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Current Drug Delivery

Author(s): Marzia Vasarri, Linda Ponti, Donatella Degl'Innocenti and Maria Camilla Bergonzi*

DOI: 10.2174/1567201820666230111112415

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Liposomal Formulation Improves the Bioactivity of Usnic Acid in RAW 264.7 Macrophage Cells Reducing its Toxicity

Page: [91 - 103] Pages: 13

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Abstract

Background: Reactive oxygen species (ROS) production and oxidative stress may be responsible for the onset of several chronic diseases. Usnic acid (UA) is a natural secondary metabolite of lichens with several healthful bioactivities, including antioxidant properties. However, UA is a hydrophobic compound known for its hepatic toxicity. These aspects limit its therapeutic applications. To overcome these drawbacks and improve the pharmacological use of hydrophobic compounds, nanotechnology is widely used. Therefore, the incorporation of UA into appropriate nanocarriers could enhance the bioactivity of UA by increasing its solubility.

Objective: The aim of this work was to improve the solubility of UA and its bioactivity in the absence of cytotoxicity.

Methods: In this study, UA loaded liposomes (UA-LP) were developed. The formulations were chemically and physically characterized, and an in vitro release study was performed. Free UA and UA-LP were tested on RAW 264.7 murine macrophages in terms of cytotoxicity, intracellular ROS production, and NO release in the absence or presence of pro-oxidant LPS stimulus.

Results: UA-LP showed excellent physical and chemical stability during storage and improved solubility of UA. UA-LP showed an antioxidant effect in the absence of cytotoxicity compared with free UA on LPS-exposed macrophages.

Conclusion: For the first time, liposomal formulation improved the beneficial action of UA in terms of solubility and antioxidant activity.

