{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:47:19Z","timestamp":1792806439238,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017266","name":"Government of Navarra","doi-asserted-by":"publisher","award":["PI045, PI068"],"award-info":[{"award-number":["PI045, PI068"]}],"id":[{"id":"10.13039\/501100017266","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tropical Health Institute, University of Navarra and funders","award":["XX"],"award-info":[{"award-number":["XX"]}],"id":[{"id":"https:\/\/ror.org\/02rxc7m23","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Berberine (BER)\u2014an anti-inflammatory quaternary isoquinoline alkaloid extracted from plants\u2014has been reported to have a variety of biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded liposomes with the aim to prevent its rapid liver metabolism and improve the drug selective delivery to the infected organs in visceral leishmaniasis (VL). BER liposomes (LP-BER) displayed a mean size of 120 nm, negative Z-potential of \u221238 mV and loaded 6 nmol\/\u03bcmol lipid. In vitro, the loading of BER in liposomes enhanced its selectivity index more than 7-fold by decreasing its cytotoxicity to macrophages. In mice, LP-BER enhanced drug accumulation in the liver and the spleen. Consequently, the liposomal delivery of the drug reduced parasite burden in the liver and spleen by three and one logarithms (99.2 and 93.5%), whereas the free drug only decreased the infection in the liver by 1-log. The organ drug concentrations\u2014far from IC50 values\u2014 indicate that BER immunomodulatory activity or drug metabolites also contribute to the efficacy. Although LP-BER decreased 10-fold\u2014an extremely rapid clearance of the free drug in mice\u2014the value remains very high. Moreover, LP-BER reduced plasma triglycerides levels.<\/jats:p>","DOI":"10.3390\/pharmaceutics12090858","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T22:58:01Z","timestamp":1599778681000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Berberine-Loaded Liposomes for the Treatment of Leishmania infantum-Infected BALB\/c Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4249-9204","authenticated-orcid":false,"given":"Alba","family":"Calvo","sequence":"first","affiliation":[{"name":"ISTUN Institute of Tropical Health, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"Chemistry and Pharmaceutical Technology Department, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Moreno","sequence":"additional","affiliation":[{"name":"ISTUN Institute of Tropical Health, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"Chemistry and Pharmaceutical Technology Department, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"IdisNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1443-6513","authenticated-orcid":false,"given":"Esther","family":"Larrea","sequence":"additional","affiliation":[{"name":"ISTUN Institute of Tropical Health, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"IdisNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3431-7826","authenticated-orcid":false,"given":"Carmen","family":"Sanmart\u00edn","sequence":"additional","affiliation":[{"name":"ISTUN Institute of Tropical Health, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"Chemistry and Pharmaceutical Technology Department, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"IdisNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9687-3436","authenticated-orcid":false,"given":"Juan Manuel","family":"Irache","sequence":"additional","affiliation":[{"name":"Chemistry and Pharmaceutical Technology Department, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"IdisNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Socorro","family":"Espuelas","sequence":"additional","affiliation":[{"name":"ISTUN Institute of Tropical Health, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"Chemistry and Pharmaceutical Technology Department, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain"},{"name":"IdisNA, Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alvar, J., Velez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., and Boer, M.D. (2012). Leishmaniasis Worldwide and Global Estimates of Its Incidence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035671"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ponte-Sucre, A., Gamarro, F., Dujardin, J.-C., Barrett, M.P., Lopez-V\u00e9lez, R., Garc\u00eda-Hern\u00e1ndez, R., Pountain, A.W., Mwenechanya, R., and Papadopoulou, B. (2017). Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. Plos Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006052"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1517\/13543776.2013.746314","article-title":"Berberine and its derivatives: A patent review (2009\u20132012)","volume":"23","author":"Singh","year":"2012","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/ptr.5693","article-title":"Berberis Vulgarisand Berberine: An Update Review","volume":"30","author":"Imenshahidi","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_6","first-page":"29","article-title":"Cutaneous leishmaniasis in domestic dogs","volume":"37","author":"Ahuja","year":"1993","journal-title":"Indian J. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1007\/s00436-013-3727-2","article-title":"Effect of root bark extract of Berberis vulgaris L. on Leishmania major on BALB\/c mice","volume":"113","author":"Salehabadi","year":"2013","journal-title":"Parasitol. Res."},{"key":"ref_8","first-page":"28","article-title":"In Vitro Inhibitory Effect of Berberis vulgaris (Berberidaceae) and Its Main Component, Berberine against Different Leishmania Species","volume":"9","author":"Mahmoudvand","year":"2014","journal-title":"Iran. J. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Saha, P., Bhattacharjee, S., Sarkar, A., Manna, A., Majumder, S., and Chatterjee, M. (2011). Berberine Chloride Mediates Its Anti-Leishmanial Activity via Differential Regulation of the Mitogen Activated Protein Kinase Pathway in Macrophages. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018467"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1080\/10715760903186124","article-title":"Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes","volume":"43","author":"Saha","year":"2009","journal-title":"Free. Radic. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/0014-4894(85)90047-5","article-title":"Leishmania donovani: Amastigote inhibition and mode of actior of berberine","volume":"60","author":"Ghosh","year":"1985","journal-title":"Exp. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1128\/AAC.34.5.918","article-title":"Berberine derivatives as antileishmanial drugs","volume":"34","author":"Vennerstrom","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.2217\/nnm-2018-0097","article-title":"Dual-targeted nano-in-nano albumin carriers enhance the efficacy of combined chemo\/herbal therapy of lung cancer","volume":"13","author":"Elgohary","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s13346-018-0485-9","article-title":"Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors","volume":"8","author":"Bhatnagar","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3109\/03639045.2012.683875","article-title":"Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride","volume":"39","author":"Zhu","year":"2012","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12951-018-0402-x","article-title":"Self-nanoemulsifying system improves oral absorption and enhances anti-acute myeloid leukemia activity of berberine","volume":"16","author":"Li","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-09852-0","article-title":"Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases","volume":"10","author":"Guo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jconrel.2016.12.042","article-title":"Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction","volume":"247","author":"Allijn","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5049","DOI":"10.2147\/IJN.S84565","article-title":"Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db\/db mice","volume":"10","author":"Xue","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.biopha.2018.05.067","article-title":"Nano strategies for berberine delivery, a natural alkaloid of Berberis","volume":"104","author":"Mirhadi","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Saleem, K., Khursheed, Z., Hano, C., Anjum, I., and Anjum, S. (2019). Applications of Nanomaterials in Leishmaniasis: A Focus on Recent Advances and Challenges. Nanomaterials, 9.","DOI":"10.3390\/nano9121749"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.biopha.2018.05.004","article-title":"Pharmacokinetic of meglumine antimoniate encapsulated in phosphatidylserine-liposomes in mice model: A candidate formulation for visceral leishmaniasis","volume":"103","author":"Borborema","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Burza, S., Sinha, P.K., Mahajan, R., Lima, M.A., Mitra, G., Verma, N., Balasegarem, M., and Das, P. (2014). Five-Year Field Results and Long-Term Effectiveness of 20 mg\/kg Liposomal Amphotericin B (Ambisome) for Visceral Leishmaniasis in Bihar, India. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002603"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00962-17","DOI":"10.1128\/AAC.00962-17","article-title":"Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB\/c Mice","volume":"61","author":"Reis","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1016\/j.nano.2015.06.008","article-title":"Targeted delivery of paromomycin in murine infectious diseases through association to nano lipid systems","volume":"11","author":"Gaspar","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Osada, Y., Omachi, S., Sanjoba, C., Matsumoto, Y., Noiri, E., and Jha, T. (2016). Animal Models of Visceral Leishmaniasis and Applicability to Disease Control. Kala Azar in South Asia, Springer Science and Business Media LLC.","DOI":"10.1007\/978-3-319-47101-3_23"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-4939-6591-5_2","article-title":"Thin-Film Hydration Followed by Extrusion Method for Liposome Preparation","volume":"1522","author":"Zhang","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1007\/BF02531316","article-title":"Two dimensional thin layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots","volume":"5","author":"Rouser","year":"1970","journal-title":"Lipids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1093\/jac\/dkv237","article-title":"Lack of correlation between the promastigote back-transformation assay and miltefosine treatment outcome","volume":"70","author":"Hendrickx","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cmpb.2010.01.007","article-title":"PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel","volume":"99","author":"Zhang","year":"2010","journal-title":"Comput. Methods Programs Biomed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/jphp.12692","article-title":"Preparation, pharmacokinetics and tumour-suppressive activity of berberine liposomes","volume":"69","author":"Wang","year":"2017","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_32","unstructured":"(2020, May 20). Charles River. Available online: https:\/\/www.criver.com\/sites\/default\/files\/Technical%20Resources\/Clinical%20Pathology%20Data%20for%20BALB_c%20Mouse%20Colonies%20in%20North%20America%20for%20January%202008%20-%20December%202012.pdf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/ptr.2399","article-title":"Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine","volume":"22","author":"Imanshahidi","year":"2008","journal-title":"Phytother. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1517\/13543776.2016.1118060","article-title":"Pharmacological effects of berberine and its derivatives: A patent update","volume":"26","author":"Jin","year":"2016","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/03602532.2017.1306544","article-title":"The metabolism of berberine and its contribution to the pharmacological effects","volume":"49","author":"Wang","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.fitote.2016.02.001","article-title":"Research progress on berberine with a special focus on its oral bioavailability","volume":"109","author":"Liu","year":"2016","journal-title":"Fitoterapia"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Malebo, H.M., Wenzler, T., Cal, M., Swaleh, S.M., Omolo, M.O., Hassanali, A., S\u00e9quin, U., H\u00e4ussinger, D., Dalsgaard, P.W., and Hamburger, M. (2013). Anti-protozoal activity of aporphine and protoberberine alkaloids from Annickia kummeriae (Engl. & Diels) Setten & Maas (Annonaceae). BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-48"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ijpharm.2018.06.018","article-title":"Promising nanotherapy in treating leishmaniasis","volume":"547","author":"Marins","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jconrel.2011.09.098","article-title":"The journey of a drug-carrier in the body: An anatomo-physiological perspective","volume":"161","author":"Bertrand","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10287","DOI":"10.1073\/pnas.1401337111","article-title":"Engineered nanomedicine for myeloma and bone microenvironment targeting","volume":"111","author":"Swami","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jconrel.2019.09.020","article-title":"Optimizing biodegradable nanoparticle size for tissue-specific delivery","volume":"314","author":"Mandl","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.4049\/jimmunol.181.2.1386","article-title":"Complete cure of experimental visceral leishmaniasis with amphotericin B in stearylamine-bearing cationic liposomes involves down-regulation of IL-10 and favorable T cell responses","volume":"181","author":"Banerjee","year":"2008","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1128\/AAC.00524-10","article-title":"Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation","volume":"55","author":"Banerjee","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1128\/AAC.03305-14","article-title":"Cationic Liposomal Sodium Stibogluconate (SSG), a Potent Therapeutic Tool for Treatment of Infection by SSG-Sensitive and -Resistant Leishmania donovani","volume":"59","author":"Sinha","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","unstructured":"Ahmad, M. (2012). Lipids in Nanotechnology, AOCS Press. [1st ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fmolb.2018.00021","article-title":"Toxicological Effects of Berberine and Sanguinarine","volume":"5","author":"Singh","year":"2018","journal-title":"Front. Mol. Biosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jconrel.2011.12.029","article-title":"The effect of tocopherol on the structure and permeability of phosphatidylcholine liposomes","volume":"160","author":"Quinn","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1021\/np400607k","article-title":"Berberine and Its Metabolites: Relationship between Physicochemical Properties and Plasma Levels after Administration to Human Subjects","volume":"77","author":"Spinozzi","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1208\/s12249-010-9520-y","article-title":"Physicochemical Characterization of Berberine Chloride: A Perspective in the Development of a Solution Dosage Form for Oral Delivery","volume":"11","author":"Battu","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"118456","DOI":"10.1016\/j.ijpharm.2019.118456","article-title":"Therapeutic delivery to the peritoneal lymphatics: Current understanding, potential treatment benefits and future prospects","volume":"567","author":"Sarfarazi","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4987","DOI":"10.1021\/acs.molpharmaceut.9b00855","article-title":"Lymphatic Uptake of Liposomes after Intraperitoneal Administration Primarily Occurs via the Diaphragmatic Lymphatics and is Dependent on Liposome Surface Properties","volume":"16","author":"Lee","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1124\/jpet.115.231043","article-title":"Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages","volume":"358","author":"Shin","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.fct.2010.01.033","article-title":"Acute toxicity of berberine and its correlation with the blood concentration in mice","volume":"48","author":"Kheir","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0021-9673(02)00378-3","article-title":"Simultaneous determination of berberine in rat blood, liver and bile using microdialysis coupled to high-performance liquid chromatography","volume":"961","author":"Tsai","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E955","DOI":"10.1152\/ajpendo.90599.2008","article-title":"Berberine suppresses proinflammatory responses through AMPK activation in macrophages","volume":"296","author":"Jeong","year":"2009","journal-title":"Am. J. Physiol.Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nrendo.2016.210","article-title":"Functional foods and dietary supplements for the management of dyslipidaemia","volume":"13","author":"Hunter","year":"2017","journal-title":"Nat. Rev. Endocrinol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:08:22Z","timestamp":1760177302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,9]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["pharmaceutics12090858"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12090858","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,9]]}}}