotoxicological evaluation. Food and Chemical Toxicology, 115, 414-424. https://doi.org/10.1016/j.fct.2018.01.054.

Montesano, D., Cossignani, L., Giua, L., Urbani, E., Simonetti, M. S., & Blasi, F. (2016). A simple HPLC-ELSD method for sugar analysis in Goji Berry. Journal of Chemistry, 2016(3), 1-5. https://doi.org/10.1155/2016/6271808.

Navajas-Porras, B., Pérez-Burillo, S., Morales-Pérez, J., Rufián-Henares, J. A., & Pastoriza, S. (2020). Relationship of quality parameters, antioxidant capacity and total phenolic content of EVOO with ripening state and olive variety. Food Chemistry, 325(1), 126926-126939. https://doi.org/10.1016/j.foodchem.2020.126926.

Nieva-Rchevarría, B., Goicoechea, E., & Guillén, M. D. (2017). Effect of liquid smoking on lipid hydrolysis and oxidation reactions during in vitro gastrointestinal digestion of European sea bass. Food Research International, 97(1), 51-61. https://doi.org/10.1016/j.foodres.2017.03.032.

Olszowy, M. (2019). What is responsible for antioxidant properties of polyphenolic compounds from plants? Plant Physiology and Biochemistry, 144(1), 135-143. https://doi.org/10.1016/j.plaphy.2019.09.039.

Pedro, A. C., Sánchez-Mata, M-C., Pérez-Rodríguez, M. L., Cámara, M., López-Colón, J. L., Bach, F., Bellettini, M., Haminiuk, C. W. I. (2019). Qualitative and nutritional comparison of goji berry fruits produced in organic and conventional systems. Scientia Horticulturae, 257(1), 108660-108668. http://dx.doi.org/10.1016/j.scienta.2019.108660.

Pereira, A. S., Shitsuka, M. S., Pereira, F. J., Shitsuka, R. (2018). Metodologia da pesquisa científica. [e-book]. Santa Maria. Ed. UAB/NTE/UFSM. Disponível em: https://repositorio.ufsm.br/bitstream/handle/1/15824/Lic_Computacao_MetodologiaPesquisa-Cientifica.pdf?sequence=1.

Piatkov, I., Rochester, C., Jones, T., & Boyages, S. (2010). Warfarin toxicity and individual variability: clinical case. Toxins, 2(11), 2584-2592. https://doi.org/ 10.3390/toxins2112584.

Pirmohamed, M., Kamali, F., Daly, A. K., & Wadelius, M. (2015). Oral anticoagulation: a critique of recent advances and controversies. Trends in Pharmacological Sciences, 36(3), 153-163. https://doi.org/10.1016/j.tips. 2015.01.003.

Pogačnik, L., Ota, A., & Ulrih, N. P. (2020). An overview of crucial dietary substances and their modes of action for prevention of neurodegenerative diseases. Cells, 9(3), 576. https://doi.org/10.3390/cells9030576.

Protti, M., Gualandi, I., Mandrioli, R., Zappoli, S., Tonelli, D., & Mercolini, L. (2017). Analytical profiling of selected antioxidants and total antioxidant capacity of goji (Lycium spp.) berries. Journal of Pharmaceutical and Biomedical Analysis, 143, 252-260. https://doi.org/10.1016/j.jpba.2017.05.048.

Qian, J.-Y., Liu, D., & Huang, A. (2004). The efficiency of flavonoids in polar extracts of Lycium chinense Mill fruits as free radical scavenger. Food Chemistry, 87(2), 283-288. https://doi.org/10.1016/j.foodchem.2003.11.008.

Quick, A. J., Stanley-Bronwn, M., & Bancroft, F. W. (1935). A study of the coagulation defect in hemophilia and in jaundice. American Journal of the Medical Sciences, 190(4), 501-511. https://doi.org/10.1055/s-0038-1650068.

Rasool, A., Zulfajric, M., Gulzard, A., Hanafiahef, M. M., Unnisab, S. A., & Mahbooba, M. (2020). In vitro effects of cobalt nanoparticles on aspartate aminotransferase and alanine aminotransferase activities of wistar rats. Biotechnology Reports, 26, e00453. https://doi.org/10.1016/j.btre.2020.e00453.

