Vol. 38 Núm. 3 (2025): Revista ION
Artículos

Efecto sinérgico de los grupos flavonoides presentes en la Ortiga (Urtica dioica) con el salicilato de metilo para la formulación de una crema de uso tópico – Revisión sistemática

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  • Wilfrethd Andrés Suárez Trujillo,
  • Claudia Yolanda Reyes
Wilfrethd Andrés Suárez Trujillo
Universidad de la Amazonia, Colombia
Claudia Yolanda Reyes
Universidad de la Amazonia, Colombia
DOI: https://doi.org/10.18273/revion.v38n3-2025005

Publicado 2026-05-13

Palabras clave

  • Antinflamatorio,
  • Antioxidante,
  • Analgésico,
  • Flavonoides,
  • Antimicrobiano

Cómo citar

Suárez Trujillo, W. A., & Reyes, C. Y. (2026). Efecto sinérgico de los grupos flavonoides presentes en la Ortiga (Urtica dioica) con el salicilato de metilo para la formulación de una crema de uso tópico – Revisión sistemática. Revista ION, 38(3), 61–73. https://doi.org/10.18273/revion.v38n3-2025005

Derechos de autor 2025 Wilfrethd Andrés Suárez Trujillo, Claudia Yolanda Reyes

Creative Commons License

Esta obra está bajo una licencia internacional Creative Commons Atribución-SinDerivadas 4.0.

Resumen

El artículo de revisión expone las propiedades de los flavonoides presentes en la Ortiga (Urtica dioica sp) y el salicilato de metilo (MeSal) para la formulación de una crema de uso tópico, basándose en las propiedades antiinflamatorias, antioxidantes, antimicrobianas y analgésicas de dichos compuestos, verificando así su posible sinergia. El objetivo fue evaluar desde una perspectiva teórica, el potencial de estos componentes para aliviar dolores musculares e inflamaciones cutáneas. La metodología incluyó una búsqueda sistemática, donde se consultaron bases de datos como Scopus, SpringerLink, MDPI y Google Scholar, buscando artículos de investigación, revisión y libros. Ahora bien, la U. dioica sp se le atribuyen propiedades gracias a los flavonoides y a los compuestos fenólicos que contiene, haciéndola útil contra problemas como la artritis y las alergias. Por otra parte, el MeSal es eficaz y muy utilizado en tratamientos dermatológicos ya que, debido a su acción analgésica y antiinflamatoria, penetra en la piel y reduce la inflamación sin generar efectos adversos, haciéndolo un compuesto ideal en la formulación de cremas tópicas. De lo anterior se concluye desde una perspectiva teórica, que la formulación de una crema tópica que presente las propiedades de la U. dioica y el MeSal puede ofrecer una solución alternativa y eficaz contra el tratamiento de afecciones cutáneas y musculares, sin embargo, se recomienda realizar ensayos experimentales que aporten al ámbito terapéutico natural para la formulación de dicha crema.

