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NAPI"],"award-info":[{"award-number":["#295910 NAPI"]}]},{"name":"JPND","award":["#327571 PETABC"],"award-info":[{"award-number":["#327571 PETABC"]}]},{"name":"JPND","award":["NFR #327571\u2014Norway"],"award-info":[{"award-number":["NFR #327571\u2014Norway"]}]},{"name":"JPND","award":["FFG #882717\u2014Austria"],"award-info":[{"award-number":["FFG #882717\u2014Austria"]}]},{"name":"JPND","award":["BMBF #01ED2106\u2014Germany"],"award-info":[{"award-number":["BMBF #01ED2106\u2014Germany"]}]},{"name":"JPND","award":["MSMT #8F21002\u2014Czech Republic"],"award-info":[{"award-number":["MSMT #8F21002\u2014Czech Republic"]}]},{"name":"JPND","award":["#ES RTD\/2020\/26\u2014Latvia"],"award-info":[{"award-number":["#ES RTD\/2020\/26\u2014Latvia"]}]},{"name":"JPND","award":["ANR #20-JPW2-0002-04\u2014France"],"award-info":[{"award-number":["ANR #20-JPW2-0002-04\u2014France"]}]},{"name":"JPND","award":["SRC #2020-02905\u2014Sweden"],"award-info":[{"award-number":["SRC #2020-02905\u2014Sweden"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypericum perforatum (St. John\u2019s wort) has been described to be beneficial for the treatment of Alzheimer\u2019s disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral \u03b2-amyloid (A\u03b2) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble A\u03b2 were analyzed using biochemical analyses. Our study confirms that the scCO2H. perforatum formulation shows better biological activity against A\u03b2-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble A\u03b2 (\u221227% and \u221225%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.<\/jats:p>","DOI":"10.3390\/ijms25021301","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T03:50:22Z","timestamp":1705895422000},"page":"1301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Apolar Extracts of St. John\u2019s Wort Alleviate the Effects of \u03b2-Amyloid Toxicity in Early Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"given":"Ahmed","family":"El Menuawy","sequence":"first","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"},{"name":"Institute for Breeding Research on Horticultural Crops, Julius K\u00fchn Institute (JKI)\u2014Federal Research Centre for Cultivated Plants, Erwin-Baur Stra\u00dfe 27, 06484 Quedlinburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-6564","authenticated-orcid":false,"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Eiriz","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"H\u00e4hnel","sequence":"additional","affiliation":[{"name":"Institute for Breeding Research on Horticultural Crops, Julius K\u00fchn Institute (JKI)\u2014Federal Research Centre for Cultivated Plants, Erwin-Baur Stra\u00dfe 27, 06484 Quedlinburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-7560","authenticated-orcid":false,"given":"Frank","family":"Marthe","sequence":"additional","affiliation":[{"name":"Institute for Breeding Research on Horticultural Crops, Julius K\u00fchn Institute (JKI)\u2014Federal Research Centre for Cultivated Plants, Erwin-Baur Stra\u00dfe 27, 06484 Quedlinburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"M\u00f6hle","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"G\u00f3rska","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Santos-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-863X","authenticated-orcid":false,"given":"Helle","family":"Wangensteen","sequence":"additional","affiliation":[{"name":"Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo (UiO), Sem S\u00e6lands vei 3, 0371 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-4213","authenticated-orcid":false,"given":"Jens","family":"Pahnke","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Research and Neuropathology Lab\/Section of Neuropathology Research, Department of Pathology, Medical Faculty\/KlinMED, University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway"},{"name":"Institute of Nutritional Medicine (INUM) and L\u00fcbeck Institute of Dermatology (LIED), University of L\u00fcbeck (UzL) and University Medical Center Schleswig-Holstein (UKSH), Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"},{"name":"Department of Pharmacology, Faculty of Medicine, University of Latvia, Jelgavas iela 3, 1004 R\u012bga, Latvia"},{"name":"Department of Neurobiology, School of Neuroscience, Biochemistry and Biophysics, The Georg S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e015746","DOI":"10.1136\/bmjopen-2016-015746","article-title":"Signs and symptoms preceding the diagnosis of Alzheimer\u2019s disease: A systematic scoping review of literature from 1937 to 2016","volume":"7","author":"Bature","year":"2017","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_3","first-page":"313","article-title":"The Epidemiology of Alzheimer\u2019s Disease Modifiable Risk Factors and Prevention","volume":"8","author":"Zhang","year":"2021","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.pneurobio.2011.11.008","article-title":"The future of Alzheimer\u2019s disease: The next 10 years","volume":"95","author":"Hampel","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nrd3842-c1","article-title":"Moving towards early clinical