Graphical Abstract

[1]
Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS sources in physiological and pathological conditions. Oxid. Med. Cell. Longev., 2016, 2016, 1-44.
[http://dx.doi.org/10.1155/2016/1245049] [PMID: 27478531]
[2]
Sharifi-Rad, M.; Anil Kumar, N.V.; Zucca, P.; Varoni, E.M.; Dini, L.; Panzarini, E.; Rajkovic, J.; Tsouh Fokou, P.V.; Azzini, E.; Peluso, I.; Prakash Mishra, A.; Nigam, M.; El Rayess, Y.; Beyrouthy, M.E.; Polito, L.; Iriti, M.; Martins, N.; Martorell, M.; Docea, A.O.; Setzer, W.N.; Calina, D.; Cho, W.C.; Sharifi-Rad, J. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front. Physiol., 2020, 11, 694.
[http://dx.doi.org/10.3389/fphys.2020.00694] [PMID: 32714204]
[3]
Chelombitko, M.A. Role of reactive oxygen species in inflammation: A minireview. Moscow Univ. Biol. Sci. Bull., 2018, 73(4), 199-202.
[http://dx.doi.org/10.3103/S009639251804003X]
[4]
García-Sánchez, A.; Miranda-Díaz, A.G.; Cardona-Muñoz, E.G. The role of oxidative stress in physiopathology and pharmacological treatment with pro- and antioxidant properties in chronic diseases. Oxid. Med. Cell. Longev., 2020, 2020, 1-16.
[http://dx.doi.org/10.1155/2020/2082145] [PMID: 32774665]
[5]
Zhao, Y.; Wang, M.; Xu, B. A comprehensive review on secondary metabolites and health-promoting effects of edible lichen. J. Funct. Foods, 2021, 80, 104283.
[http://dx.doi.org/10.1016/j.jff.2020.104283]
[6]
González-Burgos, E.; Fernández-Moriano, C.; Gómez-Serranillos, M.P. Current knowledge on Parmelia genus: Ecological interest, phytochemistry, biological activities and therapeutic potential. Phytochemistry, 2019, 165, 112051.
[http://dx.doi.org/10.1016/j.phytochem.2019.112051] [PMID: 31234093]
[7]
Shukla, V.; Joshi, G.P.; Rawat, M.S.M. Lichens as a potential natural source of bioactive compounds: A review. Phytochem. Rev., 2010, 9(2), 303-314.
[http://dx.doi.org/10.1007/s11101-010-9189-6]
[8]
Ingólfsdóttir, K.; Bloomfield, S.F.; Hylands, P.J. in vitro evaluation of the antimicrobial activity of lichen metabolites as potential preservatives. Antimicrob. Agents Chemother., 1985, 28(2), 289-292.
[http://dx.doi.org/10.1128/AAC.28.2.289] [PMID: 3834834]
[9]
Galanty, A. Paśko, P.; Podolak, I. Enantioselective activity of usnic acid: A comprehensive review and future perspectives. Phytochem. Rev., 2019, 18(2), 527-548.
[http://dx.doi.org/10.1007/s11101-019-09605-3]
[10]
Ingólfsdóttir, K. Usnic acid. Phytochemistry, 2002, 61(7), 729-736.
[http://dx.doi.org/10.1016/S0031-9422(02)00383-7] [PMID: 12453567]
[11]
Araújo, A.A.S.; de Melo, M.G.D.; Rabelo, T.K.; Nunes, P.S.; Santos, S.L.; Serafini, M.R.; Santos, M.R.V.; Quintans-Júnior, L.J.; Gelain, D.P. Review of the biological properties and toxicity of usnic acid. Nat. Prod. Res., 2015, 29(23), 2167-2180.
[http://dx.doi.org/10.1080/14786419.2015.1007455] [PMID: 25707417]
[12]
Pramyothin, P.; Janthasoot, W.; Pongnimitprasert, N.; Phrukudom, S.; Ruangrungsi, N. Hepatotoxic effect of (+)usnic acid from Usnea siamensis Wainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria. J. Ethnopharmacol., 2004, 90(2-3), 381-387.
[http://dx.doi.org/10.1016/j.jep.2003.10.019] [PMID: 15013205]
[13]
Chitturi, S.; Farrell, G.C. Hepatotoxic slimming aids and other herbal hepatotoxins. J. Gastroenterol. Hepatol., 2008, 23(3), 366-373.
[http://dx.doi.org/10.1111/j.1440-1746.2008.05310.x] [PMID: 18318821]
[14]
Foti, R.S.; Dickmann, L.J.; Davis, J.A.; Greene, R.J.; Hill, J.J.; Howard, M.L.; Pearson, J.T.; Rock, D.A.; Tay, J.C.; Wahlstrom, J.L.; Slatter, J.G. Metabolism and related human risk factors for hepatic damage by usnic acid containing nutritional supplements. Xenobiotica, 2008, 38(3), 264-280.