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  1. [1] Vidal M, Roldán T. Capacidad de penetración y efecto antiinflamatorio local de un gel de salicilato de metilo con esencia de trementina, alcanfor y mentol para el tratamiento local sintomático de dolores musculares y articulares. Farm. Comunitarios. 2024;16(3):5-11. https://doi.org/10.33620/FC.2173-9218.(2024).15
  2. [2] Malhotra R, Husain A, Ahmad F, Rakhra G. Role of flavonoids as anti-inflammatory agents in inflammatory diseases. PharmaNutrition. 2026;35:100464. https://doi.org/10.1016/j.phanu.2025.100464
  3. [3] Baqer SH, Al-Shawi SG, Al-Younis ZK. Quercetin, the Potential Powerful Flavonoid for Human and Food: A Review. Front Biosci. (Elite Ed). 2024;16(3):30. https://doi.org/10.31083/j.fbe1603030
  4. [4] Abi Sleiman M, Younes M, Hajj R, Salameh T, Abi Rached S, Abi Younes R, et al. Urtica dioica: Anticancer Properties and Other Systemic Health Benefits from In Vitro to Clinical Trials. Int. J. Mol. Sci. 2024;25(13):7501; https://doi.org/10.3390/ijms25137501
  5. [5] Devkota HP, Paudel KR, Khanal S, Baral A, Panth N, Adhikari-Devkota A, et al. Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties. Molecules. 2022;27(16):5219; https://doi.org/10.3390/molecules27165219
  6. [6] Carvalho AR, Costa G, Figueirinha A, Liberal J, Prior JAV, Lopes MC, et al. Urtica spp.: Phenolic composition, safety, antioxidant and anti-inflammatory activities. Food Res. Int. 2017;99(1):485–94. https://doi.org/10.1016/j.foodres.2017.06.008
  7. [7] Grauso L, de Falco B, Lanzotti V, Motti R. Stinging nettle, Urtica dioica L.: botanical, phytochemical and pharmacological overview. Phytochem. Rev. 2020;19:1341–1377. https://doi.org/10.1007/s11101-020-09680-x
  8. [8] Jan KN, zarafshan K, Singh S. Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great functional potential. Food Measure. 2017;11(2):423–33. https://doi.org/10.1007/s11694-016-9410-4
  9. [9] Aksoylu Özbek Z, Kawata K, Zhou H, Chung C, Park JH, McClements DJ. Isolation and characterization of nettle (Urtica dioica L.) seed proteins: Conversion of underutilized by-products of the edible oil industry into food emulsifiers. Food Chem. 2024;456:139878. https://doi.org/10.1016/j.foodchem.2024.139878
  10. [10] Nabavi SM, Šamec D, Tomczyk M, Milella L, Russo D, Habtemariam S, et al. Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering. Biotechnol. Adv. 2020;38:107316. https://doi.org/10.1016/j.biotechadv.2018.11.005
  11. [11] Farag MA, Weigend M, Luebert F, Brokamp G, Wessjohann LA. Phytochemical, phylogenetic, and anti-inflammatory evaluation of 43 Urtica accessions (stinging nettle) based on UPLC-Q-TOFMS metabolomic profiles. Phytochemistry. 2013;96:170–83. https://doi.org/10.1016/j.phytochem.2013.09.016
  12. [12] Di Virgilio N, Papazoglou EG, Jankauskiene Z, Di Lonardo S, Praczyk M, Wielgusz K. The potential of stinging nettle (Urtica dioica L.) as a crop with multiple uses. Ind Crops Prod. 2015;68:42–9. https://doi.org/10.1016/j.indcrop.2014.08.012
  13. [13] Bouazizi A, Felfoul I, Attia H, Karoui R. Characterization of nettle leaves (Urtica dioica) as a novel source of protease for clotting dromedary milk by non-destructive methods. Colloids Surf B: Biointerfaces. 2022;211:112312. https://doi.org/10.1016/j.colsurfb.2021.112312
  14. [14] Kronbauer M, Shorstkii I, Botelho da Silva S, Toepfl S, Lammerskitten A, Siemer C. Pulsed electric field assisted extraction of soluble proteins from nettle leaves (Urtica dioica L.): kinetics and optimization using temperature and specific energy. Sustain. Food Technol. 2023;1(6):886–95. https://doi.org/10.1039/d3fb00053b
