{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:56:54Z","timestamp":1791601014823,"version":"4.3.4"},"reference-count":155,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404834"],"award-info":[{"award-number":["82404834"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82404834"],"award-info":[{"award-number":["82404834"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Youth Science and Technology Innovation Capacity Cultivation Project of Heilongjiang University of Chinese Medicine","award":["2024XJJ-QNCX022, 2024KYYWF-1391"],"award-info":[{"award-number":["2024XJJ-QNCX022, 2024KYYWF-1391"]}]},{"award":["2024XJJ-QNCX022, 2024KYYWF-1391"],"award-info":[{"award-number":["2024XJJ-QNCX022, 2024KYYWF-1391"]}],"id":[{"id":"https:\/\/ror.org\/05x1ptx12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Heilongjiang Chunyan Innovation Team Program","award":["CYQN24014"],"award-info":[{"award-number":["CYQN24014"]}]},{"name":"Heilongjiang Provincial Natural Science Foundation Team Project","award":["TD2024H002"],"award-info":[{"award-number":["TD2024H002"]}]},{"name":"Heilongjiang Province \"Double First-Class\" Discipline Collaborative Innovation Achievements Construction Project","award":["LJGXCG2022-096"],"award-info":[{"award-number":["LJGXCG2022-096"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex, multifactorial neurodegenerative disorder whose core pathological hallmarks include A\u03b2 aggregation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota dysbiosis. Lignans, a class of naturally occurring polyphenolic dimers widely distributed in medicinal plants and diet, exhibit multi-target neuroprotective effects with low toxicity. This review provides a systematic synthesis of the anti-AD pharmacological mechanisms underlying nine structurally distinct lignan subtypes\u2014dibenzocyclooctadiene, tetrahydrofuran, bisepoxy, benzofuran, and biphenyl types\u2014emphasizing scaffold-dependent structure\u2013activity relationships. Key mechanistic pathways encompass direct inhibition of A\u03b2 aggregation and tau phosphorylation, activation of the Nrf2 antioxidant signaling axis and PI3K\/Akt pro-survival pathways, suppression of NF-\u03baB-mediated neuroinflammation, restoration of cholinergic function, protection of mitochondria via SIRT3, inhibition of ferroptosis through Gsk3\u03b2\/Nrf2\/GPX4 signaling, and modulation of the gut\u2013brain axis via microbiota-mediated conversion to enterolactone. This review addresses key pharmacokinetic limitations such as low oral bioavailability, rapid metabolism, and limited brain exposure, alongside strategies including structural modification, brain-targeted delivery systems, and gut microbiota modulation. Despite promising preclinical evidence, clinical translation remains limited. Future research priorities should focus on direct target validation, network pharmacology, optimized formulations, and well-designed clinical trials to develop lignans into next-generation anti-aging and anti-AD therapeutics.<\/jats:p>","DOI":"10.3390\/molecules31152594","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological Effects and Molecular Mechanisms of Lignans in the Treatment of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"31","author":[{"given":"Limeng","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China"},{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China"},{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China"},{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China"},{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"},{"name":"College of Agriculture, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhang","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"},{"name":"College of Agriculture, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China"},{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China"},{"name":"Traditional Chinese Medicine Biological Genetics, Heilongjiang Province Double First-Class Construction Interdiscipline, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). 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