trials for amyloid-targeted therapy in Alzheimer\u2019s disease","volume":"12","author":"Aisen","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Down syndrome","volume":"82","author":"Masters","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1523\/JNEUROSCI.1576-23.2023","article-title":"Alzheimer\u2019s Targeted Treatments: Focus on Amyloid and Inflammation","volume":"43","author":"Iwatsubo","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1515\/revneuro-2017-0063","article-title":"Amyloid toxicity in Alzheimer\u2019s disease","volume":"29","author":"Reiss","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"396","DOI":"10.2174\/156720508785132262","article-title":"Clinico-pathologic function of cerebral ABC transporters-implications for the pathogenesis of Alzheimer\u2019s disease","volume":"5","author":"Pahnke","year":"2008","journal-title":"Curr. Alzheimer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3233\/JAD-2010-1221","article-title":"Alzheimer\u2019s disease and the amyloid-beta peptide","volume":"19","author":"Murphy","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_11","first-page":"362","article-title":"Lecanemab: Appropriate Use Recommendations","volume":"10","author":"Cummings","year":"2023","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_12","first-page":"255","article-title":"Clinical Development of Aducanumab, an Anti-Abeta Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer\u2019s Disease","volume":"4","author":"Chiao","year":"2017","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.5582\/ddt.2021.01061","article-title":"Aducanumab: The first targeted Alzheimer\u2019s therapy","volume":"15","author":"Yang","year":"2021","journal-title":"Drug Discov. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5481","DOI":"10.1038\/s41380-021-01249-0","article-title":"The Amyloid-Beta Pathway in Alzheimer\u2019s Disease","volume":"26","author":"Hampel","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/978-94-007-5416-4_14","article-title":"Alzheimer\u2019s disease","volume":"65","author":"Radanovic","year":"2012","journal-title":"Subcell. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jalz.2018.08.005","article-title":"Understanding disease progression and improving Alzheimer\u2019s disease clinical trials: Recent highlights from the Alzheimer\u2019s Disease Neuroimaging Initiative","volume":"15","author":"Veitch","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1007\/s12035-015-9388-7","article-title":"Multiple Effect of APOE Genotype on Clinical and Neuroimaging Biomarkers Across Alzheimer\u2019s Disease Spectrum","volume":"53","author":"Liu","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Miculas, D.C., Negru, P.A., Bungau, S.G., Behl, T., Hassan, S.S.U., and Tit, D.M. (2022). Pharmacotherapy Evolution in Alzheimer\u2019s Disease: Current Framework and Relevant Directions. Cells, 12.","DOI":"10.3390\/cells12010131"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"870517","DOI":"10.3389\/fnagi.2022.870517","article-title":"Impact of Anti-Amyloid-Beta Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer\u2019s Disease: A Focus on Aducanumab and Lecanemab","volume":"14","author":"Shi","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"New Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2092","DOI":"10.1212\/WNL.0000000000201019","article-title":"Incidence of Amyloid-Related Imaging Abnormalities in Patients with Alzheimer Disease Treated with Anti-Beta-Amyloid Immunotherapy: A Meta-Analysis","volume":"99","author":"Jeong","year":"2022","journal-title":"Neurology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jalz.2011.05.2351","article-title":"Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer\u2019s Association Research Roundtable Workgroup","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"799","DOI":"10.3233\/JAD-230040","article-title":"Playing Russian Roulette with Alzheimer\u2019s Disease Patients: Do the Cognitive Benefits of Lecanemab Outweigh the Risk of Edema, Stroke and Encephalitis?","volume":"92","author":"Atwood","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref_24","unstructured":"Hegrand, M., and Pahnke, J. (2021). [Approval first, research afterwards?]. Tidsskr. Nor Laegeforen., 141."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.nbd.2014.04.001","article-title":"Alzheimer\u2019s and ABC transporters--new opportunities for diagnostics and treatment","volume":"72 Pt A","author":"Pahnke","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.neubiorev.2009.05.006","article-title":"Alzheimer\u2019s disease and blood-brain barrier function-Why have anti-beta-amyloid therapies failed to prevent dementia progression?","volume":"33","author":"Pahnke","year":"2009","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-pharmtox-011613-135959","article-title":"Targeting multidrug resistance protein 1 (MRP1, ABCC1): Past, present, and future","volume":"54","author":"Cole","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2174\/15672050113106660171","article-title":"Reduced Alzheimer\u2019s disease pathology by St. John\u2019s Wort treatment is independent of hyperforin and facilitated by ABCC1 and microglia activation in mice","volume":"10","author":"Hofrichter","year":"2013","journal-title":"Curr. Alzheimer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1172\/JCI57867","article-title":"Cerebral amyloid-beta proteostasis is regulated by the membrane transport protein ABCC1 in mice","volume":"121","author":"Krohn","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.arcmed.2014.10.010","article-title":"Cerebral ABC transporter-common mechanisms may modulate neurodegenerative diseases and depression in elderly subjects","volume":"45","author":"Pahnke","year":"2014","journal-title":"Arch. Med. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jad.2016.12.048","article-title":"Clinical use of Hypericum perforatum (St John\u2019s wort) in depression: A meta-analysis","volume":"210","author":"Ng","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_32","first-page":"166","article-title":"John\u2019s wort\u2014Ancient herbal protector","volume":"32","author":"Hobbs","year":"1990","journal-title":"Pharm. Hist."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11438","DOI":"10.1039\/D1SC03356E","article-title":"Unprecedented polycyclic polyprenylated acylphloroglucinols with anti-Alzheimer\u2019s activity from St. John\u2019s wort","volume":"12","author":"Guo","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3390\/medicines2030251","article-title":"Modes of Action of Herbal Medicines and Plant Secondary Metabolites","volume":"2","author":"Wink","year":"2015","journal-title":"Medicines"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/bpa.12069","article-title":"John\u2019s Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer\u2019s disease mouse model-role of P-glycoprotein","volume":"24","author":"Brenn","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1515\/REVNEURO.2010.21.1.29","article-title":"ABC transporters and drug efflux at the blood-brain barrier","volume":"21","author":"Shen","year":"2010","journal-title":"Rev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/nprot.2009.237","article-title":"NMR-based metabolomic analysis of plants","volume":"5","author":"Kim","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0731-7085(02)00279-0","article-title":"NMR spectroscopy: A useful tool for characterisation of plant extracts, the case of supercritical CO2 arnica extract","volume":"30","author":"Bilia","year":"2002","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bascunana, P., Brackhan, M., Mohle, L., Wu, J., Bruning, T., Eiriz, I., Jansone, B., and Pahnke, J. (2023). Time- and Sex-Dependent Effects of Fingolimod Treatment in a Mouse Model of Alzheimer\u2019s Disease. Biomolecules, 13.","DOI":"10.3390\/biom13020331"},{"key":"ref_40","first-page":"663","article-title":"Influence of hyperforin on the morphology of internal organs and biochemical parameters, in experimental model in mice","volume":"57","author":"Negres","year":"2016","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1016\/j.phytochem.2006.09.018","article-title":"Hyperforin and its analogues inhibit CYP3A4 enzyme activity","volume":"67","author":"Lee","year":"2006","journal-title":"Phytochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.phytochem.2006.11.026","article-title":"Identification of the major constituents of Hypericum perforatum by LC\/SPE\/NMR and\/or LC\/MS","volume":"68","author":"Tatsis","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bse.2017.06.004","article-title":"Comparison of chemical composition of Hypericum perforatum and H. maculatum in Estonia","volume":"73","author":"Rusalepp","year":"2017","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1211\/0022357011775910","article-title":"St John\u2019s wort (Hypericum perforatum L.): A review of its chemistry, pharmacology and clinical properties","volume":"53","author":"Barnes","year":"2001","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_45","first-page":"54","article-title":"Laif 900 in treatment of depression. Proven reliability in first line therapy","volume":"152","author":"Muller","year":"2010","journal-title":"MMW Fortschr. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF02850158","article-title":"Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: A double-blind, randomized, placebo-controlled clinical trial","volume":"21","author":"Uebelhack","year":"2004","journal-title":"Adv. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.maturitas.2014.05.009","article-title":"Depression and dementia: Cause, consequence or coincidence?","volume":"79","author":"Bennett","year":"2014","journal-title":"Maturitas"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/YCO.0b013e32834bb9d4","article-title":"Depression in dementia: Epidemiology, mechanisms, and treatment","volume":"24","author":"Enache","year":"2011","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.3389\/fpls.2016.01004","article-title":"Neuroprotective Activity of Hypericum perforatum and Its Major Components","volume":"7","author":"Oliveira","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1055\/s-2006-931567","article-title":"Multivariate analysis of integrated and full-resolution 1H-NMR spectral data from complex pharmaceutical preparations: St. John\u2019s wort","volume":"72","author":"Rasmussen","year":"2006","journal-title":"Planta Med."