  15. [15] Đurović S, Kojić I, Radić D, Smyatskaya YA, Bazarnova JG, Filip S, et al. Chemical Constituents of Stinging Nettle (Urtica dioica L.): A Comprehensive Review on Phenolic and Polyphenolic Compounds and Their Bioactivity. Int. J. Mol. Sci. 2024;25(6):3430. https://doi.org/10.3390/ijms25063430
  16. [16] Durović S, Zeković Z, Šorgić S, Popov S, Vujanović M, Radojković M. Fatty acid profile of stinging nettle leaves: Application of modern analytical procedures for sample preparation and analysis. Anal. Methods. 2018;10(9):1080–7. https://doi.org/10.1039/C7AY02559A
  17. [17] Đurović S, Micić D, Šorgić S, Popov S, Gašić U, Tosti T, et al. Recovery of Polyphenolic Compounds and Vitamins from the Stinging Nettle Leaves: Thermal and Behavior and Biological Activity of Obtained Extracts. Molecules. 2023;28(5):2278. https://doi.org/10.3390/molecules28052278
  18. [18] Konieczynski P, Lysiuk R, Wesolowski M. Total flavonoid and ionic elements contents in 32 medicinal plants collected from natural habitats in Northern Ukraine. J. Herb. Med. 2021;29(November 2020):100492. https://doi.org/10.1016/j.hermed.2021.100492
  19. [19] Parente R, Paiva-Santos AC, Cabral C, Costa G. Comprehensive review of Urtica dioica L. (Urticaceae) phytochemistry and anti-inflammatory properties. Phytochem Rev 2025;24:1591–1628. https://doi.org/10.1007/s11101-024-09980-6
  20. [20] Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167; https://doi.org/10.3390/nu8030167
  21. [21] Flórez M, Cazón P, Vázquez M. Characterization of active films of chitosan containing nettle Urtica dioica L. extract: Spectral and water properties, microstructure, and antioxidant activity. Int. J. Biol. Macromol. 2023;253(6):127318 https://doi.org/10.1016/j.ijbiomac.2023.127318
  22. [22] Đurović S, Pezo L, Gašić U, Gorjanović S, Pastor F, Bazarnova JG, et al. Recovery of Biologically Active Compounds from Stinging Nettle Leaves Part II: Processing of Exhausted Plant Material after Supercritical Fluid Extraction. Foods. 2023;12(4):809. https://doi.org/10.3390/foods12040809
  23. [23] Zhao Y, Chen B, Shen J, Wan L, Zhu Y, Yi T, et al. The Beneficial Effects of Quercetin, Curcumin, and Resveratrol in Obesity. Oxid Med Cell Longev. 2017;2017:1459497. https://doi.org/10.1155/2017/1459497
  24. [24] Fan S, Raychaudhuri S, Ogedengbe O, Mochama V, Obanda DN. Impacts of the vegetable Urtica dioica on the intestinal T and B cell phenotype and macronutrient absorption in C57BL/6J mice with diet-induced obesity. J. Nutr. Biochem. 2024;129:109634. https://doi.org/10.1016/j.jnutbio.2024.109634
  25. [25] Wujiamaiti Z, Kizaibek M, Bahetijian D, Li Y, Gui Y, Abula A. Urtica cannabina L. water extract exhibits anti-inflammatory activity by regulating inflammatory cytokines: In vitro and in vivo evidence. J. Ethnopharmacol. 2024;318(PA):116907. https://doi.org/10.1016/j.jep.2023.116907
  26. [26] Mzid M, Ben Khedir S, Bardaa S, Sahnoun Z, Rebai T. Chemical composition, phytochemical constituents, antioxidant and anti-inflammatory activities of Urtica urens L. leaves. Arch. Physio.l Biochem. 2017;123(2):93–104. https://doi.org/10.1080/13813455.2016.1255899
  27. [27] Ghiyasi Y, Salahi E, Esfahani H. Synergy effect of Urtica dioica and ZnO NPs on microstructure, antibacterial activity and cytotoxicity of electrospun PCL scaffold for wound dressing application. Mater. Today Commun. 2021;26:102163. https://doi.org/10.1016/j.mtcomm.2021.102163
  28. [28] Balpetek Külcü D, Demir Gökışık C, Aydın S. An Investigation of Antibacterial and Antioxidant Activity of Nettle (Urtica dioica L.), Mint (Mentha piperita), Thyme (Thyme serpyllum) and Chenopodium album L. Plants from Yaylacık Plateau, Giresun, Turkey. Turkish JAF Sci. Tech. 2019;7(1):73-80. https://doi.org/10.24925/turjaf.v7i1.73-80.2123