[http://dx.doi.org/10.1080/00498250701802514] [PMID: 18274956]
[15]
Sanchez, W.; Maple, J.T.; Burgart, L.J.; Kamath, P.S. Severe hepatotoxicity associated with use of a dietary supplement containing usnic acid. Mayo Clin. Proc., 2006, 81(4), 541-544.
[http://dx.doi.org/10.4065/81.4.541] [PMID: 16610575]
[16]
Neff, G.W.; Rajender Reddy, K.; Durazo, F.A.; Meyer, D.; Marrero, R.; Kaplowitz, N. Severe hepatotoxicity associated with the use of weight loss diet supplements containing Ma Huang or Usnic acid. J. Hepatol., 2004, 41(6), 1062-1064.
[http://dx.doi.org/10.1016/j.jhep.2004.06.028] [PMID: 15582145]
[17]
Kwong, S.P.; Wang, C. Review: Usnic acid-induced hepatotoxicity and cell death. Environ. Toxicol. Pharmacol., 2020, 80, 103493.
[http://dx.doi.org/10.1016/j.etap.2020.103493] [PMID: 32961280]
[18]
Lukáč M.; Prokipčák, I.; Lacko, I.; Devínsky, F. Solubilisation of (+)-usnic acid in aqueous micellar solutions of gemini and heterogemini surfactants and their equimolar mixture. Acta Fac. Pharm. Univ. Comen., 2012, 59(2), 36-43.
[http://dx.doi.org/10.2478/v10219-012-0022-8]
[19]
Müller, K. Pharmaceutically relevant metabolites from lichens. Appl. Microbiol. Biotechnol., 2001, 56(1-2), 9-16.
[http://dx.doi.org/10.1007/s002530100684] [PMID: 11499952]
[20]
Kristmundsdóttir, T.; Jónsdóttir, E.; Ögmundsdóttir, H.M.; Ingólfsdóttir, K. Solubilization of poorly soluble lichen metabolites for biological testing on cell lines. Eur. J. Pharm. Sci., 2005, 24(5), 539-543.
[http://dx.doi.org/10.1016/j.ejps.2005.01.011] [PMID: 15784343]
[21]
Jin, J.; Rao, Y.; Bian, X.; Zeng, A.; Yang, G. Solubility of (+)-usnic acid in water, ethanol, acetone, ethyl acetate and n-hexane. J. Solution Chem., 2013, 42(5), 1018-1027.
[http://dx.doi.org/10.1007/s10953-013-0010-1]
[22]
Bilia, A.R.; Piazzini, V.; Bergonzi, M.C. Nanotechnology Applications for Natural Products Delivery. In: Sustainable Agriculture Reviews 44. Sustainable Agriculture Reviews, vol 44. Springer, Cham; Saneja, A.; Panda, A.; Lichtfouse, E., Eds.; 1-46.
[http://dx.doi.org/10.1007/978-3-030-41842-7_1]
[23]
Patra, J.K.; Das, G.; Fraceto, L.F.; Campos, E.V.R.; Rodriguez-Torres, M.P.; Acosta-Torres, L.S.; Diaz-Torres, L.A.; Grillo, R.; Swamy, M.K.; Sharma, S.; Habtemariam, S.; Shin, H.S. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnology, 2018, 16(1), 71.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[24]
Zugic, A.; Tadic, V.; Savic, S. Nano- and microcarriers as drug delivery systems for usnic acid: Review of literature. Pharmaceutics, 2020, 12(2), 156.
[http://dx.doi.org/10.3390/pharmaceutics12020156] [PMID: 32075296]
[25]
da Silva Santos, N.P.; Nascimento, S.C.; Wanderley, M.S.O.; Pontes-Filho, N.T.; da Silva, J.F.; de Castro, C.M.M.B.; Pereira, E.C.; da Silva, N.H.; Honda, N.K.; Santos-Magalhães, N.S. Nanoencapsulation of usnic acid: An attempt to improve antitumour activity and reduce hepatotoxicity. Eur. J. Pharm. Biopharm., 2006, 64(2), 154-160.
[http://dx.doi.org/10.1016/j.ejpb.2006.05.018] [PMID: 16899355]
[26]
Lira, M.C.B.; Ferraz, M.S.; Silva, D.G.V.C.; Cortes, M.E.; Teixeira, K.I.; Caetano, N.P.; Sinisterra, R.D.; Ponchel, G.; Santos-Magalhães, N.S. Inclusion complex of usnic acid with β-cyclodextrin: Characterization and nanoencapsulation into liposomes. J. Incl. Phenom. Macrocycl. Chem., 2009, 64(3-4), 215-224.
[http://dx.doi.org/10.1007/s10847-009-9554-5]
[27]
dos Santos, P.H.; Mesquita, T.; Miguel-dos-Santos, R.; de Almeida, G.K.M.; de Sá, L.A.; dos Passos Menezes, P.; de Souza Araujo, A.A.; Lauton-Santos, S. Inclusion complex with β-cyclodextrin is a key determining factor for the cardioprotection induced by usnic acid. Chem. Biol. Interact., 2020, 332, 109297.
