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Network Pharmacology Reveals the Therapeutic Potential of BBB-Permeable Compounds from Lonicera caerulea for Alzheimer’s Disease and Lipid Metabolism Disorders

Year: 2026

Type: article

Abstract: Although risk factors for Alzheimer’s 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–brain 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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27104556

Authors: Jiayi He, Jihong Li, Junwei Huo, Yijun Pang, Kaiqi Sun, Haoyu Zhu, Yuhan He, Zhixuan Ren, Xin Cheng, Shuang Ao, Yahui Peng

Institutions: Harbin Medical University, National Development and Reform Commission, Northeast Agricultural University, Ministry of Agriculture and Rural Affairs

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499