  29. [29] Ahmadpourmir H, Attar H, Asili J, Soheili V, Taghizadeh SF, Shakeri A. Natural-derived acetophenones: chemistry and pharmacological activities. Nat. Prod. Bioprospect. 2024;14:28. https://doi.org/10.1007/s13659-024-00447-x
  30. [30] Khan MZ, Azad AK, Jan S, Safdar M, Bibi S, Majid AMSA, et al. An Experimental and Computational Analysis of Plant Compounds from Whole Urtica dioica L. Plant’s Essential Oil for Antioxidant and Antibacterial Activities. Metabolites. 2023;13(4):502. https://doi.org/10.3390/metabo13040502
  31. [31] Semwal P, Rauf A, Olatunde A, Singh P, Zaky MY, Islam MM, et al. The medicinal chemistry of Urtica dioica L.: from preliminary evidence to clinical studies supporting its neuroprotective activity. Nat. Prod. Bioprospect. 2023;13:16. https://doi.org/10.1007/s13659-023-00380-5
  32. [32] Mhalhel K, Kadmi Y, Ben Chira A, Levanti M, Pansera L, Cometa M, et al. Urtica dioica Extract Abrogates Chlorpyrifos-Induced Toxicity in Zebrafish Larvae. Int. J. Mol. Sci. 2024;25(12):6631. https://doi.org/10.3390/ijms25126631
  33. [33] Kılıç CS. Rheum ribes L. Novel Drug Targets with Traditional Herbal Medicines: Scientific and Clinical Evidence. Springer Cham; 2022. p. 495–512. https://doi.org/10.1007/978-3-031-07753-1
  34. [34] Bhusal KK, Magar SK, Thapa R, Lamsal A, Bhandari S, Maharjan R, et al. Nutritional and pharmacological importance of stinging nettle (Urtica dioica L.): A review. Heliyon. 2022;8(6):e09717. https://doi.org/10.1016/j.heliyon.2022.e09717
  35. [35] Chauhan S, Thayes C, Ali B, Rawal YK. Evaluation of Himalayan nettle (Urtica ardens) extract meal in common carp (Cyprinus carpio) feed: Impact on growth performance, digestive enzyme activity and antioxidant capacity. Aquac. Rep. 2024;36:102142. https://doi.org/10.1016/j.aqrep.2024.102142
  36. [36] Abd-Nikfarjam B, Abbasi M, Memarzadeh M, Farzam SA, Jamshidian A, Dolati-Somarin A. Therapeutic efficacy of Urtica dioica and evening primrose in patients with rheumatoid arthritis: A randomized double-blind, placebo-controlled clinical trial. J. Herb. Med. 2022;32:100556. https://doi.org/10.1016/j.hermed.2022.100556
  37. [37] Mitrović J, Nikolić N, Karabegović I, Savić S, Petrović S, Pešić M, et al. Evaluation of the solvent effect on the extraction and antioxidant activity of phenolic compounds from the nettle (Urtica dioica L.) seeds: application of PCA and regression analyses. Food Measure. 2024;18(8):6618–26. https://doi.org/10.1007/s11694-024-02675-8
  38. [38] Mohammed DM, Maan SA, Abou Baker DH, Abozed SS. In vitro assessments of antioxidant, antimicrobial, cytotoxicity and anti-inflammatory characteristics of flavonoid fractions from flavedo and albedo orange peel as novel food additives. Food Biosci. 2024;62:105581. https://doi.org/10.1016/j.fbio.2024.105581
  39. [39] Brodowska KM. Natural flavonoids: classification, potential role, and application of flavonoid analogues. Eur. J. Biol. Res. 2017;7(2):108–23. https://doi.org/10.5281/zenodo.545778
  40. [40] Filip D, Macocinschi D, Nica SL, Condurache B, Stoleru E, Mihaela D, et al. Hybrid green bionanocomposites based on chitosan/starch/gelatin and metallic nanoparticles for biological applications. Int. J. Biol. Macromol. 2023;127571. https://doi.org/10.1016/j.ijbiomac.2023.127571
  41. [41] Karg CA, Doppler C, Schilling C, Jakobs F, Dal Colle MCS, Frey N, et al. A yellow chlorophyll catabolite in leaves of Urtica dioica L.: An overlooked phytochemical that contributes to health benefits of stinging nettle. Food Chem.