},{"key":"ref_51","first-page":"277","article-title":"Long-term effects of St. John\u2019s wort (Hypericum perforatum) treatment: A 1-year safety study in mild to moderate depression","volume":"16","author":"Brattstrom","year":"2009","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1017\/S1041610292000930","article-title":"Nutritional patterns and weight change in Alzheimer patients","volume":"4","author":"Silverstone","year":"1992","journal-title":"Int. Psychogeriatr.\/IPA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1177\/002383099300600106","article-title":"Weight loss in Alzheimer\u2019s disease","volume":"6","author":"Du","year":"1993","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chen, S., Sarasua, S.M., Davis, N.J., DeLuca, J.M., Thielke, S.M., and Yu, C.E. (2023). Weight Loss Is a Strong Predictor of Memory Disorder Independent of Genetic Influences. Genes, 14.","DOI":"10.3390\/genes14081563"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00228-006-0096-0","article-title":"Hyperforin in St. John\u2019s wort drug interactions","volume":"62","author":"Madabushi","year":"2006","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00210-007-0172-8","article-title":"Variability in PXR-mediated induction of CYP3A4 by commercial preparations and dry extracts of St. John\u2019s wort","volume":"375","author":"Metzger","year":"2007","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_57","unstructured":"Kuhn, J., and Sharman, T. (2023). StatPearls [Internet], StatPearls Publishing."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1073\/pnas.93.7.2996","article-title":"Enhanced pathologic properties of Dutch-type mutant amyloid beta-protein","volume":"93","author":"Davis","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mohle, L., Stefan, K., Bascunana, P., Brackhan, M., Bruning, T., Eiriz, I., El Menuawy, A., van Genderen, S., Santos-Garcia, I., and Gorska, A.M. (2023). ABC Transporter C1 Prevents Dimethyl Fumarate from Targeting Alzheimer\u2019s Disease. Biology, 12.","DOI":"10.3390\/biology12070932"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"147579","DOI":"10.1016\/j.brainres.2021.147579","article-title":"Dimethyl fumarate does not mitigate cognitive decline and beta-amyloidosis in female APPPS1 mice","volume":"1768","author":"Mohle","year":"2021","journal-title":"Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/sj.embor.7400784","article-title":"Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology","volume":"7","author":"Radde","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2174\/156720511797633179","article-title":"Determination of spatial and temporal distribution of microglia by 230 nm-high-resolution, high-throughput automated analysis reveals different amyloid plaque populations in an APP\/PS1 mouse model of Alzheimer\u2019s disease","volume":"8","author":"Scheffler","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.3762\/bjnano.10.162","article-title":"Nanoporous smartPearls for dermal application-Identification of optimal silica types and a scalable production process as prerequisites for marketed products","volume":"10","author":"Hespeler","year":"2019","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Perez-Roman, I., Kiekens, F., Cordoba-Diaz, D., Garcia-Rodriguez, J.J., and Cordoba-Diaz, M. (2020). Development of a Solid Formulation Containing a Microemulsion of a Novel Artemisia Extract with Nematocidal Activity for Oral Administration. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090873"},{"key":"ref_65","first-page":"61","article-title":"Comparative evaluation of porous silica based carriers for lipids and liquid drug formulations","volume":"1","author":"Choudhari","year":"2014","journal-title":"Open Mater. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1093\/hmg\/ddaa179","article-title":"Gene therapy for Alzheimer\u2019s disease targeting CD33 reduces amyloid beta accumulation and neuroinflammation","volume":"29","author":"Griciuc","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1074\/jbc.RA118.006379","article-title":"Reduction of the expression of the late-onset Alzheimer\u2019s disease (AD) risk-factor BIN1 does not affect amyloid pathology in an AD mouse model","volume":"294","author":"Andrew","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13024-022-00547-7","article-title":"Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia","volume":"17","author":"Xia","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_69","first-page":"21","article-title":"Power comparisons of shapiro-wilk, kolmogorov-smirnov, lilliefors and anderson-darling tests","volume":"2","author":"Razali","year":"2011","journal-title":"J. Stat. Model. Anal."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:35Z","timestamp":1760103995000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/1301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,21]]},"references-count":69,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25021301"],"URL":"https:\/\/doi.org\/10.3390\/ijms25021301","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,21]]}}}