Ren, Z., Na, L., Xu, Y., Rozati, M., Wang, J., Xu, J., Sun, C., Vidal, K., Wu, D., & Meidani, S. N. (2012). Dietary supplementation with lacto-wolfberry enhances the immune response and reduces pathogenesis to influenza infection in mice. The Journal of Nutrition. 142(8), 1596-1602. https://doi.org/10.3945/jn.112.159467.

Rivera, C. A., Ferro, C. L., Bursua, A. J., & Gerber, B. S. (2012). Probable interaction between Lycium barbarum (Goji) and Warfarin. Pharmacotherapy, 32(3), 50-53. https://doi.org/10.1002/j.1875-9114.2012.01018.x.

Rocchetti, G., Chiodelli, G., Giuberti, G., Ghisoni, S., Baccolo, G., Biasi, F, Montesano, D., Trevisan, M., & Lucini, L. (2018). UHPLC-ESI-QTOF-MS profile of polyphenols in Goji berries (Lycium barbarum L.) and its dynamics during in vitro gastrointestinal digestion and fermentation. Journal of Functional Foods, 40, 564-572. https://doi.org/10.1016/j.jff.2017.11.042.

Rudasill, S. E., Liu, J., & Kamath, A. F. (2019). Revisiting the International Normalized Ratio (INR) threshold for complications in primary total knee arthroplasty: an analysis of 21,239 cases. The Journal of Bone and Joint Surgery: American Volume, 101(6), 514-522. https://doi.org/10.2106/JBJS.18.00771.

Sherkatolabbasieh, H., Firouzi, M., & Shafizadeh, S. (2020). Evaluation of platelet count, erythrocyte sedimentation rate and C-reactive protein levels in paediatric patients with inflammatory and infectious disease. New Microbes and New Infections, 37, 100725. https://doi.org/10.1016/j.nmni.2020.100725.

Silva, V. M., Rezende, D. C., Garcia, E. S., Cavalheiro, C., & Strunz, C. C. (2020). Effect of anticoagulant adjustment on prothrombin time test using two different PT reagents in patients with elevated hematocrit. Practical Laboratory Medicine, 22, e00177. https://doi.org/10.1016/j.plabm.2020.e00177.

Skenderidis, P., Lampakis, D., Giavasis, I., Leontopoulos, S., Petrotos, K., Hadjichristodoulou, C., & Tsakalof, A. (2019). Chemical properties, fatty-acid composition, and antioxidant activity of Goji Berry (Lycium barbarum L. and Lycium chinense Mill.) fruits. Antioxidants, 8(3), 60. https://doi.org/10.3390/ antiox8030060.

Tang, W.-M., Chan, E., Kwok, C.-Y., Lee, Y.-K., Wu, J.-H., Wan, C.-W., Chan, R. Y.-K., Yu, P. H.-F., & Chan, S.-W. (2012). A review of the anticancer and immunomodulatory effects of Lycium barbarum fruit. Inflammopharmacology, 20, 307-314.

https://doi.org/10.1007/s10787-011-0107-3.

Tang, H.-L., Chen, C., Wang, S.-K., & Sun, G.-J. (2015). Biochemical analysis and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L. International Journal of Biological Macromolecules, 77, 235-242.

https://doi.org/10.1016/j.ijbiomac.2015.03.026.

Tsikas, D. (2017). Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: analytical and biological challenges. Analytical Biochemistry, 524, 13-30. https://doi.org/10.1016/j.ab.2016.10.021.

Ulbricht, C., Chao, W., Costa, D., Rusie-Seamon, E., Weissner, W., & Woods, J. (2008). Clinical evidence of herb-drug interactions: a systematic review by the natural standard research collaboration. Current Drug Metabolism, 9(10), 1063-1120. https://doi.org/10.2174/138920008786927785.

Wang, C. C., Chang, S. C., Inbaraj, B.S., & Chen, B. H. (2010). Isolation of carotenoids, flavonoids and polysaccharides from Lycium barbarum L. and evaluation of antioxidant activity. Food Chemistry, 120(1), 184-192. https://doi.org/10.1016/j.foodchem.2009.10.005.

Wang, H., Zhang, S., Shen, Q., & Zhu, M.-J. (2019). A metabolomic explanation on beneficial effects of dietary Goji on intestine inflammation. Journal of Functional Foods, 53, 109-114. https://doi.org/10.1016/j.jff.2018. 12.014.