  42. 2021;359:129906. https://doi.org/10.1016/j.foodchem.2021.129906
  43. [42] Wang J, Zhao X, Chen J, Li X, Hao D, Li T, et al. Efficacy and mechanism of methyl salicylate in the enhancement of skin delivery of herbal medicines. J. Tradit. Chin. Med. 2021;8(4):336–42. https://doi.org/10.1016/j.jtcms.2021.09.001
  44. [43] Amil MA, Gan KZ, Mohamad Adzib MS, Bujang NB, Mohd Yusop AY, Md Roduan MR. GC–MS method for routine analysis of camphor, menthol, methyl salicylate, and thymol in traditional topical products: Addressing compliance and adulteration from Malaysia’s National Pharmaceutical Regulatory Agency. Results Chem. 2025;18:102721. https://doi.org/10.1016/j.rechem.2025.102721
  45. [44] Ashrafi AM, Bytešníková Z, Cané C, Richtera L, Vallejos S. New trends in methyl salicylate sensing and their implications in agriculture. Biosens. Bioelectron. 2023;223:115008. https://doi.org/10.1016/j.bios.2022.115008
  46. [45] Li X, Zhang LP, Zhang L, Yan P, Ahammed GJ, Han WY. Methyl salicylate enhances flavonoid biosynthesis in tea leaves by stimulating the phenylpropanoid pathway. Molecules. 2019;24(2):362. https://doi.org/10.3390/molecules24020362
  47. [46] Singewar K, Fladung M, Robischon M. Methyl salicylate as a signaling compound that contributes to forest ecosystem stability. Trees. 2021;35(6):1755–69. https://doi.org/10.1007/s00468-021-02191-y
  48. [47] Gondor OK, Pál M, Janda T, Szalai G. The role of methyl salicylate in plant growth under stress conditions. J. Plant. Physiol. 2022;277:153809. https://doi.org/10.1016/j.jplph.2022.153809
  49. [48] Chen L, Wang WS, Wang T, Meng XF, Chen TT, Huang XX, et al. Methyl salicylate glucosylation regulates plant defense signaling and systemic acquired resistance. Plant Physiol. 2019;180(4):2167–81. https://doi.org/10.1104/pp.19.00091
  50. [49] Mao P, Liu Z, Xie M, Jiang R, Liu W, Wang X, et al. Naturally Occurring Methyl Salicylate Glycosides. Mini Rev. Med. Chem. 2014;14(1)56–63. https://doi.org/10.2174/1389557513666131211110004
  51. [50] Kalaivani K, Kalaiselvi MM, Senthil-Nathan S. Effect of methyl salicylate (MeSA), an elicitor on growth, physiology and pathology of resistant and susceptible rice varieties. Sci. Rep. 2016;6:34498. https://doi.org/10.1038/srep34498
  52. [51] Gacnik S, Veberič R, Hudina M, Marinovic S, Halbwirth H, Mikulič‐petkovšek M. Salicylic and methyl salicylic acid affect quality and phenolic profile of apple fruits three weeks before the harvest. Plants. 2021;10(9):1807. https://doi.org/10.3390/plants10091807
  53. [52] Mei J, Li X, You Y, Fan X, Sun C, Guo F, et al. Methyl salicylate affects fruit quality and aroma compounds of cherry during cold storage. Sci. Hortic. 2024;333:113291. https://doi.org/10.1016/j.scienta.2024.113291
  54. [53] Gacnik S, Veberic R, Marinovic S, Halbwirth H, Mikulic-Petkovsek M. Effect of pre-harvest treatments with salicylic and methyl salicylic acid on the chemical profile and activity of some phenylpropanoid pathway related enzymes in apple leaves. Sci Hortic. 2021;277(October 2020):109794. https://doi.org/10.1016/j.scienta.2020.109794
  55. [54] Agurla S, Sunitha V, Raghavendra AS. Methyl salicylate is the most effective natural salicylic acid ester to close stomata while raising reactive oxygen species and nitric oxide in Arabidopsis guard cells. Plant Physiol. Biochem. 2020;157:276–83. https://doi.org/10.1016/j.plaphy.2020.10.026
  56. [55] Ojha PK, Poudel DK, Dangol S, Rokaya A, Timsina S, Satyal P, et al. Volatile Constituent Analysis of Wintergreen Essential Oil and Comparison with Synthetic Methyl Salicylate for Authentication. Plants. 2022;11(8):1090. https://doi.org/10.3390/plants11081090