[http://dx.doi.org/10.1016/j.cbi.2020.109297] [PMID: 33096055]
[28]
Mukerjee, A.; Pandey, H.; Tripathi, A.K.; Singh, S.K. Development, characterization and evaluation of cinnamon oil and usnic acid blended nanoemulsion to attenuate skin carcinogenicity in swiss albino mice. Biocatal. Agric. Biotechnol., 2019, 20, 101227.
[http://dx.doi.org/10.1016/j.bcab.2019.101227]
[29]
Nascimento Porto Neto, A.; Santos Cruz, C.F.; Serafini, M.R.; dos Passos Menezes, P.; de Carvalho, Y.M.B.G.; Matos, C.R.S.; Nunes, P.S.; Cardoso, J.C.; de Albuquerque Júnior, R.L.C.; Rolim Neto, P.J.; Silva, F.A.; de Souza Araújo, A.A. Usnic acid-incorporated alginate and gelatin sponges prepared by freeze-drying for biomedical applications. J. Therm. Anal. Calorim., 2017, 127(2), 1707-1713.
[http://dx.doi.org/10.1007/s10973-016-5760-8]
[30]
Santos, N.P.; Nascimento, S.C.; Silva, J.F.; Pereira, E.C.G.; Silva, N.H.; Honda, N.K.; Santos-Magalhães, N.S. Usnic acid-loaded nanocapsules: An evaluation of cytotoxicity. J. Drug Deliv. Sci. Technol., 2005, 15(5), 355-361.
[http://dx.doi.org/10.1016/S1773-2247(05)50065-0]
[31]
Garg, A.; Garg, S.; Sahu, N.K.; Rani, S.; Gupta, U.; Yadav, A.K. Heparin appended ADH-anionic polysaccharide nanoparticles for site-specific delivery of usnic acid. Int. J. Pharm., 2019, 557, 238-253.
[http://dx.doi.org/10.1016/j.ijpharm.2018.12.049] [PMID: 30594688]
[32]
Barbosa, J.A.P.; Franco, E.S.; Silva, C.V.N.S.; Bezerra, T.O.; Santana, M.A.N.; Júnior, C.H.R.C.; Silva, T.G.; Santos, N.P.S.; Maia, M.B.S. Poly-ε-caprolactone microsphere polymers containing usnic acid: Acute toxicity and anti-inflammatory activity. Evid.-. Evid. Based Complement. Alternat. Med., 2017, 2017, 1-9.
[http://dx.doi.org/10.1155/2017/7392891] [PMID: 29348773]
[33]
Martinelli, A.; Bakry, A.; D’Ilario, L.; Francolini, I.; Piozzi, A.; Taresco, V. Release behavior and antibiofilm activity of usnic acid-loaded carboxylated poly(l-lactide) microparticles. Eur. J. Pharm. Biopharm., 2014, 88(2), 415-423.
[http://dx.doi.org/10.1016/j.ejpb.2014.06.002] [PMID: 24929210]
[34]
Grumezescu, V.; Holban, A.M.; Grumezescu, A.M.; Socol, G.; Ficai, A.; Vasile, B.S. Truscă R.; Bleotu, C.; Lazar, V.; Chifiriuc, C.M.; Mogosanu, G.D. Usnic acid-loaded biocompatible magnetic PLGA-PVA microsphere thin films fabricated by MAPLE with increased resistance to staphylococcal colonization. Biofabrication, 2014, 6(3), 035002.
[http://dx.doi.org/10.1088/1758-5082/6/3/035002] [PMID: 24722318]
[35]
Grumezescu, A.M.; Cotar, A.I.; Andronescu, E.; Ficai, A.; Ghitulica, C.D.; Grumezescu, V.; Vasile, B.S.; Chifiriuc, M.C. In vitro activity of the new water-dispersible Fe3O4@usnic acid nanostructure against planktonic and sessile bacterial cells. J. Nanopart. Res., 2013, 15(7), 1766-1776.
[http://dx.doi.org/10.1007/s11051-013-1766-3]
[36]
Holban, A.M.; Grumezescu, A.M.; Andronescu, E.; Grumezescu, V.; Chifiriuc, C.M.; Radulescu, R. Magnetite-usnic acid nanostructured bioactive material with antimicrobial activity. Rev. Rom. Mater., 2013, 43, 402-407.
[37]
Alpsoy, L.; Baykal, A.; Amir, M.; Ülker, Z.; Nawaz, M. SPION@APTES@FA-PEG@usnic acid bionanodrug for cancer therapy. J. Supercond. Nov. Magn., 2018, 31(5), 1395-1401.
[http://dx.doi.org/10.1007/s10948-017-4333-9]
[38]
Subramanian, P. Lipid-based nanocarrier system for the effective delivery of nutraceuticals. Molecules, 2021, 26(18), 5510.
[http://dx.doi.org/10.3390/molecules26185510] [PMID: 34576981]
[39]
