{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:53Z","timestamp":1785428093590,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program of Heilongjiang Province","award":["GZ2024021"],"award-info":[{"award-number":["GZ2024021"]}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"crossref","award":["JJ2025XQ0159"],"award-info":[{"award-number":["JJ2025XQ0159"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Project of \u201c14th Five-Year\u201d Plan for Heilongjiang Provincial Educational Science Research","award":["GJB1425362"],"award-info":[{"award-number":["GJB1425362"]}]},{"DOI":"10.13039\/100010722","name":"Harbin Medical University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010722","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05jscf583","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of China","award":["2022YFD1600500"],"award-info":[{"award-number":["2022YFD1600500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although risk factors for Alzheimer\u2019s disease (AD) involve obesity and elevated low-density lipoprotein (LDL) cholesterol levels, and Lonicera caerulea has been reported to improve lipid metabolism disorders (LMDs), it remains unknown whether Lonicera caerulea can simultaneously modulate the progression of both AD and LMDs. In this study, an integrative strategy combining network pharmacology, Mendelian randomization (MR), molecular docking, and molecular dynamics simulations was employed to explore potential targets, pathways, and causal relationships. Network pharmacology and molecular docking results revealed that several blood\u2013brain barrier (BBB)-permeable active components of Lonicera caerulea, including Naringenin and Palmatine, may be associated with targets involved in the lipid and atherosclerosis pathway, such as HSP90AA1, SRC and TNF. These associations indicate a potential link between the modulation of lipid metabolism and AD-related processes, although further validation is required. Molecular dynamics simulations were conducted to support the stability of key docking complexes. Given that elevated LDL is a central feature of LMDs and a key indicator of cholesterol imbalance, MR analysis was conducted to assess its causal relationship with AD. The results provided genetic evidence supporting a causal role of elevated LDL in AD risk, reinforcing the epidemiological link between lipid metabolism and neurodegeneration. These findings imply that BBB-permeable constituents of Lonicera caerulea may exert multi-target effects relevant to AD and LMDs. Enrichment analysis further indicates a possible involvement of pathways associated with lipid and atherosclerosis, supporting its potential as a dietary strategy for at-risk populations.<\/jats:p>","DOI":"10.3390\/ijms27104556","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:53:10Z","timestamp":1779191590000},"page":"4556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology Reveals the Therapeutic Potential of BBB-Permeable Compounds from Lonicera caerulea for Alzheimer\u2019s Disease and Lipid Metabolism Disorders"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6906-7607","authenticated-orcid":false,"given":"Jiayi","family":"He","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-0104","authenticated-orcid":false,"given":"Jihong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"},{"name":"Translational Medicine Center of Northern China, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-8697","authenticated-orcid":false,"given":"Junwei","family":"Huo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Affairs, College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin 150030, China"},{"name":"National-Local Joint Engineering Research Center for Development and Utilization of Small Fruits in Cold Regions, National Development and Reform Commission, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6076-9796","authenticated-orcid":false,"given":"Yahui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150086, China"},{"name":"Translational Medicine Center of Northern China, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102481","DOI":"10.1016\/j.arr.2024.102481","article-title":"Pathogenesis, diagnostics, and therapeutics for Alzheimer\u2019s disease: Breaking the memory barrier","volume":"101","author":"Kamatham","year":"2024","journal-title":"Ageing Res. 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