Winterbourn, C. C., Gutteridge, J. M., & Halliwell, B. (1985). Doxorubicin dependent lipid peroxidation at low partial pressures of O2. Journal of Free Radicals in Biology and Mededicine, 1(1), 43-49. https://doi.org/10.1016/0748-5514(85)90028-5.

Woisk, R. G., & Salatino, A. (1998). Analisys of própolis: some parameters and procedures for chemical quality control. Journal of Apicultural Research, 37(2), 99-105. https://doi.org/10.1080/00218839.1998.11100961.

Wojdyło, A., Nowicka, P., & Bąbelewski, P. (2018). Phenolic and carotenoid profile of new goji cultivars and their anti-hyperglycemic, anti-aging and antioxidant properties. Journal of Functional Foods, 48, 632-642. https://doi.org/ 10.1016/j.jff.2018.07.061.

Wu, D. T., Guo, H., Lin, S., Lam, S. C., Zhao, L., Lin, D. R., Qin, Wen. (2018). Review of the structural characterization, quality evaluation, and industrial application of Lycium barbarum polysaccharides. Trends in Food Science & Technology, 79, 171-183. https://doi.org/10.1016/j.tifs.2018.07.016.

Yang, X., Bai, H., Li, W. C. J., Zhou, Q., Wang, Y., Han, J., Zhu, X., Dong, M., & Hu, D. (2013). Lycium barbarum polysaccharides reduce intestinal ischemia/reperfusion injuries in rats. Chemico-Biological Interactions, 204(3), 166-172.

https://doi.org/10.1016/j.cbi.2013.05.010.

Yang, R., Zhao, C., Chen, X., Chan, S. & Wu, J. (2015). Chemical properties and bioactivities of Goji (Lycium barbarum) polysaccharides extracted by different methods. Journal of Functional Foods, 17, 903-909. tps://doi.org/10.1016/j.jff. 2015.06.045.

Yao, R., Heinrich, M., & Weckerle, C. S. (2018). The genus Lycium as food and medicine: a botanical, ethnobotanical and historical review. Journal of Ethnopharmacology, 212, 50-66. https://doi.org/10.1016/j.jep.2017.10.010.

Zhang, J., Tian, L. & Xie, B. (2015). Bleeding due to a probable interaction between warfarin and Gouqizi (Lycium Barbarum L.). Toxicology Reports, 2, 1209-1212. https://doi.org/10.1016/j.toxrep.2015.08.011.

Zhang, G.-M., Zhang, G.-M., Hu, S., Peng, Y.-F., & Gu, B. (2020). Is testing of aspartate aminotransferase necessary along with every alanine aminotransferase for health check in elderly individuals? Clinica Chimica Acta: International Journal of Clinical Chemistry, 507, 224-227. https://doi.org/10.1016/j.cca.2020.05.003.

Zhang, X., Li, X., Su, M., Du, J., Zhou, H., Li, X., & Ye, Z. (2020). A comparative UPLC-QTOF/MS-based metabolomics approach for distinguishing peach (Prunus persica (L.) Batsch) fruit cultivars with varying antioxidant activity. Food Research International, 137(1), 109531-109543. https://doi.org/10.1016/j.foodres.2020.109531.

Žlabur, J. S., Žutić, I., Radman, S., Pleša, M., Brnčić, M., Barba, F. J., Rochetti, G., Lucini, L., Lorenzo, J. M., Domíngez, R., Brnčić, S. R., Galić, A., & Voća, S. (2020). Effect of different green extraction methods and solvents on bioactive components of chamomile (Matricaria chamomilla L.) flowers. Molecules, 25(4), 810. https://doi.org/10.3390/molecules25040810.

Published

24/12/2020

How to Cite

OLIVEIRA, G. A. de .; CAMILO, M. A.; MARQUES, L. G. .; OLIVEIRA, C. M. de .; FIGUEIREDO, S. A. .; SANTOS, L. B.; PAULA, R. A. de O.; PAULA, F. B. de A. .; RODRIGUES, M. R.; DUARTE, S. M. da S. Increased warfarin anticoagulant activity and its potential interaction with aqueous extract of goji berry (Lycium barbarum L.) in Wistar rats. Research, Society and Development, [S. l.], v. 9, n. 12, p. e29591211070, 2020. DOI: 10.33448/rsd-v9i12.11070. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/11070. Acesso em: 24 may. 2022.

Issue

Section

Health Sciences