Lira, M.C.B.; Siqueira-Moura, M.P.; Rolim-Santos, H.M.L.; Galetti, F.C.S.; Simioni, A.R.; Santos, N.P.; Tabosa Do Egito, E.S.; Silva, C.L.; Tedesco, A.C.; Santos-Magalhães, N.S. in vitro uptake and antimycobacterial activity of liposomal usnic acid formulation. J. Liposome Res., 2009, 19(1), 49-58.
[http://dx.doi.org/10.1080/08982100802564628] [PMID: 19515007]
[40]
Francolini, I.; Giansanti, L.; Piozzi, A.; Altieri, B.; Mauceri, A.; Mancini, G. Glucosylated liposomes as drug delivery systems of usnic acid to address bacterial infections. Colloids Surf. B Biointerfaces, 2019, 181, 632-638.
[http://dx.doi.org/10.1016/j.colsurfb.2019.05.056] [PMID: 31207445]
[41]
Si, K.; Wei, L.; Yu, X.; Wu, F.; Li, X.; Li, C.; Cheng, Y. Effects of (+)-usnic acid and (+)-usnic acid-liposome on Toxoplasma gondii. Exp. Parasitol., 2016, 166, 68-74.
[http://dx.doi.org/10.1016/j.exppara.2016.03.021] [PMID: 27004468]
[42]
Battista, S.; Campitelli, P.; Galantini, L.; Köber, M.; Vargas-Nadal, G.; Ventosa, N.; Giansanti, L. Use of N-oxide and cationic surfactants to enhance antioxidant properties of (+)-usnic acid loaded liposomes. Colloids Surf. A Physicochem. Eng. Asp., 2020, 585, 124154.
[http://dx.doi.org/10.1016/j.colsurfa.2019.124154]
[43]
Arajo, A.A.S.; Nunes, P.S.; Albuquerque-Jnior, R.L.C.; Cavalcante, D.R.R.; Dantas, M.D.M.; Cardoso, J.C.; Bezerra, M.S.; Souza, J.C.C.; Serafini, M.R.; Quitans-Jr, L.J.; Bonjardim, L.R. Collagen-based films containing liposome-loaded usnic acid as dressing for dermal burn healing. J. Biotechnol. Biomed., 2011, 2011
[http://dx.doi.org/ 10.1155/2011/761593]
[44]
Nunes, P.S.; Rabelo, A.S.; Souza, J.C.C.; Santana, B.V.; da Silva, T.M.M.; Serafini, M.R.; dos Passos Menezes, P.; dos Santos Lima, B.; Cardoso, J.C.; Alves, J.C.S.; Frank, L.A.; Guterres, S.S.; Pohlmann, A.R.; Pinheiro, M.S.; de Albuquerque, R.L.C.; Araújo, A.A.S. Gelatin-based membrane containing usnic acid-loaded liposome improves dermal burn healing in a porcine model. Int. J. Pharm., 2016, 513(1-2), 473-482.
[http://dx.doi.org/10.1016/j.ijpharm.2016.09.040] [PMID: 27633280]
[45]
Bangham, A.D.; Standish, M.M.; Watkins, J.C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol., 1965, 13(1), 238-IN27.
[http://dx.doi.org/10.1016/S0022-2836(65)80093-6] [PMID: 5859039]
[46]
Landucci, E.; Bonomolo, F.; De Stefani, C.; Mazzantini, C.; Pellegrini-Giampietro, D.E.; Bilia, A.R.; Bergonzi, M.C. Preparation of liposomal formulations for ocular delivery of thymoquinone: In vitro evaluation in HCEC-2e hconec cells. Pharmaceutics, 2021, 13(12), 2093.
[http://dx.doi.org/10.3390/pharmaceutics13122093] [PMID: 34959374]
[47]
Gonçalves, R.F.S.; Martins, J.T.; Duarte, C.M.M.; Vicente, A.A.; Pinheiro, A.C. Advances in nutraceutical delivery systems: From formulation design for bioavailability enhancement to efficacy and safety evaluation. Trends Food Sci. Technol., 2018, 78, 270-291.
[http://dx.doi.org/10.1016/j.tifs.2018.06.011]
[48]
D’Souza, S.S.; DeLuca, P.P. Methods to assess in vitro drug release from injectable polymeric particulate systems. Pharm. Res., 2006, 23(3), 460-474.
[http://dx.doi.org/10.1007/s11095-005-9397-8] [PMID: 16400516]
[49]
Vasarri, M.; Ponti, L.; Degl’Innocenti, D.; Bergonzi, M.C. Usnic acid-loaded polymeric micelles: An optimal migrastatic-acting formulation in human SH-SY5Y neuroblastoma cells. Pharmaceuticals (Basel), 2022, 15(10), 1207.
[http://dx.doi.org/10.3390/ph15101207] [PMID: 36297319]
[50]
Vasarri, M.; Leri, M.; Barletta, E.; Ramazzotti, M.; Marzocchini, R.; Degl’Innocenti, D. Anti-inflammatory properties of the marine plant Posidonia oceanica (L.). Delile. J. Ethnopharmacol., 2020, 247, 112252.
[http://dx.doi.org/10.1016/j.jep.2019.112252] [PMID: 31562953]