  57. [56] Gębka N, Adamczyk J, Gębka-Kępińska B, Mizgała-Izworska E. The role of flavonoids in prevention and treatment of selected skin diseases. J. Pre Clin. Clin. Res. 2022;16(3):99–107. https://doi.org/10.26444/jpccr/152551
  58. [57] Alizadeh K, Esmaeili R, Shorofi SA, Mousavinasab N, Espahbodi F, Esmaeili M. Effect of Urtica dioica (nettle) on quality of sleep in hemodialysis patients: A randomized clinical trial. J. Herb. Med. 2021;28:100356. https://doi.org/10.1016/j.hermed.2020.100356
  59. [58] Loshali A, Joshi BC, Sundriyal A, Uniyal S. Antiepileptic effects of antioxidant potent extract from Urtica dioica Linn. root on pentylenetetrazole and maximal electroshock induced seizure models. Heliyon. 2021;7(2):e06195. https://doi.org/10.1016/j.heliyon.2021.e06195
  60. [59] Engelhardt L, Pöhnl T, Neugart S. Edible Wild Vegetables Urtica dioica L. and Aegopodium podagraria L.–Antioxidants Affected by Processing. Plants. 2022;11(20):2710. https://doi.org/10.3390/plants11202710
  61. [60] Brahmi-Chendouh N, Piccolella S, Nigro E, Hamri-Zeghichi S, Madani K, Daniele A, et al. Urtica dioica L. leaf chemical composition: A never-ending disclosure by means of HRMS/MS techniques. J. Pharm. Biomed. Anal. 2021;195:113892. https://doi.org/10.1016/j.jpba.2021.11389
  62. [61] Cuinica LG, Macêdo RO. Thermoanalytical characterization of plant drug and extract of Urtica dioica L. and kinetic parameters analysis. J. Therm. Anal. Calorim. 2018;133(1):591–602. https://doi.org/10.1007/s10973-018-6986-4
  63. [62] Flórez M, Cazón P, Vázquez M. Antioxidant Extracts of Nettle (Urtica dioica) Leaves: Evaluation of Extraction Techniques and Solvents. Molecules. 2022;27(18):6015. https://doi.org/10.3390/molecules27186015
  64. [63] Upton R. Stinging nettles leaf (Urtica dioica L.): Extraordinary vegetable medicine. J. Herb. Med. 2013;3(1):9–38. https://doi. org/10.1016/j.hermed.2012.11.001
  65. [64] Safar VZ, Ngugi MP, Orinda G, Njagi EM. Anti-pyretic, Anti-inflammatory and Analgesic Activities of Aqueous Leaf Extract of Urtica Dioica (L.) in Albino Mice. Med. Aromat. Plants. 2016;05(02):237. https://doi.org/10.4172/2167-0412.1000237
  66. [65] Yeoh SC, Loh PL, Murugaiyah V, Goh CF. Development and Characterisation of a Topical Methyl Salicylate Patch: Effect of Solvents on Adhesion and Skin Permeation. Pharmaceutics. 2022;14(11):2491. https://doi.org/10.3390/pharmaceutics14112491
  67. [66] Telaprolu KC, Grice JE, Mohammed YH, Roberts MS. Human Skin Drug Metabolism: Relationships between Methyl Salicylate Metabolism and Esterase Activities in IVPT Skin Membranes. Metabolites. 2023;13(8):934. https://doi.org/10.3390/metabo13080934
  68. [67] Al-Tameme HJ, Hadi MY, Hameed IH. Phytochemical analysis of Urtica dioica leaves by fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry. J. Pharmacognosy Phytother. 2015;7(10):238–52. https://doi.org/10.5897/JPP2015.0361
  69. [68] Alimoddin M, Jayakumari S, Fatima B, Hasan N, Ali S, Sami F, et al. Pharmacological applications of Urtica dioica: a comprehensive review of its traditional use and modern scientific evidence. J. Herb. Med. 2024;48:100935. https://doi.org/10.1016/j.hermed.2024.100935
  70. [69] Dhouibi R, Affes H, Ben Salem M, Hammami S, Sahnoun Z, Zeghal KM, et al. Screening of pharmacological uses of Urtica dioica and others benefits. Prog. Biophys. Mol. Biol. 2020;150:67–77. https://doi.org/10.1016/j.pbiomolbio.2019.05.008
  71. [70] Baumgardner DJ. Stinging Nettle: the Bad, the Good, the Unknown. J. Patient Cent. Res. Rev. 2016;3(1):48–53. https://doi.org/10.17294/2330-0698.1216