[51]
Huang, Z.; Zheng, G.; Tao, J.; Ruan, J. Anti-inflammatory effects and mechanisms of usnic acid. J. Wuhan Univ. Technol.-. Mat. Sci. Edit., 2011, 26(5), 955-959.
[http://dx.doi.org/10.1007/s11595-011-0344-8]
[52]
Fang, C.L.; Wang, Y.; Tsai, K.H.Y.; Chang, H.I. Liposome-encapsulated baicalein suppressed lipogenesis and extracellular matrix formation in hs68 human dermal fibroblasts. Front. Pharmacol., 2018, 9, 155.
[http://dx.doi.org/10.3389/fphar.2018.00155] [PMID: 29559910]
[53]
Juan, C.A.; Pérez de la Lastra, J.M.; Plou, F.J.; Pérez-Lebeña, E. The chemistry of reactive oxygen species (ros) revisited: Outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int. J. Mol. Sci., 2021, 22(9), 4642.
[http://dx.doi.org/10.3390/ijms22094642] [PMID: 33924958]
[54]
Sahu, S.C.; O’Donnell, M.W., Jr; Sprando, R.L. Interactive toxicity of usnic acid and lipopolysaccharides in human liver HepG2 cells. J. Appl. Toxicol., 2012, 32(9), 739-749.
[http://dx.doi.org/10.1002/jat.2768] [PMID: 22777745]
[55]
Popovici, V.; Matei, E.; Cozaru, G.C.; Aschie, M.; Bucur, L.; Rambu, D.; Costache, T.; Cucolea, I.E.; Vochita, G.; Gherghel, D.; Caraiane, A.; Badea, V. Usnic acid and Usnea barbata (L.) F.H. Wigg. Dry extracts promote apoptosis and dna damage in human blood cells through enhancing ROS levels. Antioxidants, 2021, 10(8), 1171.
[http://dx.doi.org/10.3390/antiox10081171] [PMID: 34439420]
[56]
Han, D.; Matsumaru, K.; Rettori, D.; Kaplowitz, N. Usnic acid-induced necrosis of cultured mouse hepatocytes: Inhibition of mitochondrial function and oxidative stress. Biochem. Pharmacol., 2004, 67(3), 439-451.
[http://dx.doi.org/10.1016/j.bcp.2003.09.032] [PMID: 15037196]
[57]
Qi, W.; Lu, C.; Huang, H.; Zhang, W.; Song, S.; Liu, B. (+)-Usnic acid induces ROS-dependent apoptosis via inhibition of mitochondria respiratory chain complexes and NRF2 expression in lung squamous cell carcinoma. Int. J. Mol. Sci., 2020, 21(3), 876.
[http://dx.doi.org/10.3390/ijms21030876] [PMID: 32013250]
[58]
Kumar, K.; Mishra, J.P.N.; Singh, R.P. Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and γ-H2A.X phosphorylation. Chem. Biol. Interact., 2020, 315, 108898.
[http://dx.doi.org/10.1016/j.cbi.2019.108898] [PMID: 31715134]
[59]
Rabelo, T.K.; Zeidán-Chuliá, F.; Vasques, L.M.; dos Santos, J.P.A.; da Rocha, R.F.; Pasquali, M.A.B.; Rybarczyk-Filho, J.L.; Araújo, A.A.S.; Moreira, J.C.F.; Gelain, D.P. Redox characterization of usnic acid and its cytotoxic effect on human neuron-like cells (SH-SY5Y). Toxicol. In Vitro, 2012, 26(2), 304-314.
[http://dx.doi.org/10.1016/j.tiv.2011.12.003] [PMID: 22186154]
[60]
Piazzini, V.; Landucci, E.; Graverini, G.; Pellegrini-Giampietro, D.; Bilia, A.; Bergonzi, M. Stealth and cationic nanoliposomes as drug delivery systems to increase andrographolide BBB permeability. Pharmaceutics, 2018, 10(3), 128.
[http://dx.doi.org/10.3390/pharmaceutics10030128] [PMID: 30104484]
[61]
Casamonti, M.; Piazzini, V.; Bilia, A.R.; Bergonzi, M.C. Evaluation of skin permeability of resveratrol loaded liposomes and nanostructured lipid carriers using a skin mimic artificial membrane (skin-PAMPA). Drug Deliv. Lett., 2019, 9(2), 134-145.
[http://dx.doi.org/10.2174/2210303109666190207152927]
[62]
Barnoud, J.; Rossi, G.; Marrink, S.J.; Monticelli, L. Hydrophobic compounds reshape membrane domains. PLOS Comput. Biol., 2014, 10(10), e1003873.
[http://dx.doi.org/10.1371/journal.pcbi.1003873] [PMID: 25299598]
[63]
Hoa, N.T.; Van Bay, M.; Mechler, A.; Vo, Q.V. Is usnic acid a promising radical scavenger? ACS Omega, 2020, 5(28), 17715-17720.
[http://dx.doi.org/10.1021/acsomega.0c02306] [PMID: 32715258]